Chemical Constituents from <i>Croton</i> Species and Their Biological Activities.

Xu WH; Liu WY; Liang Q

doi:10.3390/molecules23092333

Chemical Constituents from Croton Species and Their Biological Activities.

Xu WH ¹,

Liu WY ¹,

Liang Q ¹

Affiliations

1. Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China.
Authors
Xu WH¹
Liu WY¹
Liang Q¹
(3 authors)

ORCIDs linked to this article

Xu WH | 0000-0002-9490-0207

Molecules (Basel, Switzerland), 12 Sep 2018, 23(9):E2333
https://doi.org/10.3390/molecules23092333 PMID: 30213129 PMCID: PMC6225158

Review

This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.

Free full text in Europe PMC

Abstract

The genus Croton belongs to the Euphorbiaceae family, which comprises approximately 1300 species. Many Croton species have been used as folk medicines. This review focuses on the chemical constituents from Croton species and their relevant biological activities, covering the period from 2006 to 2018. A total of 399 new compounds, including 339 diterpenoids, were reported. Diterpenoids are characteristic components of the Croton species. These isolated compounds exhibited a broad spectrum of bioactivities, including cytotoxic, anti-inflammatory, antifungal, acetylcholinesterase inhibitory, and neurite outgrowth-promoting properties. The present review provides a significant clue for further research of the chemical constituents from the Croton species as potential medicines.

Free full text

Molecules. 2018 Sep; 23(9): 2333.

Published online 2018 Sep 12. https://doi.org/10.3390/molecules23092333

PMCID: PMC6225158

PMID: 30213129

Chemical Constituents from Croton Species and Their Biological Activities

Wen-Hui Xu, Wei-Yi Liu, and Qian Liang^*

Author information Article notes Copyright and License information Disclaimer

This article has been cited by other articles in PMC.

Go to:

Abstract

Keywords: Croton species, phytochemistry, biological activities, diterpenoids, cytotoxicity

Go to:

1. Introduction

The genus Croton belongs to the Euphorbiaceae family, and contains approximately 1300 species of trees, shrubs, and herbs, which are widely distributed throughout tropical and subtropical regions of the world. Many Croton species have been used as folk medicines in Africa, south Asia, and south America, for the treatment of many diseases such as stomachache, abscesses, inflammation, and malaria [1,2,3]. The seeds of C. tiglium, which are well-known as “badou”, had been utilized as a traditional Chinese medicine to treat gastrointestinal disorders, intestinal inflammation, and rheumatism. The roots of C. crassifolius, known as “jiguxiang” in China, are mainly used as a traditional medicine for the treatment of stomachache and sore throat [3]. The genus Croton is abundant in diverse diterpenoids, including clerodane, tigliane, kaurane, labdane, cembrane, and pimarane, with a wide range of biological activities, such as cytotoxic, anti-inflammatory, and anti-microbial [1,2,3,4,5]. Due to their great structural diversity and broad relevant bioactivities, Croton species have attracted increasing research attention. Several authors have provided reviews about the chemical constituents and biological activities of Croton species. A review came out in 2006 regarding clerodane diterpenes isolated from Croton species, their ¹³C-NMR spectroscopic data, and biological activities [2]. In 2007, a comprehensive review on the traditional uses, chemistry, and pharmacology of Croton species was published [1]. In 2013, anticancer and antioxidant activities of extracts and pure compounds from several Croton species were reviewed [4]. Five review articles were published in recent years which focused on ethnopharmacological uses, phytochemistry, and pharmacology of a single Croton species [6,7,8,9,10]. In the last decade, there has been a dramatic progress in the chemical constituents and relevant biological activities of Croton species. However, so far, no comprehensive review has been published since 2007. In the present review, we summarize systematically the research advances on the new chemical constituents and their biological activities of Croton species reported in the literature, as found on Web of Science, Google Scholar, PubMed, and SciFinder, from 2006 to March 2018, with the aim of providing a basis for further research of natural product drug discovery.

Go to:

2. Chemical Constituents

To date, 399 new compounds have been isolated and identified from Croton species, including 339 diterpenoids (1–339), seven sesquiterpenoids (340–346), one sesterterpenoid (347), one triterpenoid (348), 21 glycosides (349–369), eight alkaloids (370–377), three benzoate derivatives (378–380), three pyran-2-one derivatives (381–383), two cyclopeptide (384, 385), two tropone derivatives (386, 387), two limonoids (388, 389), and ten miscellaneous compounds (390–399). Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12 and Figure 13 and Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16, Table 17, Table 18, Table 19, Table 20, Table 21, Table 22, Table 23, Table 24, Table 25, Table 26 and Table 27.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g001a.jpg

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g001b.jpg

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g001c.jpg

Figure 1

Clerodane type diterpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g002a.jpg

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g002b.jpg

Figure 2

Tigliane type diterpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g003.jpg

Figure 3

Kaurane type diterpenoids from the genus Croton 1.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g004.jpg

Figure 4

Crotofolane type diterpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g005.jpg

Figure 5

Labdane type diterpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g006.jpg

Figure 6

Cembrane type diterpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g007.jpg

Figure 7

Abietane type diterpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g008.jpg

Figure 8

Casbane, Halimane, Pimarane and Cleistanthane type diterpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g009.jpg

Figure 9

Grayanane, Atisane, Phytane, Laevinane type diterpenoids and Meroditerpenoids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g010.jpg

Figure 10

Sesquiterpenoids, Sesterterpenoid and Triterpenoid from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g011.jpg

Figure 11

Glycosides from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g012.jpg

Figure 12

Alkaloids from the genus Croton.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g013.jpg

Figure 13

Miscellaneous compounds from the genus Croton.

Table 1

Clerodane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
1	ent-3,13E-clerodadiene-15-formate	C₂₁H₃₄O₂	C. sylvaticus	[12]
2	9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic acid	C₂₀H₂₈O₄	C. crassifolius	[14]
3	9-[2-(2(5H)-furanone-4-yl)ethyl]-4,8,9-trimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-4-carboxylic ester	C₂₁H₃₀O₄	C. crassifolius	[14]
4	Centrafricine I	C₂₁H₂₄O₆	C. mayumbensis	[19]
5	Marrubiagenin	C₂₀H₂₈O₄	C. glabellus	[15]
6	Methyl 15,16-epoxy-3,13(16),14-ent-clerodatrien-18,19-olide-17-carboxylate	C₂₁H₂₆O₅	C. oblongifolius	[29]
7	Dimethyl 15,16-epoxy-12-oxo-3,13(16),14-ent-clerodatriene-17,18-dicarboxylate	C₂₂H₂₈O₆	C. oblongifolius	[29]
8	Isoteucvin	C₁₉H₂₀O₅	C. jatrophoides	[30]
9	Jatrophoidin	C₂₁H₂₂O₇	C. jatrophoides	[30]
10	8-Epicordatin	C₂₁H₂₆O₆	C. palanostigma	[31]
11	laevigatbenzoate	C₂₇H₃₁O₅	C. laevigatus	[13]
12	3,4,15,16-diepoxy-cleroda-13(16),14-diene-12,17-olide	C₂₀H₂₆O₄	C. oblongifolius	[22]
13	Crassifolin A	C₂₁H₃₀O₄	C. crassifolius	[16]
14	Crassifolin B	C₂₀H₂₉O₄	C. crassifolius	[16]
15	Crassifolin C	C₂₁H₂₄O₅	C. crassifolius	[16]
16	Crassifolin D	C₂₁H₂₄O₆	C. crassifolius	[16]
17	Crassifolin E	C₂₀H₂₃O₆	C. crassifolius	[16]
18	Crassifolin F	C₂₃H₂₉O₇	C. crassifolius	[16]
19	Crassifolin G	C₁₉H₂₀O₆	C. crassifolius	[16]
20	Methyl 3-oxo-12-epibarbascoate	C₂₁H₂₆O₆	C. urucurana	[32]
21	Laevinoids A	C₂₀H₂₂O₅	C. laevigatus	[20]
22	Laevinoids B	C₂₀H₂₃O₅Cl	C. laevigatus	[20]
23	Crotonolide A	C₂₀H₁₈O₆	C. laui	[21]
24	Crotonolide B	C₂₁H₂₄O₆	C. laui	[21]
25	Isocrotonolide B	C₂₁H₂₄O₆	C. laui	[21]
26	Crotonolide C	C₂₃H₂₆O₈	C. laui	[21]
27	Isocrotonolide C	C₂₃H₂₆O₈	C. laui	[21]
28	Crotonolide D	C₂₁H₂₆O₆	C. laui	[21]
29	Isocrotonolide D	C₂₁H₂₆O₆	C. laui	[21]
30	Crotonolide E	C₂₀H₂₆O₄	C. laui	[21]
31	Crotonolide F	C₂₀H₂₆O₄	C. laui	[21]
32	Crotonolide G	C₂₀H₃₂O	C. laui	[21]
33	Crotonolide H	C₂₀H₃₂O₄	C. laui	[21]
34	12-Deoxycrotonolide H	C₂₀H₃₂O₃	C. laui	[21]
35	Crotonoligaketone	C₂₃H₂₆O₈	C. oligandrum	[33]
36	Crotonpene A	C₂₀H₂₆O₃	C. yanhuii	[23]
37	Crotonpene B	C₂₁H₂₈O₅	C. yanhuii	[23]
38	Crassifolin I	C₂₀H₂₂O₆	C. crassifolius	[34]
39	Crassifolin H	C₁₉H₂₀O₅	C. crassifolius	[34]
40	Crotoeurin A	C₃₈H₃₆O₁	C. euryphyllus	[25]
41	Crotoeurin B	C₂₀H₂₄O₆	C. euryphyllus	[25]
42	Crotoeurin C	C₂₀H₂₂O₆	C. euryphyllus	[25]
43	3-Oxo-15,16-epoxy-4α,12-dihydroxy-ent-neo-clerodan-13(16),14-diene	C₂₀H₃₀O₄	C. limae	[35]
44	15,16-Epoxy-3α,4α,12-trihydroxy-ent-neo-clerodan- 13(16),14-diene	C₂₀H₃₂O₄	C. limae	[35]
45	3α,4α,15,16-Tetrahydroxy-ent-neo-cleroda-13E-ene	C₂₀H₃₆O₄	C. limae	[35]
46	Cracroson A	C₁₉H₂₁O₆	C. crassifolius	[26]
47	Cracroson B	C₂₀H₂₂O₆	C. crassifolius	[26]
48	Cracroson C	C₁₉H₁₉O₄N	C. crassifolius	[26]
49	Crassifolin J	C₂₀H₂₀O₅	C. crassifolius	[36]
60	Crotocorylifuran-2-one	C₂₂H₂₄O₈	C.megalocarpoides	[27]
61	Megalocarpoidolide D	C₂₂H₂₂O₈	C.megalocarpoides	[27]
62	7,8-Dehydrocrotocorylifuran	C₂₂H₂₄O₇	C.megalocarpoides	[27]
63	Megalocarpoidolide E	C₂₂H₂₄O₈	C.megalocarpoides	[27]
64	Megalocarpoidolide F	C₂₂H₂₄O₈	C.megalocarpoides	[27]
65	Megalocarpoidolide G	C₂₂H₂₄O₉	C.megalocarpoides	[27]
66	Megalocarpoidolide H	C₂₄H₂₈O₁₀	C.megalocarpoides	[27]
67	Launine K	C₂₇H₃₆O₃	C. laui	[37]
68	Crassin A	C₁₇H₂₀O₄	C. crassifolius	[17]
69	Crassin B	C₁₇H₂₀O₄	C. crassifolius	[17]
70	Crassin C	C₂₁H₂₄O₆	C. crassifolius	[17]
71	Crassin D	C₂₀H₂₀O₅	C. crassifolius	[17]
72	Crassin E	C₁₉H₂₀O₃	C. crassifolius	[17]
73	Crassin F	C₁₉H₁₈O₇	C. crassifolius	[17]
74	Crassin G	C₂₀H₂₆O₅	C. crassifolius	[17]
75	Crassin H	C₂₁H₃₀O₅	C. crassifolius	[17]
76	Crassifolius A	C₂₀H₂₂O₅	C. crassifolius	[38]
77	Crassifolius B	C₂₁H₂₄O₆	C. crassifolius	[38]
78	Crassifolius C	C₂₁H₂₆O₅	C. crassifolius	[38]
79	Crolaevinoid C	C₂₇H₂₈O₆	C. laevigatus	[39]
80	Crolaevinoid D	C₂₇H₃₂O₈	C. laevigatus	[39]
81	Crolaevinoid E	C₂₀H₂₈O₆	C. laevigatus	[39]
82	Crolaevinoid F	C₂₁H₃₀O₅	C. laevigatus	[39]
83	Norcrassifolin	C₁₉H₁₈O₄	C. crassifolius	[28]
84	Hypolein A	C₂₀H₂₆O₄	C. hypoleucus	[24]
85	Hypolein B	C₂₀H₂₈O₃	C. hypoleucus	[24]
86	Hypolein C	C₂₀H₂₈O₃	C. hypoleucus	[24]
87	Cracroson E	C₁₉H₂₀O₆	C. crassifolius	[40]
88	Cracroson F	C₁₉H₂₀O₆	C. crassifolius	[40]
89	Cracroson G	C₂₁H₂₆O₇	C. crassifolius	[40]
90	12-Epi-megalocarpoidolide D	C₂₂H₂₂O₈	C. oligandrus	[18]
91	Crotonolins A	C₂₂H₂₂O₁₀	C. oligandrus	[18]
92	Crotonolins B	C₂₂H₂₂O₁₀	C. oligandrus	[18]

Table 2

Tigliane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
93	12-O-isobutyrylphorbol-13-decanoate	C₃₄H₅₂O₈	C. tiglium	[45]
94	12-O-(2-methyl)butyrylphorbol-13-octanoate	C₃₃H₅₀O₈	C. tiglium	[45]
95	12-O-[(2R)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate	C₂₉H₄₃NO₇	C. ciliatoglandulifer	[41]
96	12-O-[(2S)-N,N-dimethyl-3-methylbutanoyl]-4-deoxyphorbol 13-acetate	C₂₉H₄₃NO₇	C. ciliatoglandulifer	[41]
97	12-O-[(2R)-N,N-Dimethyl-3-methylbutanoyl]phorbol 13-acetate	C₂₉H₄₃NO₈	C. ciliatoglandulifer	[41]
98	12-O-[3-Methyl-2-butenoyl]-4-deoxyphorbol 13-acetate	C₂₇H₃₆NO₇	C. ciliatoglandulifer	[41]
99	12-O-(2-methyl)butyrylphorbol-13-tiglate	C₃₀H₄₂O₈	C. tiglium	[46]
100	12-O-tiglylphorbol-13-propionate	C₂₈H₃₈O₈	C. tiglium	[46]
101	13-O-acetylphorbol-20-oleate	C₄₀H₆₂O₈	C. tiglium	[46]
106	12-O-tiglyl-4-deoxy-4α-phorbol-13-(2-methyl)butyrate	C₃₀H₄₂O₇	C. tiglium	[46]
107	Alienusolin	C₄₂H₆₆O₈	C. alienus	[42]
108	12-O-acetyl-5,6-didehydro-7-oxophorbol-13-yl 2-methylbutanoate	C₂₇H₃₆O₉	C. tiglium	[47]
109	12-O-acetyl-5,6-didehydro-7-oxophorbol-13-yl2-methylpropanoate	C₂₆H₃₄O₉	C. tiglium	[47]
110	12-Oacetyl-5,6-didehydro-6,7-dihydro-7-hydroxyphorbol-13-yl 2-methylbutanoate	C₂₇H₃₈O₉	C. tiglium	[47]
111	12-O-decanoyl-7-hydroperoxy-phorbol-5-ene-13-acetate	C₃₂H₄₂O₁₀	C. mauritianus	[43]
112	20-deoxy-20-oxophorbol12-tiglate 13-(2-methyl)butyrate	C₃₀H₄₀O₈	C. tiglium	[48]
113	12-O-acetylphorbol-13-isobutyrate	C₂₆H₃₆O₈	C. tiglium	[48]
114	12-O-benzoylphorbol-13-(2-methyl)butyrate	C₃₂H₄₀O₈	C. tiglium	[48]
115	12-O-tiglyl-7-oxo-5-ene-phorbol-13-(2-methyl)butyrate	C₃₀H₄₀O₉	C. tiglium	[48]
116	13-O-(2-metyl)butyryl-4-deoxy-4a-phorbol	C₂₅H₃₆O₆	C. tiglium	[48]
117	Crotignoid A	C₃₀H₄₂O₁₀	C. tiglium	[49]
118	Crotignoid B	C₂₉H₄₀O₁₀	C. tiglium	[49]
119	Crotignoid C	C₃₀H₄₂O₉	C. tiglium	[49]
120	Crotignoid D	C₂₉H₄₀O₉	C. tiglium	[49]
121	Crotignoid E	C₂₉H₃₈O₉	C. tiglium	[49]
122	Crotignoid F	C₂₈H₃₆O₉	C. tiglium	[49]
123	Crotignoid G	C₃₀H₄₄O₈	C. tiglium	[49]
124	Crotignoid H	C₂₉H₃₈O₈	C. tiglium	[49]
125	Crotignoid I	C₃₀H₄₄O₈	C. tiglium	[49]
126	Crotignoid J	C₃₁H₃₈O₈	C. tiglium	[49]
127	Crotignoid K	C₂₉H₃₄O₇	C. tiglium	[49]
128	Crotusin A	C₃₆H₅₄O₁₀	C. caudatus	[44]
129	Crotusin B	C₄₆H₇₂O₁₁	C. caudatus	[44]
130	Crotusin C	C₃₆H₅₂O₁₁	C. caudatus	[44]
131	12-O-tiglylphorbol-4-deoxy- 4β-phorbol-13-acetate	C₂₇H₃₆O₇	C. tiglium	[50]
132	12-O-tiglylphorbol-4-deoxy-4β-phorbol-13-hexadecanoate	C₄₁H₆₄O₇	C. tiglium	[50]
133	13-O-acetylphorbol-4-deoxy-4β-phorbol-20-oleate	C₄₀H₆₂O₇	C. tiglium	[50]
134	13-O-acetylphorbol-4-deoxy-4β-phorbol-20-linoleate	C₄₀H₆₀O₇	C. tiglium	[50]
135	4-deoxy-20-oxophorbol 12-tiglyl 13-acetate	C₂₇H₃₄O₇	C. tiglium	[51]
136	7-oxo-5-ene-phorbol-13-(2-methylbutyrate)	C₂₅H₃₄O₈	C. tiglium	[51]
137	7-hydroxyl-phorbol-5-ene-13-(2-methyl)butyrate	C₂₅H₃₆O₈	C. tiglium	[51]

