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First published on 16th January 2007

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Halogenated C₁₅-acetogenins, including the obtusallene family, have been found in red algae of the Laurencia species. D. C. Braddock has proposed a self-consistent biosynthetic pathway to this group involving a sequence of electrophilic bromination events (Org. Lett., 2006, 8, 6055). The hypothesis correctly predicts the stereo- and regiochemistry of obtusallenes whose structures have been confirmed by X-ray analysis, such as obtusalene I 1. However, the structures of other members of the family do not fit the hypothesis, and the author proposes that they may need structural revision, or that the hypothesis needs to be further refined. The proposed structures of elatenyne 2 from Laurencia elata and the enyne 3 from Laurencia majuscula have been synthesised and shown not to be identical with the natural products (J. W. Burton and co-workers, Angew. Chem., Int. Ed., 2006, 45, 7199). The authors propose that the structures should be revised to the 2,2′-bifuranyl derivatives 4 and 5, respectively.

Synthetic studies have demonstrated that the structure of aspergione B 6, a metabolite of Aspergillus versicolor, should be revised to that of pseudodeflectusin 7 from Aspergillus pseudodeflectus (S. Kobayashi and co-workers, Eur. J. Org. Chem., 2006, 4796). The isokibdelones, such as isokibdelone A 8, metabolites of a Kidbelosporangium species, have a new polyketide framework (R. J. Capon, and co-workers, Org. Lett., 2006, 8, 5267). The authors give a plausible biosynthetic pathway to the isokibdelones. Cruentarens A 9 and B 10 are metabolites of the myxobacterium Byssovorax cruenta (G. Höfle and co-workers, Eur. J. Org. Chem., 2006, 5036). The 12-membered lactone ring of cruentaren A 9 is converted into the isomeric cruentaren B 10 under either acidic or basic conditions. The biosynthesis of cruentaren A has been studied using labelled precursors. The sponge-derived fungus Gymnascella dankaliensis is the source of several cytostatic metabolites including gymnastatin G 11, which has an unusual bicyclo[3.3.1]nononane ring