Table 3

Kaurane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
149	Caracasine	C₂₁H₃₀O₃	C. caracasana	[53]
150	Caracasine acid	C₂₀H₂₈O₃	C. caracasana	[53]
151	Kongensin A	C₂₂H₃₀O₅	C. kongensis	[56]
152	Kongensin B	C₂₂H₃₀O₆	C. kongensis	[56]
153	Kongensin C	C₂₀H₂₈O₅	C. kongensis	[56]
154	Kongensin D	C₂₀H₂₈O₄	C. kongensis	[57]
155	Kongensin E	C₂₆H₃₆O₇	C. kongensis	[57]
156	Kongensin F	C₂₄H₃₄O₅	C. kongensis	[58]
157	Crotonkinin A	C₂₀H₃₀O₂	C. tonkinensis	[62]
158	Crotonkinin B	C₂₂H₃₂O₄	C. tonkinensis	[62]
159	14-epi-hyalic acid	C₂₀H₂₈O₄	C. argyrophylloides	[63]
160	14-[(2-methylbutanoyl)oxy]-3,4-seco-ent-kaura-4(19),16-dien-3-oic acid	C₂₅H₃₉O₄	C. megistocarpus	[54]
161	14-{[(2Z)-2-methylbut-2-enoyl]oxy}-3,4-seco-ent-kaura-4(19),16-dien-3-oic acid	C₂₅H₃₇O₄	C. megistocarpus	[54]
162	ent-11β-acetoxykaur-16-en-18-ol	C₂₂H₃₄O₃	C. tonkinensis	[64]
163	ent-11α-hydroxy-18-acetoxykaur-16-ene	C₂₂H₃₄O₃	C. tonkinensis	[64]
164	ent-14β-hydroxy-18-acetoxykaur-16-ene	C₂₂H₃₄O₃	C. tonkinensis	[64]
165	ent-7α-hydroxy-18-acetoxykaur-16-ene	C₂₂H₃₄O₃	C. tonkinensis	[64]
166	ent-14S*-hydroxykaur-16-en-19-oic acid	C₂₀H₃₀O₃	C. pseudopulchellus	[65]
167	ent-14S*,17-dihydroxykaur-15-en-19-oic acid	C₂₀H₃₀O₄	C. pseudopulchellus	[65]
168	ent-3,4-seco-17-oxo-kaur-4(19),15(16)-dien-3-oic acid	C₂₀H₂₈O₃	C. oblongifolius	[55]
169	Crotonkinin C	C₂₂H₃₀O₅	C. tonkinensis	[66]
170	Crotonkinin D	C₂₄H₃₄O₆	C. tonkinensis	[66]
171	Crotonkinin E	C₂₄H₃₄O₅	C. tonkinensis	[66]
172	Crotonkinin F	C₂₄H₃₄O₅	C. tonkinensis	[66]
173	Crotonkinin G	C₂₃H₃₆O₅	C. tonkinensis	[66]
174	Crotonkinin H	C₂₂H₃₆O₄	C. tonkinensis	[66]
175	Crotonkinin I	C₂₄H₃₆O₅	C. tonkinensis	[66]
176	Crotonkinin J	C₂₃H₃₄O₅	C. tonkinensis	[66]
177	14β-hydroxy-3-oxo-ent-kaur-16-ene	C₂₀H₃₀O₂	C. kongensis	[67]
178	Kongeniod A	C₂₁H₃₀O₃	C. kongensis	[59]
179	Kongeniod B	C₂₁H₃₀O₄	C. kongensis	[59]
180	Kongeniod C	C₂₃H₃₂O₅	C. kongensis	[59]
181	15-oxo-17(10′-α-pinenyl)-kauran-18-oic acid	C₃₀H₄₄O₃	C. limae	[35]
182	Micansinoic acid	C₄₀H₅₈O₇	C. micans	[60]
183	Isomicansinoic acid	C₄₀H₅₈O₇	C. micans	[60]
184	Dimethylester of micansinoic	C₄₂H₆₂O₇	C. micans	[60]
185	Methyl-micansinoic acid	C₄₁H₆₀O₇	C. micans	[60]
186	Ethyl-micansinoic acid	C₄₂H₆₂O₇	C. micans	[60]
187	Crotonkinensin C	C₄₀H₆₂O₈	C. tonkinensis	[61]
188	Crotonkinensin D	C₄₄H₆₆O₁₀	C. tonkinensis	[61]

Table 4

Crotofolane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
189	Crotocascarin A	C₂₅H₃₂O₇	C. cascarilloides	[68]
190	Crotocascarin B	C₂₅H₃₂O₇	C. cascarilloides	[68]
191	Crotocascarin C	C₂₅H₃₂O₈	C. cascarilloides	[68]
192	Crotocascarin D	C₂₅H₃₂O₆	C. cascarilloides	[68]
193	Crotocascarin E	C₂₆H₃₄O₈	C. cascarilloides	[68]
194	Crotocascarin F	C₂₄H₃₀O₇	C. cascarilloides	[68]
195	Crotocascarin G	C₂₄H₃₀O₇	C. cascarilloides	[68]
196	Crotocascarin H	C₂₄H₃₀O₈	C. cascarilloides	[68]
197	Crotocascarin α	C₂₄H₃₂O₈	C. cascarilloides	[68]
198	Crotocascarin β	C₂₄H₃₂O₇	C. cascarilloides	[68]
199	(5β,6β)-5,6: 13,16-diepoxycrotofola-4(9),10(18),13,15-tetraen-1-one	C₂₀H₂₂O₃	C. argyrophyllus	[72]
200	(5β,6β)-5,6: 13,16-diepoxy-2-epicrotofola-4(9),10(18),13,15-tetraen-1-one	C₂₀H₂₂O₃	C. argyrophyllus	[72]
201	(5β,6β)-5,6: 13,16-diepoxy-16-hydroxycrotofola-4(9),10(18),13,15-tetraen-1-one	C₂₀H₂₂O₄	C. argyrophyllus	[72]
202	(5β,6β)-5,6: 13,16-diepoxy-16-hydroxy-2-epi-crotofola-4(9),10(18),13,15-tetraen-1-one	C₂₀H₂₂O₄	C. argyrophyllus	[72]
203	Crotocarasin A	C₂₀H₂₂O₄	C. caracasanus	[73]
204	Crotocarasin B	C₂₀H₂₂O₄	C. caracasanus	[73]
205	Crotocarasin C	C₂₂H₂₆O₅	C. caracasanus	[73]
206	Crotocarasin D	C₂₂H₂₆O₅	C. caracasanus	[73]
207	EBC-162	C₂₀H₂₄O₂	C. insularis	[74]
208	EBC-233	C₂₀H₂₄O₄	C. insularis	[74]
209	EBC-300	C₂₀H₂₄O₄	C. insularis	[74]
210	EBC-240	C₂₀H₂₆O₅	C. insularis	[74]
211	EBC-241	C₂₀H₂₆O₅	C. insularis	[74]
212	Crotocascarin I	C₂₀H₂₄O₅	C. cascarilloides	[69]
213	Crotocascarin J	C₂₀H₂₄O₆	C. cascarilloides	[69]
214	Crotocascarin K	C₂₀H₂₄O₅	C. cascarilloides	[69]
215	Crotocascarin γ	C₁₉H₂₄O₆	C. cascarilloides	[69]
216	Crotocascarin L	C₂₂H₂₆O₇	C. cascarilloides	[70]
217	Crotocascarin M	C₂₁H₂₆O₆	C. cascarilloides	[70]
218	Crotocascarin N	C₂₀H₂₂O₆	C. cascarilloides	[70]
219	Crotocascarin O	C₂₅H₃₄O₉	C. cascarilloides	[70]
220	Crotocascarin P	C₂₅H₃₄O₈	C. cascarilloides	[70]
221	Crotocascarin Q	C₂₅H₃₂O₇	C. cascarilloides	[70]
222	Neocrotocascarin	C₂₅H₃₂O₈	C. cascarilloides	[70]
223	Crotodichogamoin A	C₂₀H₂₂O₄	C. dichogamus	[75]
224	Crotodichogamoin B	C₂₀H₂₂O₂	C. dichogamus	[75]
225	Cascarinoid A	C₂₈H₃₁NO₅	C. cascarilloides	[71]
226	Cascarinoid B	C₂₈H₃₁NO₅	C. cascarilloides	[71]
227	Cascarinoid C	C₂₈H₃₁NO₆	C. cascarilloides	[71]

Table 5

Labdane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
228	Labdinine N	C₂₀H₃₄O₃	C. laui	[76]
229	ent-12,15-dioxo-3,4-seco-4,8,13-labdatrien-3-oic acid	C₂₀H₂₈O₄	C. stipuliformis	[78]
230	ent-12,15-epoxy-3,4-seco-4,8,12,14-labdatetraen-3-oic acid	C₂₀H₂₈O₃	C. stipuliformis	[78]
231	ent-15-nor-14-oxo-3,4-seco-4,8,12(E)-labdatrien-3-oic acid	C₁₉H₂₈O₃	C. stipuliformis	[78]
232	ent-12,15-dioxo-8,13-labdadien-3a-ol	C₂₀H₂₈O₃	C. stipuliformis	[78]
233	Crotonlaevin A	C₁₈H₃₀O₄	C. laevigatus	[79]
234	Crotonlaevin B	C₂₀H₃₂O₅	C. laevigatus	[79]
235	Crotonlaevin C	C₂₁H₃₄O₅	C. laevigatus	[79]
236	Crotonlaevin D	C₁₈H₃₀O₃	C. laevigatus	[79]
237	Crotonlaevin E	C₂₀H₃₂O₅	C. laevigatus	[79]
238	Crotonlaevin F	C₂₂H₃₄O₆	C. laevigatus	[79]
239	Crotonlaevin G	C₂₂H₃₆O₅	C. laevigatus	[79]
240	Crotonlaevin H	C₂₂H₃₆O₅	C. laevigatus	[79]
241	Crotonlaevin I	C₂₀H₃₄O₄	C. laevigatus	[79]
242	Crotonlaevin J	C₂₀H₃₀O₃	C. laevigatus	[79]
243	Crotonlaevin K	C₂₀H₂₈O₃	C. laevigatus	[79]
244	Crotonlaevin L	C₂₀H₃₀O₄	C. laevigatus	[79]
245	Crotonlaevin M	C₂₀H₃₀O₄	C. laevigatus	[79]
246	Crotonlaevin N	C₂₀H₃₀O₃	C. laevigatus	[79]
247	Crotonlaevin O	C₂₀H₃₀O₃	C. laevigatus	[79]
248	Crotonlaevin P	C₂₀H₃₀O₃	C. laevigatus	[79]
249	Crotonolide I	C₂₀H₃₄O₃	C. laui	[21]
250	Crotonolide J	C₁₉H₃₀O₃	C. laui	[21]
251	Launine A	C₁₉H₃₂O₃	C. laui	[82]
252	Launine B	C₁₉H₃₂O₄	C. laui	[82]
253	Launine C	C₂₀H₃₄O₃	C. laui	[82]
254	Launine D	C₂₀H₃₄O₃	C. laui	[82]
255	Launine E	C₂₀H₃₂O₅	C. laui	[82]
256	Launine F	C₂₀H₃₂O₅	C. laui	[82]
257	Launine G	C₂₀H₃₀O₄	C. laui	[82]
258	Launine H	C₂₀H₃₀O₄	C. laui	[82]
259	Launine I	C₂₀H₃₄O₃	C. laui	[82]
260	15,16-epoxy-4-hydroxy-labda-13(16),14-dien-3,12-dione	C₂₀H₂₈O₄	C. jacobinensis	[77]
261	Crotondecalvatin A	C₂₉H₄₂O₄	C. decalvatus	[80]
262	Crotondecalvatin B	C₃₀H₄₂O₆	C. decalvatus	[80]
263	Bicrotonol A	C₄₀H₆₈O₄	C. crassifolius	[81]

Table 6

Cembrane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
264	Launine O	C₂₀H₃₄O₂	C. laui	[76]
265	Launine P	C₂₁H₃₆O₂	C. laui	[76]
266	Furanocembranoid 1	C₂₀H₃₀O₂	C. oblongifolius	[83]
267	Furanocembranoid 2	C₂₀H₃₀O₃	C. oblongifolius	[83]
268	Furanocembranoid 3	C₂₀H₃₂O₄	C. oblongifolius	[83]
269	Furanocembranoid 4	C₂₀H₃₂O₅	C. oblongifolius	[83]
270	Laevigatlactone A	C₂₀H₃₀O₃	C. laeVigatus	[84]
271	Laevigatlactone C	C₂₀H₃₀O₃	C. laeVigatus	[84]
272	Laevigatlactone B	C₂₀H₃₀O₃	C. laeVigatus	[84]
273	Laevigatlactone D	C₂₀H₃₀O₃	C. laeVigatus	[84]
274	Laevigatlactone E	C₂₀H₃₀O₄	C. laeVigatus	[84]
275	Laevigatlactone F	C₂₀H₃₀O₅	C. laeVigatus	[84]
276	(+)-[1R,2S,7S,8S,12R*]-7,8-Epoxy-2,12-cyclocembra-3E,10Zdien-20,10-olide	C₂₀H₂₈O₃	C. gratissimus	[85]
277	(+)-[1R,10R]-Cembra-2E,4E,7E,11Z-tetraen-20,10-olide	C₂₀H₂₈O₂	C. gratissimus	[85]
278	(+)-[1R,4S,10R*]-4-Hydroxycembra-2E,7E,11Z-trien-20,10-olide	C₂₀H₃₀O₃	C. gratissimus	[85]
279	(−)-[1R,4R,10R*]-4-Hydroxycembra-2E,7E,11Z-trien-20,10-olide	C₂₀H₃₀O₃	C. gratissimus	[85]
280	(−)-(1R,4R,10R*)-4-Methoxycembra-2E,7E,11Z-trien-20,10-olide	C₂₁H₃₂O₃	C. gratissimus	[86]
281	(−)-(1S,4R,10R*)-1-Hydroxy-4-methoxycembra-2E,7E,11Ztrien-20,10-olide	C₂₁H₃₂O₄	C. gratissimus	[86]
282	(−)-(1S,4S,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olide	C₂₀H₃₀O₄	C. gratissimus	[86]
283	(−)-(1S,4S,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olide	C₂₀H₃₀O₄	C. gratissimus	[86]
284	(+)-(10R*)-Cembra-1E,3E,7E,11Z,16-pentaen-20,10-olide	C₂₀H₂₆O	C. gratissimus	[86]
285	(+)-(10R*)-Cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olide	C₂₀H₂₆O	C. gratissimus	[86]
286	(+)-(5R,10R)-5-Methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olide	C₂₁H₃₀O₃	C. gratissimus	[86]
287	(+)-(1S,4S,7R,10R)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olide	C₂₀H₃₀O₅	C. gratissimus	[86]
288	(−)-(1S,4S,7S,10R)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olide	C₂₀H₃₀O₃	C. gratissimus	[86]
289	(+)-(1S,4R,8S,10R)-1,4,8-Trihydroxycembra-2E,6E,11Z-trien-20,10-olide	C₂₀H₃₀O₅	C. gratissimus	[86]
290	Cembranoid 1	C₂₀H₃₀O₄	C. longissimus	[87]
291	Cembranoid 2	C₂₀H₃₀O₃	C. longissimus	[87]
281	(−)-(1S,4R,10R*)-1-Hydroxy-4-methoxycembra-2E,7E,11Ztrien-20,10-olide	C₂₁H₃₂O₄	C. gratissimus	[86]
282	(−)-(1S,4S,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olide	C₂₀H₃₀O₄	C. gratissimus	[86]
283	(−)-(1S,4S,10R*)-1,4-Dihydroxycembra-2E,7E,11Z-trien-20,10-olide	C₂₀H₃₀O₄	C. gratissimus	[86]
284	(+)-(10R*)-Cembra-1E,3E,7E,11Z,16-pentaen-20,10-olide	C₂₀H₂₆O	C. gratissimus	[86]
285	(+)-(10R*)-Cembra-1Z,3Z,7E,11Z,15-pentaen-20,10-olide	C₂₀H₂₆O	C. gratissimus	[86]
286	(+)-(5R,10R)-5-Methoxycembra-1E,3E,7E,11Z,15-pentaen-20,10-olide	C₂₁H₃₀O₃	C. gratissimus	[86]
287	(+)-(1S,4S,7R,10R)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olide	C₂₀H₃₀O₅	C. gratissimus	[86]
288	(−)-(1S,4S,7S,10R)-1,4,7-Trihydroxycembra-2E,8(19),11Z-trien-20,10-olide	C₂₀H₃₀O₃	C. gratissimus	[86]
289	(+)-(1S,4R,8S,10R)-1,4,8-Trihydroxycembra-2E,6E,11Z-trien-20,10-olide	C₂₀H₃₀O₅	C. gratissimus	[86]
290	Cembranoid 1	C₂₀H₃₀O₄	C. longissimus	[87]
291	Cembranoid 2	C₂₀H₃₀O₃	C. longissimus	[87]

Table 7

Abietane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
292	Isolophanthin E	C₂₀H₃₀O₃	C. megalocarpoides	[27]
293	rel-(1R,4aR,5R,8R)-methyl-7-(1-(methoxycarbonyl)vinyl)-5,8-diacetoxy-1,2,3,4a,5,6,7,8,9,10,10a-dodecahydro-1,4a-dimethyl-2-oxophenanthrene-1-carboxylate	C₂₆H₃₄O₉	C. argyrophylloides	[63]
294	Crotontomentosin A	C₂₀H₂₆O₂	C. caudatus	[88]
295	Crotontomentosin B	C₂₀H₃₀O₃	C. caudatus	[88]
296	Crotontomentosin D	C₂₀H₂₄O₂	C. caudatus	[88]
297	Crotontomentosin C	C₂₀H₂₈O₂	C. caudatus	[88]
298	Crotontomentosin E	C₂₂H₃₂O₃	C. caudatus	[88]
299	Crotolaevigatone A	C₂₀H₂₄O₃	C. laevigatus	[89]
300	Crotolaevigatone B	C₂₀H₂₆O₂	C. laevigatus	[89]
301	Crotolaevigatone C	C₂₀H₂₆O₃	C. laevigatus	[89]
302	Crotolaevigatone D	C₂₀H₂₈O₄	C. laevigatus	[89]
303	Crotolaevigatone E	C₁₉H₂₄O₂	C. laevigatus	[89]
304	Crotolaevigatone F	C₂₀H₃₀O₄	C. laevigatus	[89]
305	Crotolaevigatone G	C₂₀H₃₀O₄	C. laevigatus	[89]

Table 8

Casbane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
306	1,4-dihydroxy-2E,6E,12E-trien-5-one-casbane	C₂₀H₃₀O₃	C. nepetaefolius	[90]
307	4-hydroxy-2E,6E,12E-5-one-casbane	C₂₀H₂₉O₃	C. nepetaefolius	[90]
308	1-hydroxy-(2E,6Z,12E)-casba-2,6,12-triene-4,5-dione	C₂₀H₂₈O₃	C. argyrophyllus	[91]
309	6E,12E-casba-1,3,6,12-tetraen-1,4-epoxy-5-one	C₂₀H₂₆O₂	C. argyrophyllus	[91]
310	(2E,5β,6E,12E)-5-hydroxycasba-2,6,12-trien-4-one	C₂₀H₃₀O₂	C. argyrophyllus	[72]
311	EBC-324	C₂₀H₂₈O₅	C. insularis	[92]
312	EBC-329	C₂₀H₂₆O₄	C. insularis	[92]

Table 9

Halimane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
313	Crassifoliusin A	C₂₁H₂₄O₅	C. crassifolius	[95]
314	Crotontomentosin F	C₂₁H₃₀O₃	C. caudatus	[88]
315	Crolaevinoid A	C₂₇H₃₀O₇	C. laevigatus	[39]
316	Crolaevinoid B	C₂₀H₂₆O₄	C. laevigatus	[39]
317	Crothalimene A	C₂₀H₂₆O₄	C. dichogamus	[75]
318	Crothalimene B	C₂₀H₃₀O₂	C. dichogamus	[75]

Table 10

Pimarane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
319	ent-3β-hydroxypimara-8(14),9,15-trien-12-one	C₂₀H₂₈O₂	C. insularis	[98]
320	EBC-316	C₂₀H₂₆O₂	C. insularis	[99]
321	EBC-325	C₂₀H₂₆O₄	C. insularis	[99]
322	EBC-326	C₂₀H₂₆O₄	C. insularis	[99]
323	EBC-327	C₂₀H₂₄O₃	C. insularis	[99]
324	EBC-345	C₂₀H₃₀O₄	C. insularis	[99]

Table 11

Cleistanthane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
325	3-hydroxycleistantha-13(17),15-diene	C₂₀H₃₂O	C. oblongifolius	[93]
326	3,4-seco-cleistantha-4(18),13(17),15-trien-3-oic acid	C₂₀H₃₀O₂	C. oblongifolius	[93]
327	rel-(5β,8α,10α)-8-hydroxy-13-methylpodocarpa-9(11),13-diene-3,12-dione	C₁₈H₂₅O₃	C. regelianus	[94]

Table 12

Grayanane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
328	Crotonkinensin A	C₂₀H₂₄O₄	C. tonkinensis	[100]
329	Crotonkinensin B	C₂₀H₂₆O₃	C. tonkinensis	[100]

Table 13

Atisane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
330	Crotobarin	C₂₂H₂₈O₅	C. barorum	[101]
331	Crotogoudin	C₂₀H₂₆O₃	C. goudotii	[101]

Table 14

Phytane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
332	Launine L	C₂₀H₃₂O₃	C. laui	[37]
333	Launine M	C₂₀H₃₂O₂	C. laui	[37]

Table 15

Laevinane type diterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
334	Crolaevinoid G	C₂₀H₂₄O₆	C. laevigatus	[39]
335	Crolaevinoid H	C₂₁H₂₆O₆	C. laevigatus	[39]

Table 16

Meroditerpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
336	Steenkrotin A	C₂₀H₂₄O₆	C. steenkampianus	[102]
337	Steenkrotin B	C₂₀H₂₈O₇	C. steenkampianus	[102]
338	Norcrassin A	C₁₇H₂₂O₇	C. crassifolius	[81]
339	Cracroson D	C₂₁H₂₆O₆	C. crassifolius	[40]

Table 17

Sesquiterpenoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
340	6α -methoxy-cyperene	C₁₆H₂₆O	C. muscicarpa	[103]
341	rel-(1R,4S,6R,7S,8αR)-decahydro-1-(hydroxymethyl)-4,9,9-trimethyl-4,7-(epoxymethano)azulen-6-ol	C₁₅H₂₆O₃	C. regelianus	[94]
342	Blumenol A	C₁₃H₂₀O₃	C. pedicellatus	[104]
343	Crocrassins A	C₁₅H₂₄O₃	C. crassifolius	[105]
344	Crocrassins B	C₁₆H₂₆O₃	C. crassifolius	[105]
345	1,3,5-cadinatriene-(7R,10S)-diol	C₁₅H₂₅O₂	C. dichogamus	[75]
346	Cracroson H	C₁₅H₂₂O₃	C. crassifolius	[40]

Table 18

Sesterterpenoid from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
347	Pseudopulchellol	C₂₅H₄₀O	C.pseudopulchellus	[106]

Table 19

Triterpenoid from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
348	3α-hydroxy-urs-12,15-dien	C₃₀H₄₈O	C. bonplandianum	[107]

Table 20

Glycosides from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
349	Cyperenoic acid-9-O-β-d-glucopyranoside	C₂₁H₃₂O₈	C. crassifolius	[108]
350	3-O-β-d-xylopyranosylspathodic acid	C₃₅H₅₆O₉	C. lachnocarpus	[109]
351	Helichrysoside-3′-methylether	C₃₁H₂₈O₁₄	C. zambesicus	[110]
352	Crotonionoside A	C₂₉H₄₂O₁₁	C. cascarilloides	[111]
353	Crotonionoside B	C₃₀H₄₄O₁₂	C. cascarilloides	[111]
354	Crotonionoside C	C₂₄H₄₂O₁₂	C. cascarilloides	[111]
355	Crotonionoside D	C₃₁H₄₆O₁₄	C. cascarilloides	[111]
356	Crotonionoside E	C₃₅H₅₂O₁₆	C. cascarilloides	[111]
357	Crotonionoside F	C₂₄H₄₂O₁₁	C. cascarilloides	[111]
358	Crotonionoside G	C₂₉H₄₀O₁₁	C. cascarilloides	[111]
359	Oblongionoside A	C₂₄H₄₂O₁₂	C. oblongifolius	[112]
360	Oblongionoside B	C₂₄H₄₂O₁₂	C. oblongifolius	[112]
361	Oblongionoside C	C₂₄H₄₄O₁₁	C. oblongifolius	[112]
362	Oblongionoside D	C₂₄H₄₄O₁₁	C. oblongifolius	[112]
363	Oblongionoside E	C₁₉H₃₆O₈	C. oblongifolius	[112]
364	Oblongionoside F	C₁₉H₃₆O₈	C. oblongifolius	[112]
365	Blumenol A glucoside	C₁₉H₃₀O₈	C. pedicellatus	[10]
366	Sparsioside	C₅₃H₁₀₂O₁₀	C. sparsiorus	[113]
367	3,12-dioxo-15,16-epoxy-4α-hydroxy-6-(β-glucopyranosyl)-ent-neo-clerodan-13(16),14-diene	C₂₆H₃₈O₁₀	C. limae	[35]
368	Isocrotofolane glucoside	C₂₆H₃₈O₉	C. cascarilloides	[69]
369	2-methoxyphenol-β-d-(6-O-β-d-apiofuranosyl) glucopyranoside	C₁₈H₂₆O₁₁	C. cascarilloides	[69]

Table 21

Alkaloids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
370	Crotamide A	C₃₆H₆₅NO	C. sparsiflorus	[114]
371	Crotamide B	C₃₈H₆₉NO	C. sparsiflorus	[114]
372	Crotonine	C₁₂H₁₄N₂O₄	C. tiglium	[97]
373	Crotonimide A	C₁₆H₂₀N₂O₃	C. pullei	[115]
374	Crotsparsidine	C₁₇H₁₇O₃N	C. sparsiflorus	[96]
375	Crotonimide C.	C₂₀H₂₀N₂O₃	C. alienus	[42]
376	6-Hydroxy-1-methyl-2-dimethyl-3,4-tetrahydro-b-carbo-line	C₁₄H₁₉N₂O	C. heliotropiifolius	[116]
377	N-trans-feruloyl-3,5-dihydroxyindolin-2-one	C₂₀H₂₀N₂O₆	C. echioides	[117]

Table 22

Benzoate derivatives from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
378	2′-(3′’,4′’-dihydroxyphenyl)-ethyl-4-hydroxybenzoate	C₁₅H₁₄O₅	C. sylvaticus	[118]
379	3-(4-hydroxy-3,5-dimethoxyphenyl)-propyl benzoate	C₁₈H₂₀O₅	C. hutchinsonianus	[119]
380	3-(4-hydroxyphenyl)-propyl benzoate	C₁₆H₁₆O₃	C. hutchinsonianus	[119]

Table 23

Pyran-2-one derivatives from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
381	Crotonpyrone A	C₁₇H₂₈O₃	C. crassifolius	[120]
382	Crotonpyrone B	C₁₇H₂₆O₃	C. crassifolius	[120]
383	Crotonpyrone C	C₁₉H₂₈O₃	C. crassifolius	[121]

Table 24

Cyclicpeptides from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
384	Crotogossamide	C₃₇H₅₆N₁₀O₁₁	C. gossypifolius	[122]
385	[1−9-NαC]-crourorb A1	C₃₇H₅₆N₁₀O₁₁	C. urucurana	[123]

Table 25

Tropone derivatives from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
386	Crototropone	C₁₀H₁₂O₄	C. zehntneri	[124]
387	Pernambucone	C₁₅H₁₈O₂	C. argyroglossum	[125]

Table 26

Limonoids from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
388	Musidunin	C₃₁H₃₈O₁₁	C. jatrophoides	[126]
389	Musiduol	C₃₀H₃₈O₁₀	C. jatrophoides	[126]

Table 27

Miscellaneous compounds from the genus Croton.

No.	Compound Name	Molecular Formula	Sources	Ref
390	Crotoncaudatin	C₂₂H₂₂O₉	C. caudatus	[127]
391	8S-(−)-8-(4-hydroxy-3-methoxybenzoyl)-dihydrofuran-8(8′H)-one	C₂₀H₃₀O₂	C. kongensis	[67]
392	Lobaceride	C₃₅H₅₈O₆	C. lobatus	[129]
393	Laevifolin A	C₂₉H₃₈O₄	C. laevifolius	[128]
394	Laevifolin B	C₂₉H₃₈O₄	C. laevifolius	[128]
395	2,6-Dimethyl-1-oxo-4-indanecarboxylic acid	C₁₂H₁₂O₃	C. steenkampianus	[102]
396	3(3′-Methoxy-5′-phenylfuran-2′-yl)propan-1-ol	C₁₄H₁₆O₃	C. oblongifolius	[22]
397	Sparsifol	C₇H₁₅O₆	C. sparsiflorus	[96]
398	Sparsioamide	C₄₃H₈₁NO₅	C. sparsiflorus	[113]
399	hexyl Z-ferulate	C₁₆H₂₂O₄	C. laevigatus	[89]

2.1. Diterpenoids

Phytochemical investigations on Croton species revealed the predominant secondary metabolites as diterpenoids, including clerodane, tigliane, kaurane, crotofolane, labdane, cembrane, abietane, casbane, halimane, pimarane, cleistanthane, grayanane, atisane, phytane, and laevinane diterpenoids. Three hundred & thirty-nine new diterpenoids (1–339) were reported from Croton species.

2.1.1. Clerodanes

Ninety-two new clerodane diterpenoids (1–92) were isolated from Croton species, including two clerodane diterpenoid with acyclic at C-9s, eight clerodane diterpenoids with butenolide at C-9, and 82 furan-clerodane diterpenoids [11]. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 1 and Table 1. Two new clerodane diterpenoids with acyclic side chain at C-9, ent-3,13E-clerodadiene-15-formate (1) and 3α,4α,15,16-tetrahydroxy-ent-neo-cleroda-13E-ene (45), were isolated from the roots of C. sylvaticus [12] and the roots of C. limae [13], respectively. Eight new clerodane diterpenoids with butenolide at C-9 (2, 3, 5, 13, 14, 75, 91, 92) were obtained from three Croton species (C. crassifolius, C. glabellus, and C. oligandrus) [14,15,16,17,18]. Furan-clerodane diterpenoids are abundant in Croton species, and 82 new ones were isolated from different Croton species. For example, Centrafricine I (4) from C. mayumbensis was a new furan-clerodane diterpenoid with a 6, 18-γ-lactone ring [19]. Two novel rearranged ent-clerodane diterpenoids Laevinoids A, B (21, 22) containing an unusual 3/5 bicyclic ring were obtained from the branches and leaves of C. laevigatus; 22 represents the first chlorinated example of the clerodane family [20]. Compounds (23–27) bearing a C-19/C-20 six-membered ring were identified from C. laui [21]. Phytochemical investigations on three Croton species (C. oblongifolius, C. yanhuii, and C. hypoleucus) afforded six new furan-clerodanoids (12, 36, 37, 84–86) with a 3,4-epoxy moiety [22,23,24]. Crotoeurins A–C (40–42) were found from the twigs and leaves of C. euryphyllus. Among them, crotoeurin A (40) was a nor-clerodane diterpenoid dimer with a unique cyclobutane ring via a [2 + 2] cycloaddition [25]. Three new furan-clerodane diterpenoids, cracroson A–C (46–48) were obtained from C. crassifolius, while cracroson C (48) represents the first example of a clerodane diterpenoid alkaloid [26]. Twelve new ent-clerodanoids (55, 66) were isolated from the roots of C. megalocarpoides. Among them, compounds (58–66) possessed 9, 12-γ-lactone ring [27]. Investigation on the roots of C. crassifolius afforded eight new clerodanoids, crassins A−H (68–75). Among them, crassins A–B (68, 69) represents ring B rearranged clerodanoids, whereas crassins C (70) was ring A rearranged one [17]. One new nor-clerodane diterpenoid, norcrassifolin (83), with a 1,12-lactone six-membered ring, was isolated from C. crassifolius [28].

2.1.2. Tiglianes

Fifty-six new tigliane diterpenoids (93–148) were reported from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 2 and Table 2. Investigations on the aerial parts of C. ciliatoglandulifer produced four new tiglianoids (95–98). Among them, tiglianoids (95–97) possess a N,N-dimethyl moiety at 2′position [41]. Alienusolin (107) and compound (111) were obtained from the roots and the leaves of C. alienus and the leaves of C. mauritianus, respectively [42,43]. The twigs and leaves of C. caudatus produced three new tiglianoids, crotusins A–C (128–130) [44]. Tigliane diterpenoids were abundant in C. tiglium, other 47 new ones (93, 94, 99–106, 108–110, 112–127, 131–148) were isolated from C. tiglium [45,46,47,48,49,50,51,52]. Among them, compound (112) was the first tiglianoid with the C20-aldehyde group [48].

2.1.3. Kauranes

Fourty new kaurane diterpenoids (149–188) were found from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 3 and Table 3. Five new 3,4-seco ent-kauranes (149–150, 160–161, 168) were isolated from C. caracasana [53], C. megistocarpus [54], and C. oblongifolius [55], respectively. Investigations on C. kongensis afforded eight new 8,9-seco-ent-kaurane diterpenes (151–154, 156, 178–180) [56,57,58,59]. Compound 181, one new kaurane bearing a monoterpene unit at C-16, was found from C. limae [35]. From the stems of C. micans, five new 3,4-seco-ent-kaurene dimers (182–186) were isolated [60], while other two dimeric ent-kaurane diterpenoids (187–188) were elucidated from C. tonkinensis [61].

2.1.4. Crotofolanes

Thirty-nine new crotofolane diterpenoids (189–227) were obtained from Croton species. Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 4 and Table 4. Twenty-four new crotofolane diterpenoids (189–198, 212–222, 225–227) were isolated from C. caracasanus [68,69,70,71]. Among them, three new crotofolane diterpenoid alkaloids, cascarinoids A–C (225–227), were firstly found. Investigations on C. argyrophyllus gave four new crotofolanes (199–202) [72]. Crotocarasin A–D (203–206) were isolated from the stems of C. caracasanus [73]. Five new 1, 14-seco-crotofolanes from C. insularis were obtained [74], while C. dichogamus yielded crotodichogamoin A–B (223–224) [75].

2.1.5. Labdanes

Thirty-six new labdane diterpenoids (228–263) were isolated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 5 and Table 5 12 new labdanes (228, 249–259) were isolated from C. laui [21,76,77]. From the leaves of C. stipuliformis, three 3,4-seco-ent-labdanes (229–231) and one ent-labdane (232) were obtained [78]. Investigation of C. laevigatus led to the isolation of 16 new labdanes (233–248). Among them, crotonlaevins A–B (233, 234), represents rare labdanes with a dodecahydronaphtho [1,2-c] furan moiety [79]. Three new labdane diterpenoids (260–262) were found from C. jacobinensis [77] and C. decalvatus [80], respectively. Bicrotonol A (263), one dimeric labdane-type diterpenoid, was obtained from the roots of C. crassifolius [81].

2.1.6. Cembranes

A total of 28 new cembrane diterpenoids (264–291) were obtained from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 6 and Table 6. launine O-P (264, 265), two new cembranes, were reported from the aerial parts of C. laui [76]. Investigations on the stem bark of C. oblongifolius afforded four new furanocembranoids (266–269) [83]. laevigatlactones A–F (270–275), six new cembranoids possessing a rare six-membered lactone moiety attached to C-1 and C-20, were firstly isolated from C. laevigatus [84]. 14 new cembranoids (276–289) were found from C. gratissimus [85,86]. Among them, compound 276 was first example of a 2,12-cyclocembranolide. The leaves of C. longissimus produced two new cembranes (290, 291) [87].

2.1.7. Abietanes

Fourteen new abietane diterpenoids (292–305) were isolated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 7 and Table 7. Two new abietanes (292, 293) were obtained from C. megalocarpoides [27], and C. argyrophylloides [63], respectively. Investigation of C. caudatus led to the isolation of 5 new abietanes (294–298). Among them, crotontomentosin A (294) was a 9,10-seco abietane [88]. Crotolaevigatones A–G (299–305), 7 new abietanes were found from the twigs and leaves of C. laevigatus, and compounds (304, 305) possessed a 9,13-epidioxy moiety [89].

2.1.8. Casbanes

Seven new casbane diterpenoids (306–312) were found from Croton species. Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 8 and Table 8. Five new casbane s (306–310) were reported from C. nepetaefolius [90], and C. argyrophyllus [72,91], respectively. Investigations on the stem bark of C. insularis afforded two new casbanes, EBC-324 (311) and EBC-329 (312). Among them, EBC-329 (312) represented the first natural seco-casbane diterpene, while EBC-324 (311) was the first endoperoxide casbane [92].

2.1.9. Halimanes

Six new halimane diterpenoids (313–318) were reported from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 8 and Table 9. Investigations on the stem bark of C. oblongifolius afforded two new cleistanthanes (325, 326). Among them, compound 326 was a 3,4-seco cleistanthane [93]. One new bis-nor-cleistanthane diterpenoid (327), was found from the twigs and leaves of C. caudatus [94].

2.1.10. Pimaranes

Six new pimarane diterpenoids (319–324) were obtained from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 8 and Table 10. All six new pimaranes (319–324) were isolated from C. insularis [96,97]. Among them, compound 319 was an important biosynthetic intermediate.

2.1.11. Cleistanthanes

Three new cleistanthane diterpenoids (325–327) were ioslated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 8 and Table 11. Investigations on the stem bark of C. oblongifolius afforded two new cleistanthanes (325, 326). Among them, compound 326 was a 3,4-seco cleistanthane [93]. One new bis-nor-cleistanthane diterpenoid (327), was found from the twigs and leaves of C. caudatus [94].

2.1.12. Grayananes, Atisanes, Phytanes, Laevinanes and Meroditerpenoids

From the leaves of C. tonkinensis, two new rare grayanane diterpenoids, crotonkinensins A (328) and B (329), were isolated [100]. Two new 3,4-seco atisane diterpenoids, crotobarin (330) from C. barorum and crotogoudin (331) from C. goudotii, were found [101]. Investigations on the aerial parts of C. laui gave two new phytane diterpenoids (332, 333) [37]. Two new laevinane diterpenoids, crolaevinoid G (334) and H (335), were obtained [39]. Two new meroditerpenoids, steenkrotin A (336) and B (337), containing new carbon skeletons, were isolated from the leaves of C. steenkampianus [102]. From the the roots of C. crassifolius, two new meroditerpenoids, norcrassin A (338) and cracroson D (339), were reported [35,69]. Among them, norcrassin A (338) possessing a new carbon skeleton with a 5/5/5/6 tetracyclic system, was a C16 tetranorditerpenoid, while cracroson D (339) featured a new skeleton with a rare cyclobutane ring. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 9 and Table 12, Table 13, Table 14, Table 15 and Table 16.

2.2. Sesquiterpenoids, Sesterterpenoids and Triterpenoids

Seven new sesquiterpenoids (340–346), one sesterterpenoid (347) and one triterpenoid (348) were ioslated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are summarized in Figure 10 and Table 17, Table 18 and Table 19. From C. muscicarpa, one new patchoulane sesquiterpenoid (340) was obtained [103]. A guaiane sesquiterpenoid (341) was isolated from C. regelianus [94]. Investigations on the leaves of C. pedicellatus afforded a bis-nor-sesquiterpenoid (342) [104]. Two rare sesquiterpenoid, Crocrassins A (343) and B (344) having cyclopropylcyclopentane moiety, were reported [105]. Other two sesquiterpenoids, 1,3,5-cadinatriene-(7R,10S)-diol (345) and cracroson H (346) were found from C. dichogamus [75], and C. crassifolius [40], respectively. One rare sesterterpenoid, pseudopulchellol (347), was isolated from the leaves of C. pseudopulchellus [106]. From the root of C. bonplandianum, a new ursane triterpenoid (348) was obtained [107].

2.3. Glycosides

Twenty-one new glycosides (349–369) were ioslated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 11 and Table 20. From C. crassifolius, a patchoulane sesquiterpenoid glycoside (349), an isocrotofolane glucoside (368), and a phenolic glycoside (369) were reported [69,108]. Compound 350, isolated from C. lachnocarpus, was the first triterpenoid glucoside reported from the genus Croton [109]. A new flavone glucoside (351) was found from the leaves of C. zambesicus [110]. Investigations on the leaves of C. cascarilloides and C. oblongifolius afforded 13 new megastigmane glycosides, crotonionosides A–G (352–358) and Oblongionosides A–F (359–364) [111,112]. One new bis-nor-sesquiterpenoid glycoside (365) was isolated from C. pedicellatus [104]. One new diglyceride galactoside (366) and one new clerodane glucoside (367) were obtained from C. sparsiorus [113], and C. limae [35], respectively.

2.4. Alkaloids

Eight new alkaloids (370–377) were reported from Croton species. Their structures, molecular formula, names, corresponding sources, and references are listed in Figure 12 and Table 21. From C. sparsiflorus, two new amide alkaloids crotamides A (370) and B (371), and one new proaporphine alkaloid, crotsparsidine (374) were isolated [96,114]. One new pyrazine derivative, crotonine (372) was obtained from the leaves of C. tiglium [97]. Investigations on C. cascarilloides afforded a new glutarimide alkaloid, crotonimide C (375) [42]. Other three new alkaloids (373, 376–377) were found from C. pullei, C. heliotropiifolius, and C. echioides, respectively [115,116,117].

2.5. Benzoate Derivatives, Pyran-2-One Derivatives, Cyclicpeptides, Tropone Derivatives and Limonoids

Three benzoate derivatives (378–380) were isolated from C. sylvaticus and C. hutchinsonianus [118,119]. Investigations on C. crassifolius afforded three new pyran-2-one derivatives, crotonpyrone A (381), B (382) and C (383) [120,121]. Two cyclicpeptides (384, 385) were obtained from C. gossypifolius and C. urucurana [122,123], while two tropone derivatives (386, 387) were isolated from C. zehntneri and C. argyroglossum [124,125]. From the root bark of C. jatrophoides, two new limonoids, musidunin (388) and musiduol (389), were found [126]. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 13 and Table 22, Table 23, Table 24, Table 25 and Table 26.

2.6. Miscellaneous Compounds

Flavonoids, lignans, and other types of 10 compounds were also isolated from Croton species. Their structures, molecular formula, names, corresponding sources, and references are collected in Figure 13 and Table 27. From the stems of C. caudatus, one new flavone, crotoncaudatin (390), was isolated [127]. A new nor-lignan (391) was obtained from the twigs and leaves of C. kongensis [67]. Investigations on C. laevifolius gave two new prenylated dihydrostilbenes, laevifolin A (393), B (394) and one new aromatic compound (399) [89,128]. A long chain linear ester, lobaceride (392) was isolated from the twigs and leaves of C. lobatus [129]. One indanone derivative (395) was found from the leaves of C. steenkampianus [102], while a trisubstituted furan derivative (396) was isolated from the bark of C. oblongifolius [22]. From C. sparsiflorus, an inositol, sparsifol (397), and a sphingolipid, sparsioamide (398), were obtained [96,113].

Go to:

3. Biological Activities

Compounds isolated from Croton species exert a wide range of biological activities, including cytotoxic, anti-inflammatory, antifungal, acetylcholinesterase inhibitory, and neurite outgrowth-promoting activities.

3.1. Cytotoxic Activity

The anti-tumor activity of many plants from the Croton species have been reported. Therefore, the cytotoxicity of the isolated compounds is the most commonly studied bioactivity. The cytotoxic activities of the isolated compounds from the Croton species are listed in Table 28. Four new tigliane diterpene esters (135–137, 139) from the leaves of C. tiglium, exhibited most potent cytotoxic activity against K562 cell line with IC₅₀ values of 0.03, 0.03, 0.07 and 0.05 μM, respectively [51].

Table 28

Cytotoxic activity of compounds from the genus Croton.

Compounds	Tumor Cell Line	Activity (IC₅₀)	Ref
Methyl 15,16-epoxy-3,13(16),14-ent-clerodatrien-18,19-olide-17-carboxylate (6)	HuCCA-1	36.0 μg/mL	[29]
	KB	26.0 μg/mL	[29]
	HeLa	30.0 μg/mL	[29]
	MDA-MB231	29.0 μg/mL	[29]
	T47D	10.0 μg/mL	[29]
Dimethyl-15,16-epoxy-12-oxo-3,13 (16)14-ent-clerodatriene-17,18-dicarboxylate (7)	HuCCA-1	39.0 μg/mL	[29]
	KB	27.0 μg/mL	[29]
	HeLa	29.0 μg/mL	[29]
	MDA-MB231	27.0 μg/mL	[29]
	T47D	25.0 μg/mL	[29]
Laevigatbenzoate (8)	HeLa	45.4 μM	[13]
Crotonolide A (23)	HL-60	9.42 μM	[21]
	P-388	7.45 μM	[21]
15-oxo-17(10′-α-pinenyl)-kauran-18-oic acid (181)	HCT-116	7.14 μg/mL	[35]
	OVCAR-8	8.19 μg/mL	[35]
	SF-295	>10.0 μg/mL	[35]
Launine K (67)	HeLa	14.5 μM	[37]
	MCF-7	62.5 μM	[37]
Crassin H (75)	HL-60	11.8 ± 2.1 μM	[17]
	A549	5.2 ± 0.4 μM	[17]
Crassifolius A (76)	Hep3B	17.91 μM	[38]
	HepG2	42.04 μM	[38]
Cracroson D (339)	T24	14.48 ± 0.65 μM	[40]
	A549	25.64 ± 2.14 μM	[40]
Cracroson E (87)	T24	22.99 ± 1.76 μM	[40]
	A549	51.88 ± 14.07μM	[40]
	Hela	3.9 μM	[48]
	DU145	7.2 μM	[48]
	A549	5.8 μM	[48]
	SGC-7091	13 μM	[48]
	H1975	10 μM	[48]
	HL60	12 μM	[48]
	293T	291.6 μM	[48]
	LX-2	>500.0 μM	[48]
12-O-benzoylphorbol-13-(2-methyl)butyrate (114)	K562	15 μM	[48]
	MOLT-4	12 μM	[48]
	U937	17 μM	[48]
	MCF-7	20 μM	[48]
	Hela	4.6 μM	[48]
	DU145	4.3 μM	[48]
	A549	6.9 μM	[48]
	SGC-7091	10 μM	[48]
	H1975	3.3 μM	[48]
	HL60	6.8 μM	[48]
	293T	420.4 μM	[48]
	LX-2	>500.0 μM	[48]
12-O-tiglyl-7-oxo-5-ene-phorbol-13-(2-methyl)butyrate (115)	K562	17 μM	[48]
	MOLT-4	4.8 μM	[48]
	U937	21 μM	[48]
	MCF-7	20 μM	[48]
	Hela	5.0 μM	[48]
	DU145	10 μM	[48]
	A549	19 μM	[48]
	SGC-7091	23 μM	[48]
	H1975	10 μM	[48]
	HL60	10 μM	[48]
	293T	455.3 μM	[48]
	LX-2	>500.0 μM	[48]
13-O-(2-metyl)butyryl-4-deoxy-4a-phorbol (116)	K562	8.0 μM	[48]
	MOLT-4	9.9 μM	[48]
	U937	18 μM	[48]
	MCF-7	24 μM	[48]
	H1975	10 μM	[48]
	HL60	10 μM	[48]
	293T	455.3 μM	[48]
	LX-2	>500.0 μM	[48]
	Hela	10 μM	[48]
	DU145	10 μM	[48]
	A549	4.5 μM	[48]
	SGC-7091	5.4 μM	[48]
	H1975	3.3 μM	[48]
	HL60	9.8 μM	[48]
	293T	191.0 μM	[48]
	LX-2	>500.0 μM	[48]
Crotignoid A (117)	HL-60	1.61 μM	[49]
	A549	2.85 μM	[49]
Crotignoid B (118)	HL-60	22.1 μM	[49]
	A549	31.0 μM	[49]
Crotignoid C (119)	HL-60	32.3 μM	[49]
	A549	5.03 μM	[49]
Crotignoid D (120)	HL-60	19.8 μM	[49]
	A549	10.2 μM	[49]
Crotignoid F (122)	HL-60	44.6 μM	[49]
	A549	6.96 μM	[49]
Crotignoid G (123)	HL-60	22.1 μM	[49]
	A549	3.89 μM	[49]
Crotignoid H (124)	HL-60	9.97 μM	[49]
	A549	8.08 μM	[49]
Crotignoid I (125)	HL-60	14.8 μM	[49]
	A549	24.4 μM	[49]
Crotignoid J (126)	HL-60	14.2 μM	[49]
	A549	29.5 μM	[49]
Crotusin A (128)	HL-60	12.53 ± 0.37 μM	[44]
	SMMC-7721	7.06 ± 0.72 μM	[44]
	A549	9.69 ± 0.41 μM	[44]
	MCF-7	9.56 ± 0.76 μM	[44]
	SW480	14.88 ± 0.43 μM	[44]
Crotusin B (129)	HL-60	19.39 ± 0.46 μM	[44]
	SMMC-7721	21.13 ± 0.29 μM	[44]
	A549	14.66 ± 1.66 μM	[44]
	MCF-7	1.49 ± 0.23 μM	[44]
	SW480	31.21 ± 3.20 μM	[44]
Crotusin C (130)	HL-60	4.19 ± 0.15 μM	[44]
	SMMC-7721	3.87 ± 0.12 μM	[44]
	A549	2.44 ± 0.35 μM	[44]
	MCF-7	0.49 ± 0.04 μM	[44]
	SW480	2.89 ± 0.01 μM	[44]
12-O-tiglylphorbol-4-deoxy-4β-phorbol-13-acetate (131)	SNU387	59.5 ± 2.1 μM	[50]
	SNU398	43.7 ± 1.5 μM	[50]
12-O-tiglylphorbol-4-deoxy-4β-phorbol-13-hexadecanoate (132)	SNU387	30.2 ± 1.4 μM	[50]
	SNU398	91.2 ± 3.7 μM	[50]
13-O-acetylphorbol-4-deoxy-4β-phorbol-20-oleate (133)	SNU387	1.9 ± 0.2 μM	[50]
	SNU398	13.5 ± 1.1 μM	[50]
13-O-acetylphorbol-4-deoxy-4β-phorbol-20-linoleate (134)	SNU387	0.71 ± 0.08 μM	[50]
	SNU398	18.2 ± 1.7 μM	[50]
4-deoxy-20-oxophorbol 12-tiglyl 13-acetate (135)	K562	0.03 μM	[51]
	A549	6.88 μM	[51]
	Huh-7	3.85 μM	[51]
7-oxo-5-ene-phorbol-13-(2-methylbutyrate) (136)	K562	0.03 μM	[51]
	A549	6.33 μM	[51]
	Huh-7	20.9 μM	[51]
7-hydroxyl-phorbol-5-ene-13-(2-methyl)butyrate (137)	K562	0.07 μM	[51]
	A549	8.86 μM	[51]
	Huh-7	11.6 μM	[51]
13-O-(2-metyl)butyryl-phorbol (139)	K562	0.05 μM	[51]
	A549	43.5 μM	[51]
	Huh-7	34.2 μM	[51]
7-keto-12-O-tiglylphorbol-13-acetate (140)	HL-60	6.22 ± 3.24 μg/mL	[52]
	A549	18.0 ± 9.48 μg/mL	[52]
Phorbol-13-isobutyrate (148)	HL-60	0.22 ± 0.15 μg/mL	[52]
14-epi-hyalic acid (159)	HL-60	8.2 μM	[63]
Kongeniod A (178)	HL-60	1.27 ± 0.24 μM	[59]]
	A549	5.74 ± 0.25 μM	[59]
Kongeniod B (179)	HL-60	0.47 ± 0.04 μM	[59]
	A549	3.25 ± 0.91 μM	[59]
Kongeniod C (180)	HL-60	0.58 ± 0.17 μM	[59]
Crotonkinensin D (188)	MCF-7	9.4 ± 1.7 μM	[61]
	MCF-7/TAMR	2.6 ± 0.9 μM	[61]
	MCF-7/ADR	18.9 ± 0.6 μM	[61]
	MDA-MB-231	22.0 ± 0.9 μM	[61]
EBC-162 (207)	HL-60	15 μg/mL	[74]
	HT29	15 μg/mL	[74]
	MCF-7	30 μg/mL	[74]
	MM96	10 μg/mL	[74]
	NNF	20 μg/mL	[74]
	K562	50 μg/mL	[74]
EBC-233 (208)	HL-60	10 μg/mL	[74]
	HT29	80 μg/mL	[74]
	MCF-7	20 μg/mL	[74]
	MM96	6 μg/mL	[74]
	NNF	50 μg/mL	[74]
	K562	50 μg/mL	[74]
EBC-300 (209)	HL-60	35 μg/mL	[74]
	HT29	100 μg/mL	[74]
	MCF-7	100 μg/mL	[74]
	MM96	80 μg/mL	[74]
	NNF	80 μg/mL	[74]
	K562	100 μg/mL	[74]
EBC-240 (210)	HL-60	45 μg/mL	[74]
	HT29	80 μg/mL	[74]
	MCF-7	50 μg/mL	[74]
	MM96	12 μg/mL	[74]
	NNF	80 μg/mL	[74]
	K562	60 μg/mL	[74]
EBC-241 (211)	HL-60	40 μg/mL	[74]
	HT29	80 μg/mL	[74]
	MCF-7	40 μg/mL	[74]
	MM96	12 μg/mL	[74]
	NNF	75 μg/mL	[74]
	K562	60 μg/mL	[74]
Furanocembranoid 1 (266)	BT474	7.8 μg/mL	[83]
	CHAGO	7.0 μg/mL	[83]
	Hep-G2	5.6 μg/mL	[83]
	KATO-3	5.9 μg/mL	[83]
	SW-620	6.3 μg/mL	[83]
Furanocembranoid 2 (267)	BT474	9.5 μg/mL	[83]
	CHAGO	>10 μg/mL	[83]
	Hep-G2	>10 μg/mL	[83]
	KATO-3	6.8 μg/mL	[83]
	SW-620	9.9 μg/mL	[83]
Furanocembranoid 3 (268)	BT474	9.6 μg/mL	[83]
	CHAGO	7.1 μg/mL	[83]
	Hep-G2	5.7 μg/mL	[83]
	KATO-3	8.2 μg/mL	[83]
	SW-620	5.6 μg/mL	[83]]
Furanocembranoid 4 (269)	BT474	9.6 μg/mL	[83]
	CHAGO	9.3 μg/mL	[83]
	Hep-G2	6.1 μg/mL	[83]
	KATO-3	8.1 μg/mL	[83]
	SW-620	6.0 μg/mL	[83]
Laevigatlactone B (272)	Hela	38.4 μM	[84]
(+)-[1R,2S,7S,8S,12R]-7,8-Epoxy-2,12-cyclocembra-3E,10Zdien-20,10-olide (276*)	PEO1	132 nM	[85]
	PEO1TaxR	200 nM	[85]
(+)-[1R,4S,10R]-4-Hydroxycembra-2E,7E,11Z-trien-20,10-olide (278*)	PEO1	125 nM	[85]
	PEO1TaxR	135 nM	[85]
Crotontomentosin A (294)	Hela	24.0 ± 2.6 μM	[88]
	Hep G2	87.9 ± 4.5 μM	[88]
	MDA-MB-231	54.1 ± 2.1 μM	[88]
	A549	40.6 ± 3.9 μM	[88]
Crotontomentosin B (295)	Hela	>100 μM	[88]
	Hep G2	28.1 ± 2.1 μM	[88]
	MDA-MB-231	28.7 ± 3.4 μM	[88]
	A549	29.1 ± 5.2 μM	[88]
Crotontomentosin C (297)	Hela	47.9 ± 3.3 μM	[88]
	Hep G2	83.3 ± 5.3 μM	[88]
	MDA-MB-231	>100 μM	[88]
	A549	>100 μM	[88]]
Crotontomentosin D (296)	Hela	59.7 ± 4.5 μM	[88]
	Hep G2	>100 μM	[88]
	MDA-MB-231	49.3 ± 2.8 μM	[88]
	A549	>100 μM	[88]
Crotolaevigatone B (300)	A549	21.2 μM	[89]
	MDA-MB-231	33.4 μM	[89]
Crotolaevigatone G (305)	A549	25.6 μM	[89]
	MDA-MB-231	32.7 μM	[89]
EBC-324 (311)	MCF-7	40 μM	[92]
	NFF	50 μM	[92]
	K562	6 μM	[92]
EBC-329 (312)	MCF-7	13 μM	[92]
	NFF	40 μM	[92]
	K562	0.6 μM	[92]
ent-3β-hydroxypimara-8(14),9,15-trien-12-one (319)	NFF	23 μg/mL	[98]
	Hela	13 μg/mL	[98]
	HT 29	13 μg/mL	[98]
	MCF-7	16 μg/mL	[98]
	MM96L	2.8 μg/mL	[98]
	K562	17 μg/mL	[98]
EBC-325 (321)	MCF-7	20 μM	[99]
	NFF	6 μM	[99]
	K562	3 μM	[99]
EBC-326 (322)	MCF-7	14 μM	[99]
	NFF	6 μM	[99]
	K562	6 μM	[99]
EBC-327 (323)	MCF-7	10 μM	[99]
	NFF	10 μM	[99]
	K562	10 μM	[99]
3-hydroxycleistantha-13(17),15-diene (325)	KATO-3	6.0 μg/mL	[93]
	SW-620	>10 μg/mL	[93]
	BT474	6.1 μg/mL	[93]
	Hep-G2	0.5 μg/mL	[93]
	CHAGO	5.5 μg/mL	[93]
3,4-seco-cleistantha-4(18),13(17),15-trien-3-oic acid (326)	KATO-3	9.6 μg/mL	[93]
	SW-620	>10 μg/mL	[93]
	BT474	10 μg/mL	[93]
	Hep-G2	8.6 μg/mL	[93]
	CHAGO	>10 μg/mL	[93]
Crotobarin (330)	KB	2.5 ± 0.10 μM	[101]
	HT29	2.1 ± 0.60 μM	[101]
	A549	0.79 ± 0.15 μM	[101]
	HL60	0.56 ± 0.02 μM	[101]
Crotogoudin (331)	KB	1.5 ± 0.03 μM	[101]
	HT29	1.9 ± 0.25 μM	[101]
	A549	0.54 ± 0.02 μM	[101]
	HL60	0.49 ± 0.01 μM	[101]
Crotonpyrone A (381)	Hela	10.21 μg/mL	[120]
	NCI-446	6.59 μg/mL	[120]
Crotonpyrone B (382)	Hela	9.54 μg/mL	[120]
[1−9-NαC]-crourorb A1 (385)	NCI-ADR/RES	4.8 μM	[123]

3.2. Anti-Inflammatory Activity

Bioassay-guided fractionation of the aerial parts of C. ciliatoglandulifer led to the isolation of tigliane diterpenoids 95, 97, which inhibited the enzymes cyclooxygenases-1 (IC₅₀, 0.001, and 1.0 μM, respectively) and cyclooxygenases-2 (IC₅₀, 2.2 μM, for compound 95) [41]. A tigliane diterpenoid (114) was isolated from the branches and leaves of C. tiglium, which displayed moderate inhibition of the enzymes COX-1 and COX-2, with IC₅₀ values of 0.14 and 8.5 μM, respectively [48]. crotonkinin A (157), isolated from C. tonkinensis, showed anti-inflammatory effect on LPS-induced iNOS-dependent NO production and NOX-dependent ROS production in microglial cells (IC₅₀, 46.2 ± 3.1 μM in NOS; maximum inhibition of NOX activity at 50 μM, 11.2%) [62]. Eight ent-kauranes (169–176) from C. tonkinensis exhibited the anti-inflammatory potential for inhibition of superoxide Anion generation and elastase release. Among them, crotonkinins F (172) displayed significant inhibition of superoxide anion generation (IC₅₀, 2.88 ± 0.52 μM) and elastase release (IC₅₀, 4.44 ± 1.45 μM) [66]. Labdane diterpenoids 251, 254 and 257, 258, isolated from the aerial parts of C. laui, were found to show anti-inflammatory activities in LPS-stimulated RAW 264.7 cells with IC₅₀ values in the range 42.73–93.04 μM [82]. Two grayanane diterpenoids, crotonkinensins A (328) and B (329) from the leaves of C. tonkinensis, were reported to decrease the LPS-induced COX-2 promoter activity in Raw 264.7 cells with IC₅₀ values of 7.14 ± 0.2 and 5.49 ± 0.2 μM, respectively [100]. Two benzoate derivatives (379, 380) were obtained from C. hutchinsonianus. Compound 379 showed significant activity against COX-1 (IC₅₀, 4.95 ± 0.58 μg/mL) and COX-2 (IC₅₀, 2.11 ± 1.3 μg/mL), while compound 380 (IC₅₀, 1.88 ± 0.17 μg/mL) preferentially inhibited COX-2 [119].

3.3. Antifungal Activity

Two benzoate derivatives (379–380) were isolated from C. hutchinsonianus, and exhibited antifungal activity against Candida albicans (IC₅₀, 11.41 ± 1.44, and 5.36 ± 0.01 μg/mL, respectively) [119]. Ursane triterpenoid (348) from the root of C. bonplandianum, displayed the antifungal activity against Calletotricheme camellie (IC₅₀, 10 μg/mL), Fussarium equisitae (IC₅₀, <15 μg/mL), Alterneria alternata (IC₅₀, 10 μg/mL), Curvularia eragrostidies (IC₅₀, <10 μg/mL) and Colletorichum gloeosporiodes (IC₅₀, 15 μg/mL) [107].

3.4. Acetylcholinesterase Inhibitory Activity

An indole alkaloid derivative 376, isolated from the leaves of C. heliotropiifolius, exhibited the acetylcholinesterase inhibitory activity with IC₅₀ values of 17.8 ± 0.6 μM [116]. Compund 378 from C. sylvaticus, also displayed the same activity [118].

3.5. Neurite Outgrowth-Promoting Activity

Two clerodane diterpenoids, crotonpenes A (36) and B (37) were isolated from C. yanhuii, which markedly increased the NGF (20 ng/mL)-induced proportion of neurite bearing cells by 59%, and 47% at 15 μM, respectively [23]. Crotoeurins A–C (40–42) obtained from C. euryphyllus, were found to display neurite outgrowth-promoting activity on NGF mediated PC12 cells at concentration of 10 μM. The percentages of neurite-bearing cells were 9.72%, 14.90%, and 7.14%, respectively [25].

3.6. Other Activities

Besides the above activities, other biological activities have also been reported. Crotonolide G (32), from the aerial parts of C. laui, was found to exhibit potent antibacterial activity (MIC, 43.4 μM) against four strains of Gram-positive bacteria, namely, Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, and Bacillus subtilis [21]. Crassifolin H (39) was obtained from roots of C. crassifolius as an angiogenic inhibitor by reducing vessel formation to 59.3% at 15 μg/mL [34]. Tigliane diterpene (111) was isolated from the leaves of C. mauritianus, which inhibited chikungunya virus-induced cell death in cell culture with EC₅₀s of 4.0 ± 0.8 μM [43]. The leaves of C. tiglium yielded two tigliane diterpenoids (135, 136), which displayed significant antitubercular activities with MIC values of 19.5, and 20.9 μM, respectively [51]. Compounds (162–165) were four ent-kaurane diterpenes from C. tonkinensis, which significantly stimulated differentiation in osteoblasts [64]. From the twigs and leaves of C. cascarilloides, two crotofolane diterpenoid alkaloids cascarinoids B–C (226, 227) were obtained, both of which displayed moderate activities against the ConA-induced proliferation of T lymphocyte cells and/or LPS-induced proliferation of B lymphocyte cells with IC₅₀ values ranging from 6.14 to 16.27 μM [71]. Meroditerpenoid (336), from C. steenkampianus, showed antiplasmodial activities of 15.8 (D10), 9.1 (W2), and 9.4 (Dd2) μM [102]. Indole alkaloid (377) was found in C. mauritianus with antioxidant activity (IC₅₀, 30.0.0 ± 0.7 μM) by the DPPH radical scavenging assay [117]. Bioactivity-guided fractionation of the root bark of C. jatrophoides resulted in the isolation of musidunin (388) and musiduol (389), both of which showed insect antifeedant activities (PC₅₀, 3 μg/mL, PC₉₅, 10 μg/mL; PC₅₀, 4 μg/mL, PC₉₅, 20 μg/mL, respectively) against the second-instar larvae of Pectinophora gossypiella in a leaf disk assay [126].

Go to:

4. Conclusions

In the present review, we systematically summarized the chemical constituents and biological activity studies of Croton species covering from 2006 to 2018. To date, a total of 399 new compounds were reported from Croton species, which included 339 diterpenoids, seven sesquiterpenoids, 21 glycosides, eight alkaloids, and 24 miscellaneous compounds (Figure 14). Obviously, diterpenoids are characteristic components for Croton species. The diterpenoids with clerodane, tigliane, kaurane, crotofolane, labdane, and cembrane skeletons are among the most studied diterpenoids isolated from Croton species (Figure 14). Although the current studies have shown that these isolated compounds from Croton species possessed diversified biological activities, many compounds have never been biologically tested. Moreover, most studies conducted so far have focused mainly on in vitro cytotoxic assays. Further studies on the mechanism of actions and the structure activity relationship are needed in order to provide a better understanding of the chemical constituents from Croton species as potential medicines. Increasing interest in the chemistry and pharmaceutics of Croton species may promote new progress in finding and developing novel compounds.

An external file that holds a picture, illustration, etc.
Object name is molecules-23-02333-g014.jpg

Figure 14

The percentage of each type of compounds (left), the percentage of each type of diterpenoids (right) from Croton Species.

Go to:

Author Contributions

W.-H.X. classified the chemical constituents and drafted the structural formulas, wrote the manuscript; W-Y L. collected literatures; Q.L. managed references, overall responsibility.

Go to:

Funding

We are thankful for financial supports from the Natural Science Foundation of China (NSFC) (21362035); The Initial Foundation of Scientific Research for the introduction of talents from Southwest Forestry University for Wen-Hui Xu (20130916); and Opening Research Foundation from Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University (KLE201807).

Go to:

Conflicts of Interest

The authors declare no conflict of interest.

Go to:

Footnotes

Sample Availability: Samples of the compounds are not available from the authors.

Go to:

References

1. Salatino A., Salatino M.L.F., Negri G. Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae) J. Braz. Chem. Soc. 2007;18:11–33. 10.1590/S0103-50532007000100002. [CrossRef] [Google Scholar]

2. Júnior S.F.P., Conserva L.M., Filho J.M.B. Clerodane diterpenes from Croton species: Distribution and a compilation of their ¹³C-NMR spectral data. Nat. Prod. Commun. 2006;1:319–344. [Google Scholar]

3. Wu X.A., Zhao Y.M. Advance on chemical composition and pharmacological action of Croton L. Nat. Prod. Res. Dev. 2004;16:467–472. [Google Scholar]

4. Nath R., Roy S., De B., Choudhury M.D. Anticancer and antioxidant activity of Croton: A review. Int. J. Pharm. Pharm. Sci. 2013;5:63–70. [Google Scholar]

5. Premprasert C., Tewtrakul S., Plubrukarn A., Wungsintaweekul J. Anti-inflammatory activity of diterpenes from Croton stellatopilosus on LPS-induced RAW264. 7 cells. J. Nat. Med. 2013;67:174–181. 10.1007/s11418-012-0668-5. [Abstract] [CrossRef] [Google Scholar]

6. Maroyi A. Ethnopharmacological uses, phytochemistry, and pharmacological properties of Croton macrostachyus Hochst. Ex Delile: A Comprehensive Review. Evid Based. Compl. Alt. 2017;20:1–17. 10.1155/2017/1694671. [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]

7. Maroyi A. Ethnomedicinal uses and pharmacological activities of Croton megalobotrys Müll Arg: A systematic review. Trop. J. Pharm. Res. 2017;16:2535–2543. [Google Scholar]

8. Maroyi A. Traditional usage, phytochemistry and pharmacology of Croton sylvaticus Hochst. ex C. Krauss. Asian Pac. J. Trop. Med. 2017;10:423–429. 10.1016/j.apjtm.2017.05.002. [Abstract] [CrossRef] [Google Scholar]

9. Dutta S., Chaudhuri T.K. Pharmacological aspect of Croton bonplandianus Baill: A comprehensive review. J. Pharmacogn. Phytochem. 2018;7:811–813. [Google Scholar]

10. Ghosh T., Biswas M.K., Roy P., Guin C. A review on traditional and pharmacological uses of Croton bonplandianum with special reference to phytochemical aspect. Eur. J. Med. Plant. 2018;22:1–10. 10.9734/EJMP/2018/40697. [CrossRef] [Google Scholar]

11. Li R., Morris-Natschke S.L., Lee K.H. Clerodane diterpenes: Sources, structures, and biological activities. Nat. Prod. Rep. 2016;33:1166–1226. 10.1039/C5NP00137D. [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]

12. Ndunda B., Langat M.K., Midiwo J.O., Omosa L.K. Diterpenoid derivatives of Kenyan croton sylvaticus. Nat. Prod. Commun. 2015;10:557–578. [Abstract] [Google Scholar]

13. Zou G.A., Zhang H.W., Aisa H.A., Yang J.S., Peng C.Z., Zou Z.M. Laevigatbenzoate from Croton laevigatus vahl. J. Nat. Med. 2011;65:391–394. 10.1007/s11418-010-0503-9. [Abstract] [CrossRef] [Google Scholar]

14. Hu Y., Zhang L., Wen X.Q., Zeng X.J., Rui W., Cen Y.Z. Two new diterpenoids from croton crassifolius. J. Asian. Nat. Prod. Res. 2012;14:785–788. 10.1080/10286020.2012.694872. [Abstract] [CrossRef] [Google Scholar]

15. García A., Ramírez-Apan T., Cogordan J.A., Delgado G. Absolute configuration assignments by experimental and theoretical approaches of ent-labdane-and cis-ent-clerodane-type diterpenes isolated from Croton glabellus. Can. J. Chem. 2006;84:1593–1602. 10.1139/v06-164. [CrossRef] [Google Scholar]

16. Wang G.C., Li J.G., Li G.Q., Xu J.J., Wu X., Ye W.C., Li Y.L. Clerodane diterpenoids from Croton crassifolius. J. Nat. Prod. 2012;75:2188–2192. 10.1021/np300636k. [Abstract] [CrossRef] [Google Scholar]

17. Yuan Q.Q., Tang S., Song W.B., Wang W.Q., Huang M., Xuan L.J. Crassins A-H, diterpenoids from the roots of Croton crassifolius. J. Nat. Prod. 2017;80:254–260. 10.1021/acs.jnatprod.6b00425. [Abstract] [CrossRef] [Google Scholar]

18. Guetchueng S.T., Nahar L., Ritchie K.J., Ismail F.M.D., Evans A.R., Sarker S.D. Ent-clerodane diterpenes from the bark of Croton oligandrus Pierre ex Hutch. and assessment of their cytotoxicity against human cancer cell lines. Molecules. 2018;23:410. 10.3390/molecules23020410. [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]

19. Yamale S.C., Koudou J., Samb A., Heitz A., Teulade J.C. Structural elucidation of a new furoclerodane from stem barks of croton mayumbensis J. Leonard extracts. Int. J. Phys. Sci. 2009;4:96–100. [Google Scholar]

20. Wang G.C., Zhang H., Liu H.B., Yue J.M. Laevinoids A and B: Two diterpenoids with an unprecedented backbone from Croton laevigatus. Org. Lett. 2013;15:4880–4883. 10.1021/ol402318m. [Abstract] [CrossRef] [Google Scholar]

21. Liu C.P., Xu J.B., Zhao J.X., Xu C.H., Dong L., Ding J., Yue J.M. Diterpenoids from Croton laui and their cytotoxic and antimicrobial activities. J. Nat. Prod. 2014;77:1013–1020. 10.1021/np500042c. [Abstract] [CrossRef] [Google Scholar]

22. Pudhom K., Sommit D. Clerodane diterpenoids and a trisubstituted furan from Croton oblongifolius. Phytochem. Lett. 2011;4:147–150. 10.1016/j.phytol.2011.02.004. [CrossRef] [Google Scholar]

23. Sun Y., Wang M., Ren Q., Li S., Xu J., Ohizumi Y., Xie C., Jin D.Q., Guo Y. Two novel clerodane diterpenenes with NGF-potentiating activities from the twigs of Croton yanhuii. Fitoterapia. 2014;95:229–233. 10.1016/j.fitote.2014.03.012. [Abstract] [CrossRef] [Google Scholar]

24. Velázquez-Jiménez R., Vargas-Mendoza D., Gayosso-de-Lucio J.A., González-Montiel S., Villagómez-Ibarra J.R. Three novel epoxy-clerodanes bearing a furan ring from Croton hypoleucus. Phytochem. Lett. 2018;24:21–26. 10.1016/j.phytol.2018.01.001. [CrossRef] [Google Scholar]

25. Pan Z., Ning D., Wu X., Huang S., Li D., Lv S. New clerodane diterpenoids from the twigs and leaves of Croton euryphyllus. Bioorg. Med. Chem. Lett. 2015;46:329–1332. 10.1016/j.bmcl.2015.01.033. [Abstract] [CrossRef] [Google Scholar]

26. Qiu M., Cao D., Gao Y., Li S., Zhu J., Yang B., Zhou L., Zhou Y., Jin J., Zhao Z. New clerodane diterpenoids from Croton crassifolius. Fitoterapia. 2016;108:81–86. 10.1016/j.fitote.2015.11.016. [Abstract] [CrossRef] [Google Scholar]

27. Ndunda B., Langat M.K., Mulholland D.A., Eastman H., Jacob M.R., Khan S.I., Walker L.A., Muhammad I., Kerubo L.O., Midiwo J.O. New ent-Clerodane and abietane diterpenoids from the Roots of Kenyan Croton megalocarpoides Friis & M. G. Gilbert. Planta Med. 2016;82:1079–1086. [Abstract] [Google Scholar]

28. Zhang Z.X., Li H.H., Fan G.X., Li Z.Y., Dong L.L., Li H.Y., Fei D.Q. A novel norclerodane diterpenoid from the roots of Croton crassifolius. Nat. Prod. Commun. 2015;10:1917–1918. [Abstract] [Google Scholar]

29. Youngsa-ad W., Ngamrojanavanich N., Mahidol C., Ruchirawat S., Prawat H., Kittakoop P. Diterpenoids from the roots of Croton oblongifolius. Planta Med. 2007;73:1491–1494. 10.1055/s-2007-990247. [Abstract] [CrossRef] [Google Scholar]

30. Mbwambo Z., Foubert K.M., Kapingu M., Magadula J., Moshi M., Lemiere F., Goubitz K., Fraanje J., Peschar R., Vlietinck A., et al. New furanoditerpenoids from croton jatrophoides. Planta Med. 2008;75:262–267. 10.1055/s-0028-1088383. [Abstract] [CrossRef] [Google Scholar]

31. Brasil D.S.B., Müller A.H., Guilhon G.M.S.P., Alves C.N., Peris G., Llusard R., Moliner V. Isolation, X-ray crystal structure and theoretical calculations of the new compound 8-Epicordatin and identification of others terpenes and steroids from the bark and leaves of Croton palanostigma klotzsch. J. Braz. Chem. Soc. 2010;21:731–739. 10.1590/S0103-50532010000400021. [CrossRef] [Google Scholar]

32. Pizzolatti M.G., Bortoluzzi A.J., Brighente I.M.C., Zuchinalli A., Carvalho F.K., Candido A.C.S., Peresb M.T.L.P. Clerodane diterpenes from bark of Croton urucurana Baillon. J. Braz. Chem. Soc. 2013;24:609–614. [Google Scholar]

33. Abega D.F., Kapche D.W., Ango P.Y., Mapitse R., Yeboah S.O., Ngadjui B.T. Chemical constituents of croton oligandrum (euphorbiaceae) Z. Naturforsch. C. 2014;69:181–185. 10.5560/znc.2013-0207. [Abstract] [CrossRef] [Google Scholar]

34. Huang W.H., Li G.Q., Li J.G., Wu X., Ge W., Chung H.Y., Ye W.C., Li Y.L., Wang G.C. Two new clerodane diterpenoids from Croton crassifolius. Heterocycles. 2014;89:1585–1593. [Google Scholar]

35. Sousa A.H., Junior J.N.S., Guedes M.L.S., Braz-Filho R., Costa-Lotufo L.V., Araujo A.J., Silveira E.R., Lima M.A.S. New terpenoids from Croton limae (Euphorbiaceae) J. Braz. Chem. Soc. 2015;26:1565–1572. [Google Scholar]

36. Wang J.J., Chung H.Y., Zhang Y.B., Li G.Q., Li Y.L., Huang W.H., Wang G.C. Diterpenoids from the roots of Croton crassifolius and their anti-angiogenic activity. Phytochemistry. 2016;12:270–275. 10.1016/j.phytochem.2015.12.011. [Abstract] [CrossRef] [Google Scholar]

37. Yang L., Zhang Y.-B., Wu Z.-N., Chen N.-H., Jiang S.-Q., Jiang L., Li Y.-L., Wang G.-C. Three new diterpenoids from Croton laui. Chem. Lett. 2016;45:1235–1237. 10.1246/cl.160632. [Abstract] [CrossRef] [Google Scholar]

38. Tian J.L., Yao G.D., Wang Y.X., Gao P.Y., Wang D., Li L.Z., Lin B., Huang X.X., Song S.J. Cytotoxic clerodane diterpenoids from Croton crassifolius. Bioorg. Med. Chem. Lett. 2017;27:1237–1242. 10.1016/j.bmcl.2017.01.055. [Abstract] [CrossRef] [Google Scholar]

39. Zhang J.S., Tang Y.Q., Huang J.L., Li W., Zou Y.H., Tang G.H., Liu B., Yin S. Bioactive diterpenoids from Croton laevigatus. Phytochemistry. 2017;144:151–158. 10.1016/j.phytochem.2017.09.003. [Abstract] [CrossRef] [Google Scholar]

40. Qiu M., Jin J., Zhou L., Zhou W., Liu Y., Tan Q., Cao D., Zhao Z. Diterpenoids from Croton crassifolius include a novel skeleton possibly generated via an intramolecular [2 + 2]-photocycloaddition reaction. Phytochemistry. 2018;145:103–110. 10.1016/j.phytochem.2017.10.008. [Abstract] [CrossRef] [Google Scholar]

41. Rios M.Y., Aguilar-Guadarrama A.B. Nitrogen-containing phorbol esters from Croton ciliatoglandulifer and their effects on cyclooxygenases-1 and-2. J. Nat. Prod. 2006;69:887–890. 10.1021/np0504311. [Abstract] [CrossRef] [Google Scholar]

42. Ndunda B., Langat M.K., Wanjohi J.M., Midiwo J.O., Kerubo L.O. Alienusolin, a new 4α-deoxyphorbol ester derivative, and crotonimide C, a new glutarimide alkaloid from the Kenyan Croton alienus. Planta Med. 2013;79:1762–1766. 10.1055/s-0033-1351044. [Abstract] [CrossRef] [Google Scholar]

43. Corlay N., Delang L., Girard-Valenciennes E., Neyts J., Clerc P., Smadja J., Gueritte F., Leyssen P., Litaudon M. Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus replication. Fitoterapia. 2014;97:87–91. 10.1016/j.fitote.2014.05.015. [Abstract] [CrossRef] [Google Scholar]

44. Chen Y.Y., Yang K.X., Yang X.W., Khan A., Liu L., Wang B., Zhao Y.L., Liu Y.P., Li Y., Luo X.D. New cytotoxic tigliane diterpenoids from Croton caudatus. Planta Med. 2016;82:729–733. 10.1055/s-0042-102539. [Abstract] [CrossRef] [Google Scholar]

45. Jiang L., Zhang Y.B., Jiang S.Q., Zhou Y.D., Luo D., Niu Q.W., Qian Y.R., Li Y.L., Wang G.C. Phorbol ester-type diterpenoids from the twigs and leaves of Croton tiglium. J. Asian Nat. Prod. Res. 2017;19:1191–1197. 10.1080/10286020.2017.1307836. [Abstract] [CrossRef] [Google Scholar]

46. Zhang X.L., Wang L., Li F., Yu K., Wang M.K. Cytotoxic phorbol esters of Croton tiglium. J. Nat. Prod. 2013;76:858–864. 10.1021/np300832n. [Abstract] [CrossRef] [Google Scholar]

47. Ren F.X., Ren F.Z., Yang Y., Yu N.J., Zhang Y., Zhao Y.M. Tigliane diterpene esters from the leaves of Croton tiglium. Helv. Chim. Acta. 2014;97:1014–1019. 10.1002/hlca.201300408. [CrossRef] [Google Scholar]

48. Wang J.F., Yang S.H., Liu Y.Q., Li D.X., He W.J., Zhang X.X., Liu Y.H., Zhou X.J. Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium. Bioorg. Med. Chem. Lett. 2015;25:1986–1989. 10.1016/j.bmcl.2015.03.017. [Abstract] [CrossRef] [Google Scholar]

49. Zhang D.-D., Zhou B., Yu J.-H., Xu C.-H., Ding J., Zhang H., Yue J.-M. Cytotoxic tigliane-type diterpenoids from Croton tiglium. Tetrahedron. 2015;71:9638–9644. 10.1016/j.tet.2015.10.070. [CrossRef] [Google Scholar]

50. Zhang X.-L., Khan A.-A., Wang L., Yu K., Li F., Wang M.-K. Four new phorbol diesters from Croton tiglium and their cytotoxic activities. Phytochem. Lett. 2016;16:82–86. 10.1016/j.phytol.2016.03.008. [CrossRef] [Google Scholar]

51. Zhao B.Q., Peng S., He W.J., Liu Y.H., Wang J.F., Zhou X.J. Antitubercular and cytotoxic tigliane-type diterpenoids from Croton tiglium. Bioorg. Med. Chem. Lett. 2016;26:4996–4999. 10.1016/j.bmcl.2016.09.002. [Abstract] [CrossRef] [Google Scholar]

52. Du Q., Zhao Y., Liu H., Tang C., Zhang M., Ke C., Ye Y. Isolation and structure characterization of cytotoxic phorbol esters from the seeds of Croton tiglium. Planta Med. 2017;83:1361–1367. 10.1055/s-0043-110227. [Abstract] [CrossRef] [Google Scholar]

53. Suirez A.I., Chavez K., Monache F.D., Vasquez L., Delannoy D.M., Orsini G., Compagnone R.S. New 3,4-seco ent-kaurenes from Croton caracasana flowers. Nat. Prod. Commun. 2008;3:319–322. [Google Scholar]

54. Mora S., Castro V., Poveda L., Chavarría M., Murillo R. Two new 3,4-seco-ent-kaurenes and other constituents from the costa rican endemic species Croton megistocarpus. Helv. Chim. Acta. 2011;94:1888–1892. 10.1002/hlca.201100127. [CrossRef] [Google Scholar]

55. Suwancharoen S., Chonvanich O., Roengsumran S., Pornpakakul S. Seco-kaurane skeleton diterpenoids from Croton oblongifolius. Chem. Nat. Compd. 2012;48:583–586. 10.1007/s10600-012-0317-y. [CrossRef] [Google Scholar]

56. Chen W., Yang X.D., Zhao J.F., Yang J.H., Zhang H.B., Li Z.Y., Li L. Three new, 1-oxygenated ent-8,9-secokaurane diterpenes from Croton kongensis. Helv. Chim. Acta. 2006;89:537–541. 10.1002/hlca.200690057. [CrossRef] [Google Scholar]

57. Chen W., Yang X.D., Zhao J.F., Zhang H.B., Li L. Two new, 1-oxygenated ent-kaurane-type diterpenes from Croton kongensis. Helv. Chim. Acta. 2007;90:1554–1558. 10.1002/hlca.200790162. [CrossRef] [Google Scholar]

58. Yang X.-D., Chen W., Zhao J.-F., Yang L.-J., Zhang H.-B., Li L. Ent-kaurane diterpenes and phenolic compounds from Croton kongensis (Euphorbiaceae) Biochem. Syst. Ecol. 2009;37:237–240. 10.1016/j.bse.2009.03.007. [CrossRef] [Google Scholar]

59. Shi S.Q., Fan Y.Y., Xu C.H., Ding J., Wang G.W., Yue J.M. Cytotoxic 8,9-seco-ent-kaurane diterpenoids from Croton kongensis. J. Asian Nat. Prod. Res. 2017 10.1080/10286020.2017.1373100. [Abstract] [CrossRef] [Google Scholar]

60. Mateu E., Chavez K., Riina R.S., Compagnone R., Monache F.D., Suárez A.I. New 3,4-seco-ent-kaurene dimers from Croton micans. Nat. Prod. Commun. 2012;7:5–8. [Abstract] [Google Scholar]

61. Thuong P.T., Pham T.H., Le T.V., Dao T.T., Dang T.T., Nguyen Q.T., Oh W.K. Symmetric dimers of ent-kaurane diterpenoids with cytotoxic activity from Croton tonkinensis. Bioorg. Med. Chem. Lett. 2012;22:1122–1124. 10.1016/j.bmcl.2011.11.116. [Abstract] [CrossRef] [Google Scholar]

62. Kuo P.C., Shen Y.C., Yang M.L., Wang S.H., Thang T.D., Dung N.X., Chiang P.-C., Lee K.-H., Lee E.-J., Wu T.-S. Crotonkinins A and B and related diterpenoids from Croton tonkinensis as anti-inflammatory and antitumor agents. J. Nat. Prod. 2007;70:1906–1909. 10.1021/np070383f. [Abstract] [CrossRef] [Google Scholar]

63. Santos H.S., Barros F.W., Albuquerque M.R., Bandeira P.N., Pessoa C., Braz-Filho R., Monte F.J.Q., Leal-Cardoso J.H., Lemos T.L.G. Cytotoxic diterpenoids from croton argyrophylloides. J. Nat. Prod. 2009;72:1884–1887. 10.1021/np900250k. [Abstract] [CrossRef] [Google Scholar]

64. Dao T.T., Lee K.Y., Jeong H.M., Nguyen P.H., Tran T.L., Thuong P.T., Nguyen B.T., Oh W.K. Ent-kaurane diterpenoids from Croton tonkinensis stimulate osteoblast differentiation. J. Nat. Prod. 2011;74:2526–2531. 10.1021/np200667f. [Abstract] [CrossRef] [Google Scholar]

65. Langat M.K., Crouch N.R., Pohjala L., Tammela P., Smith P.J., Mulholland D.A. Ent-kauren-19-oic acid derivatives from the stem bark of Croton pseudopulchellus Pax. Phytochem. Lett. 2012;5:414–418. 10.1016/j.phytol.2012.03.002. [CrossRef] [Google Scholar]

66. Kuo P.C., Yang M.L., Hwang T.L., Lai Y.Y., Li Y.C., Thang T.D., Wu T.S. Anti-inflammatory diterpenoids from Croton tonkinensis. J. Nat. Prod. 2013;76:230–236. 10.1021/np300699f. [Abstract] [CrossRef] [Google Scholar]

67. Sun L., Meng Z., Li Z., Yang B., Wang Z., Ding G., Xiao W. Two new natural products from Croton kongensis Gagnep. Nat. Prod. Res. 2014;28:563–567. 10.1080/14786419.2013.867856. [Abstract] [CrossRef] [Google Scholar]

68. Kawakami S., Toyoda H., Harinantenaina L., Matsunami K., Otsuka H., Shinzato T., Takeda Y., Kawahata M., Yamaguchid K. Eight new diterpenoids and two new nor-diterpenoids from the stems of Croton cascarilloides. Chem. Pharm. Bull. 2013;61:411–418. 10.1248/cpb.c12-01002. [Abstract] [CrossRef] [Google Scholar]

69. Kawakami S., Matsunami K., Otsuka H., Inagaki M., Takeda Y., Kawahata M., Yamaguchic K. Crotocascarins I-K: Crotofolane-type diterpenoids, crotocascarin γ, isocrotofolane glucoside and phenolic glycoside from the leaves of Croton cascarilloides. Chem. Pharm. Bull. 2015;63:1047–1054. 10.1248/cpb.c15-00635. [Abstract] [CrossRef] [Google Scholar]

70. Kawakami S., Inagaki M., Matsunami K., Otsuka H., Kawahata M., Yamaguchi K. Crotofolane-type diterpenoids, crotocascarins L–Q, and a rearranged crotofolane-type diterpenoid, neocrotocascarin, from the Stems of Croton cascarilloides. Chem. Pharm. Bull. 2016;64:1492–1498. 10.1248/cpb.c16-00500. [Abstract] [CrossRef] [Google Scholar]

71. Gao X.H., Xu Y.S., Fan Y.Y., Gan L.S., Zuo J.P., Yue J.M. Cascarinoids A-C, a class of diterpenoid alkaloids with unpredicted conformations from Croton cascarilloides. Org. Lett. 2018;20:228–231. 10.1021/acs.orglett.7b03592. [Abstract] [CrossRef] [Google Scholar]

72. Filho F.A.S., Junior J.N.S., Braz-Filho R., Simone C.A., Silveira E.R., Lima M.A.S. Crotofolane-and casbane-type diterpenes from Croton argyrophyllus. Helv. Chim. Acta. 2013;96:1146–1154. 10.1002/hlca.201200347. [CrossRef] [Google Scholar]

73. Chávez K., Compagnoneb R.S., Riina R., Briceño A., González T., Squitieri E., Landaetab C., Soscúnd H., Suáreza A.I. Crotofolane diterpenoids from Croton caracasanus. Nat. Prod. Commun. 2013;8:1679–1682. [Abstract] [Google Scholar]

74. Maslovskaya L.A., Savchenko A.I., Pierce C.J., Gordon V.A., Reddell P.W., Parsons P.G., Williams C.M. Unprecedented 1,14-seco-crotofolanes from Croton insularis: Oxidative cleavage of crotofolin C by a putative homo-baeyer-villiger rearrangement. Chem. Eur. J. 2014;20:14226–14230. 10.1002/chem.201404250. [Abstract] [CrossRef] [Google Scholar]

75. Aldhaher A., Langat M., Ndunda B., Chirchir D., Midiwo J.O., Njue A., Schwikkard S., Carew M., Mulholland D. Diterpenoids from the roots of Croton dichogamus Pax. Phytochemistry. 2017;144:1–8. 10.1016/j.phytochem.2017.08.014. [Abstract] [CrossRef] [Google Scholar]

76. Yang L., Wu Z.N., Zhang Y.B., Chen N.H., Zhuang L., Li Y.L., Wang G.C. Three new diterpenoids from Croton laui Merr. et Metc. Nat. Prod. Res. 2017;31:1028–1033. 10.1080/14786419.2016.1266350. [Abstract] [CrossRef] [Google Scholar]

77. Bernardino A.C.S.S., Teixeira A.M.R., de Menezes J.E.S.A., Pinto C.C.C., Santos H.S., Freire P.T.C., Coutinho H.D.M., Sena Junior D.M., Bandeira P.N., Braz-Filho R. Spectroscopic and microbiological characterization of labdane diterpene 15,16-epoxy-4-hydroxy-labda-13(16),14-dien-3,12-dione isolated from the stems of Croton jacobinensis. J. Mol. Struct. 2017;1147:335–344. 10.1016/j.molstruc.2017.06.084. [CrossRef] [Google Scholar]

78. Ramos F., Takaishi Y., Kashiwada Y., Osorio C., Duque C., Acuna R., Fujimoto Y. Ent-3,4-seco-labdane and ent-labdane diterpenoids from Croton stipuliformis (Euphorbiaceae) Phytochemistry. 2008;69:2406–2410. 10.1016/j.phytochem.2008.05.025. [Abstract] [CrossRef] [Google Scholar]

79. Huang H.-L., Qi F.-M., Yuan J.-C., Zhao C.-G., Yang J.-W., Fang F.-H., Wu Q.-X., Gao K., Yuan C.-S. Labdane-type diterpenoids from Croton laevigatus. RSC Adv. 2014;4:39530–39540. 10.1039/C4RA04863F. [CrossRef] [Google Scholar]

80. Pompimon W., Udomputtimekakul P., Apisantiyakom S., Baison W., Penlap N., Chaibun S., Nuntasaen N. Two new labdane-type diterpenoids cinnamate from Croton decalvatus Esser. Nat. Prod. Res. 2017 10.1080/14786419.2017.1408089. [Abstract] [CrossRef] [Google Scholar]

81. Zhang Z.X., Wu P.Q., Li H.H., Qi F.M., Fei D.Q., Hu Q.L., Liu Y.H., Huang X.L. Norcrassin A, a novel C16 tetranorditerpenoid, and bicrotonol A, an unusual dimeric labdane-type diterpenoid, from the roots of Croton crassifolius. Org. Biomol. Chem. 2018;16:1745–1750. 10.1039/C7OB02991H. [Abstract] [CrossRef] [Google Scholar]

82. Yang L., Zhang Y.B., Chen L.F., Chen N.H., Wu Z.N., Jiang S.Q., Jiang L., Li G.Q., Li Y.L., Wang G.C. New labdane diterpenoids from Croton laui and their anti-inflammatory activities. Bioorg. Med. Chem. Lett. 2016;26:4687–4691. 10.1016/j.bmcl.2016.08.052. [Abstract] [CrossRef] [Google Scholar]

83. Pudhom K., Vilaivan T., Ngamrojanavanich N., Dechangvipart S., Sommit D., Petsom A., Roengsumran S. Furanocembranoids from the stem bark of Croton oblongifolius. J. Nat. Prod. 2007;70:659–661. 10.1021/np060520t. [Abstract] [CrossRef] [Google Scholar]

84. Zou G.A., Gang D., Su Z.-H., Yang J.-S., Zhang H.-W., Peng C.-Z., Aisa H.A., Zou Z.-M. Lactonecembranoids from Croton laewigatus. J. Nat. Prod. 2010;73:792–795. 10.1021/np100044t. [Abstract] [CrossRef] [Google Scholar]

85. Mulholland D.A., Langat M.K., Crouch N.R., Coley H.M., Mutambi E.M., Nuzillard J.M. Cembranolides from the stem bark of the southern african medicinal plant, Croton gratissimus (Euphorbiaceae) Phytochemistry. 2010;71:1381–1386. 10.1016/j.phytochem.2010.05.014. [Abstract] [CrossRef] [Google Scholar]

86. Langat M.K., Crouch N.R., Smith P.J., Mulholland D.A. Cembranolides from the leaves of Croton gratissimus. J. Nat. Prod. 2011;74:2349–2355. 10.1021/np2002012. [Abstract] [CrossRef] [Google Scholar]

87. Kawakami S., Matsunami K., Otsuka H., Lhieochaiphant D., Lhieochaiphant S. Two new cembranoids from the leaves of Croton longissimus Airy Shaw. J. Nat. Med. 2013;67:410–414. 10.1007/s11418-012-0693-4. [Abstract] [CrossRef] [Google Scholar]

88. Song J.T., Han Y., Wang X.L., Shen T., Lou H.X., Wang X.N. Diterpenoids from the twigs and leaves of Croton caudatus var. tomentosus. Fitoterapia. 2015;107:54–59. 10.1016/j.fitote.2015.10.006. [Abstract] [CrossRef] [Google Scholar]

89. Song J.-T., Liu X.-Y., Li A.-L., Wang X.-L., Shen T., Ren D.-M., Lou H.-X., Wang X.-N. Cytotoxic abietane-type diterpenoids from twigs and leaves of Croton laevigatus. Phytochem. Lett. 2017;22:241–246. 10.1016/j.phytol.2017.10.007. [CrossRef] [Google Scholar]

90. Santos H.S., Mesquita F.M.R., Lemos T.L.G., Monte F.J.Q., Braz-Filho R. Diterpenos casbanos e acetofenonas de Croton nepetaefolius (Euphorbiaceae) Quim. Nova. 2008;31:601–604. 10.1590/S0100-40422008000300026. [CrossRef] [Google Scholar]

91. e Silva-Filho F.A., Braz-Filho R., Silveira E.R., Lima M.A. Structure elucidation of casbane diterpenes from Croton argyrophyllus. Magn. Reson. Chem. 2011;49:370–373. 10.1002/mrc.2752. [Abstract] [CrossRef] [Google Scholar]

92. Maslovskaya L.A., Savchenko A.I., Krenske E.H., Gordon V.A., Reddell P.W., Pierce C.J., Parsons P.G., Williams C.M. Croton insularis introduces the seco-casbane class with EBC-329 and the first casbane endoperoxide EBC-324. Chem. Commun. 2014;50:12315–12317. 10.1039/C4CC05413J. [Abstract] [CrossRef] [Google Scholar]

93. Roengsumran S., Pata P., Ruengraweewat N., Tummatorn J., Pornpakakul S., Sangvanich P., Puthong S., Petsom A. New cleistanthane diterpenoids and 3,4-seco-cleistanthane diterpenoids from croton oblongifolius. Chem. Nat. Compd. 2009;45:641–646. 10.1007/s10600-009-9442-7. [CrossRef] [Google Scholar]

94. Torres M.C.M., Braz-Filho R., Silveira E.R., Diniz J.C., Viana F.A., Pessoa O.D.L. Terpenoids from Croton regelianus. Helv. Chim. Acta. 2010;93:375–381. 10.1002/hlca.200900201. [CrossRef] [Google Scholar]

95. Zhang Z.-X., Li H.-H., Qi F.-M., Xiong H.-Y., Dong L.-L., Fan G.-X., Fei D.-Q. A new halimane diterpenoid from Croton crassifolius. Bull. Korean Chem. Soc. 2014;35:1556–1558. 10.5012/bkcs.2014.35.5.1556. [CrossRef] [Google Scholar]

96. Maslovskaya L.A., Savchenko A.I., Gordon V.A., Reddell P.W., Pierce C.J., Parsons P.G., Williams C.M. Isolation and confirmation of the proposed cleistanthol biogentic link from Croton insularis. Org. Lett. 2011;13:1032–1035. 10.1021/ol103083m. [Abstract] [CrossRef] [Google Scholar]

97. Maslovskaya L.A., Savchenko A.I., Gordon V.A., Reddell P.W., Pierce C.J., Parsons P.G., Williams C.M. EBC-316, 325–327, and 345: New pimarane diterpenes from Croton insularis found in the Australian rainforest. Aust. J. Chem. 2015;68:652–659. 10.1071/CH14550. [CrossRef] [Google Scholar]

98. Thuong P.T., Dao T.T., Pham T.H., Nguyen P.H., Le T.V., Lee K.Y., Oh W.-K. Crotonkinensins A and B, diterpenoids from the Vietnamese medicinal plant Croton tonkinensis. J. Nat. Prod. 2009;72:2040–2042. 10.1021/np900215r. [Abstract] [CrossRef] [Google Scholar]

99. Rakotonandrasana O.L., Raharinjato F.H., Rajaonarivelo M., Dumontet V., Martin M.-T., Bignon J., Rasoanaivo P. Cytotoxic 3,4-seco-atisane diterpenoids from Croton barorum and Croton goudotii. J. Nat. Prod. 2010;73:1730–1733. 10.1021/np1005086. [Abstract] [CrossRef] [Google Scholar]

100. Adelekan A.M., Prozesky E.A., Hussein A.A., Urena L.D., Rooyen P.H., Liles D.C., Meyer J.J.M., Rodrfguez B. Bioactive diterpenes and other constituents of Croton steenkampianus. J. Nat. Prod. 2008;71:1919–1922. 10.1021/np800333r. [Abstract] [CrossRef] [Google Scholar]

101. Barreto M.B., Gomes C.L., Freitas J.V.B.D., Pinto F.D.C.L., Silveira E.R., Gramosa N.V., Torres D.S.C. Flavonoides e terpenoides de Croton muscicarpa (euphorbiaceae) Quim. Nova. 2013;36:675–679. 10.1590/S0100-40422013000500011. [CrossRef] [Google Scholar]

102. Lopes E.L., Neto M.A., Silveira E.R., Pessoa O.D.L., Braz-Filho R. Flavonoides e sesquiterpenos de Croton pedicellatus kunth. Quim. Nova. 2012;35:2169–2172. 10.1590/S0100-40422012001100012. [CrossRef] [Google Scholar]

103. Zhang Z.-X., Li H.-H., Qi F.-M., Dong L.-L., Hai Y., Fan G.-X., Fei D.-Q. Crocrassins A and B: Two novel sesquiterpenoids with an unprecedented carbon skeleton from Croton crassifolius. RSC Adv. 2014;4:30059–30061. 10.1039/C4RA03798G. [CrossRef] [Google Scholar]

104. Langat M.K., Crouch N.R., Nuzillard J.-M., Mulholland D.A. Pseudopulchellol: A unique sesquiterpene-monoterpene derived C-25 terpenoid from the leaves of Croton pseudopulchellus Pax (Euphorbiaceae) Phytochem. Lett. 2018;23:38–40. 10.1016/j.phytol.2017.11.008. [CrossRef] [Google Scholar]

105. Ghosh P., Mandal A., Rasul M.G. A new bioactive ursane-type triterpenoid from Croton bonplandianum Bail. J. Chem. Sci. 2013;125:359–364. 10.1007/s12039-013-0387-9. [CrossRef] [Google Scholar]

106. Yuan Q.Q., Song W.B., Wang W.Q., Xuan L.J. A new patchoulane-type sesquiterpenoid glycoside from the roots of Croton crassifolius. Nat. Prod. Res. 2017;31:289–293. 10.1080/14786419.2016.1233413. [Abstract] [CrossRef] [Google Scholar]

107. Pan Z.H., Ning D.S., Liu J.L., Pan B., Li D.P. A new triterpenoid saponin from the root of Croton lachnocarpus Benth. Nat. Prod. Res. 2014;28:48–51. 10.1080/14786419.2013.838238. [Abstract] [CrossRef] [Google Scholar]

108. Aderogba M.A., McGaw L.J., Bezabih M., Abegaz B.M. Isolation and characterisation of novel antioxidant constituents of Croton zambesicus leaf extract. Nat. Prod. Res. 2011;25:1224–1233. 10.1080/14786419.2010.532499. [Abstract] [CrossRef] [Google Scholar]

109. Kawakami S., Matsunami K., Otsuka H., Shinzato T., Takeda Y. Crotonionosides A-G: Megastigmane glycosides from leaves of Croton cascarilloides Rauschel. Phytochemistry. 2011;72:147–153. 10.1016/j.phytochem.2010.10.003. [Abstract] [CrossRef] [Google Scholar]

110. Takeshige Y., Kawakami S., Matsunami K., Otsuka H., Lhieochaiphant D., Lhieochaiphant S. Oblongionosides A-F, megastigmane glycosides from the leaves of Croton oblongifolius Roxburgh. Phytochemistry. 2012;80:132–136. 10.1016/j.phytochem.2012.05.011. [Abstract] [CrossRef] [Google Scholar]

111. Mehmood R., Bibi A., Malik A. New secondary metabolites from Croton sparsiflorus Morong. Turk. J. Chem. 2013;37:111–118. [Google Scholar]

112. Mehmood R., Imran M., Safder M., Anjum S., Malik A. Structural determination of crotamides A and B, the new amides from Croton sparsiflorus. J. Asian Nat. Prod. Res. 2010;12:662–665. 10.1080/10286020.2010.489896. [Abstract] [CrossRef] [Google Scholar]

113. Mehmood R., Malik A. New secondary metabolites from Croton sparsiflorus. Z. Naturforsch. B. 2011;66:857–860. 10.1515/znb-2011-0812. [CrossRef] [Google Scholar]

114. Wu X.A., Zhao Y.M., Yu N.J. A novel analgesic pyrazine derivative from the leaves of Croton tiglium L. J. Asian Nat. Prod. Res. 2007;9:437–441. 10.1080/10286020500384781. [Abstract] [CrossRef] [Google Scholar]

115. Barbosa P.S., Abreu A.d.S., Batista E.F., Guilhon G.M.S.P., Müller A.H., Arruda M.S.P., Santos L.S., Arruda A.C., Secco R.S. Glutarimide alkaloids and terpenoids from Croton pullei var. glabrior Lanj. Biochem. Syst. Ecol. 2007;35:887–890. 10.1016/j.bse.2007.04.006. [CrossRef] [Google Scholar]

116. Queiroz M.M.F., Queiroz E.F., Zeraik M.L., Marti G., Favre-Godal Q., Simões-Pires C., Marcourt L., Carrupt P.A., Cuendet M., Paulo M.Q., et al. Antifungals and acetylcholinesterase inhibitors from the stem bark of Croton heliotropiifolius. Phytochem. Lett. 2014;10 10.1016/j.phytol.2014.08.013. [CrossRef] [Google Scholar]

117. Novello C.R., Marques L.C., Pires M.E., Kutschenco A.P., Nakamura C.V., Nocchi S., Sarragiotto M.H., Mello J.C.P. Bioactive indole alkaloids from Croton echioides. J. Braz. Chem. Soc. 2016;27:2203–2209. [Google Scholar]

118. Aderogba M., Ndhlala A.R., Staden J.V. Acetylcholinesterase inhibitors from Croton sylvaticus ethyl acetate leaf extract and their mutagenic effects. Nat. Prod. Commun. 2013;8:795–798. [Google Scholar]

119. Athikomkulchai S., Prawat H., Thasana N., Ruangrungsi N., Ruchirawat S. Cox-1, Cox-2 inhibitors and antifungal agents from Croton hutchinsonianus. Chem. Pharm. Bull. 2006;54:262–264. 10.1248/cpb.54.262. [Abstract] [CrossRef] [Google Scholar]

120. Li H.-H., Qi F.-M., Dong L.-L., Fan G.-X., Che J.-M., Guo D.-D., Zhang Z.-X., Fei D.-Q. Cytotoxic and antibacterial pyran-2-one derivatives from Croton crassifolius. Phytochem. Lett. 2014;10:304–308. 10.1016/j.phytol.2014.10.022. [CrossRef] [Google Scholar]

121. Huang W., Wang J., Liang Y., Li Y., Wang G. Pyran-2-one derivatives from the roots of Croton crassifolius. Nat. Prod. Commun. 2016;11:803–804. [Abstract] [Google Scholar]

122. Quintyne-Walcott S., Maxwell A.R., Reynolds W.F. Crotogossamide, a cyclic nonapeptide from the latex of Croton gossypifolius. J. Nat. Prod. 2007;70:1374–1376. 10.1021/np078007i. [Abstract] [CrossRef] [Google Scholar]

123. Candido-Bacani Pde M., Figueiredo Pde O., Matos Mde F., Garcez F.R., Garcez W.S. Cytotoxic orbitide from the latex of Croton urucurana. J. Nat. Prod. 2015;78:2754–2760. 10.1021/acs.jnatprod.5b00724. [Abstract] [CrossRef] [Google Scholar]

124. Bracher F., Randau K.P., Lerche H. Crototropone, a new tropone derivative from Croton zehntneri. Fitoterapia. 2008;79:236–237. 10.1016/j.fitote.2007.12.001. [Abstract] [CrossRef] [Google Scholar]

125. Randau K.P., Sproll S., Lerche H., Bracher F. Pernambucone, a new tropone derivative from Croton argyroglossum. Pharmazie. 2009;64:350–351. [Abstract] [Google Scholar]

126. Nihei K., Asaka Y., Mine Y., Yamada Y., Iigo M., Yanagisawa T. Musidunin and musiduol, insect antifeedants from Croton jatrophoides. J. Nat. Prod. 2006;69:975–977. 10.1021/np060068d. [Abstract] [CrossRef] [Google Scholar]

127. Zou G.A., Su Z.H., Zhang H.W., Wang Y., Yang J.S., Zou Z.M. Flavonoids from the stems of Croton caudatus Geisel. var. tomentosus Hook. Molecules. 2010;15:1097–1102. 10.3390/molecules15031097. [Europe PMC free article] [Abstract] [CrossRef] [Google Scholar]

128. Ahmat N., Said I.M., Latip J., Din L.B., Syah Y.M., Hakim E.H. New prenylated dihydrostilbenes from Croton laevifolius. Nat. Prod. Commun. 2007;2:1137–1140. [Google Scholar]

129. Attioua B., Weniger B., Chabert P. Antiplasmodial activity of constituents isolated from Croton lobatus. Pharm. Biol. 2007;45:263–266. 10.1080/13880200701214607. [CrossRef] [Google Scholar]

Articles from Molecules are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

Full text links

Read article at publisher's site: https://doi.org/10.3390/molecules23092333

Read article for free, from open access legal sources, via Unpaywall: https://www.mdpi.com/1420-3049/23/9/2333/pdf?version=1536758366

Citations & impact

Impact metrics

Citations

Jump to Citations

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/143130983

Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/143130983

Article citations

Phytochemical Properties of Croton gratissimus Burch (Lavender Croton) Herbal Tea and Its Protective Effect against Iron-Induced Oxidative Hepatic Injury.
Ncume PV, Salau VF, Mtshali S, Olofinsan KA, Erukainure OL, Matsabisa MG
Plants (Basel), 12(16):2915, 10 Aug 2023
Cited by: 0 articles | PMID: 37631127 | PMCID: PMC10459045
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Diabetes-Related Mechanisms of Action Involved in the Therapeutic Effect of Croton Species: A Systematic Review.
Espinoza-Hernández FA, Moreno-Vargas AD, Andrade-Cetto A
Plants (Basel), 12(10):2014, 18 May 2023
Cited by: 0 articles | PMID: 37653931 | PMCID: PMC10223760
Review
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Crotofolane Diterpenoids and Other Constituents Isolated from Croton kilwae.
Mahambo ET, Uwamariya C, Miah M, Clementino LDC, Alvarez LCS, Di Santo Meztler GP, Trybala E, Said J, Wieske LHE, Ward JS, Rissanen K, Munissi JJE, Costa FTM, Sunnerhagen P, Bergström T, Nyandoro SS, Erdelyi M
J Nat Prod, 86(2):380-389, 07 Feb 2023
Cited by: 1 article | PMID: 36749598 | PMCID: PMC9972476
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Impact of Shodhana an Ayurvedic purification process on cytotoxicity and mutagenicity of Croton tiglium Linn.
Jamadagni P, Ranade A, Bharsakale S, Chougule S, Jamadagni S, Pawar S, Prasad GP, Gaidhani S, Gurav A
J Ayurveda Integr Med, 14(2):100710, 01 Mar 2023
Cited by: 0 articles | PMID: 37230917 | PMCID: PMC10307826
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC
Phytochemical Screening and Isolation of New Ent-Clerodane Diterpenoids from Croton guatemalensis Lotsy.
Escandón-Rivera SM, Andrade-Cetto A, Rosas-Ramírez DG, Arreguín-Espinosa R
Plants (Basel), 11(22):3159, 18 Nov 2022
Cited by: 1 article | PMID: 36432893 | PMCID: PMC9692395
This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
Free full text in Europe PMC

Go to all (19) article citations

Funding

Funders who supported this work.

National Natural Science Foundation of China (1)

Grant ID: 21362035
4 publications

Search life-sciences literature (44,031,988 articles, preprints and more)

Chemical Constituents from Croton Species and Their Biological Activities.

Author information

Affiliations

Authors

ORCIDs linked to this article

Abstract

Free full text

Chemical Constituents from Croton Species and Their Biological Activities

Abstract

1. Introduction

2. Chemical Constituents

Table 1

Table 2

Table 3

Table 4

Table 5

Table 6

Table 7

Table 8

Table 9

Table 10

Table 11

Table 12

Table 13

Table 14

Table 15

Table 16

Table 17

Table 18

Table 19

Table 20

Table 21

Table 22

Table 23

Table 24

Table 25

Table 26

Table 27

2.1. Diterpenoids

2.1.1. Clerodanes

2.1.2. Tiglianes

2.1.3. Kauranes

2.1.4. Crotofolanes

2.1.5. Labdanes

2.1.6. Cembranes

2.1.7. Abietanes

2.1.8. Casbanes

2.1.9. Halimanes

2.1.10. Pimaranes

2.1.11. Cleistanthanes

2.1.12. Grayananes, Atisanes, Phytanes, Laevinanes and Meroditerpenoids

2.2. Sesquiterpenoids, Sesterterpenoids and Triterpenoids

2.3. Glycosides

2.4. Alkaloids

2.5. Benzoate Derivatives, Pyran-2-One Derivatives, Cyclicpeptides, Tropone Derivatives and Limonoids

2.6. Miscellaneous Compounds

3. Biological Activities

3.1. Cytotoxic Activity

Table 28

3.2. Anti-Inflammatory Activity

3.3. Antifungal Activity

3.4. Acetylcholinesterase Inhibitory Activity

3.5. Neurite Outgrowth-Promoting Activity

3.6. Other Activities

4. Conclusions

Author Contributions

Funding

Conflicts of Interest

Footnotes

References

Full text links

Citations & impact

Impact metrics

Citations of article over time

Alternative metrics

Article citations

Similar Articles

Funding

National Natural Science Foundation of China (1)﻿

National Natural Science Foundation of China (1)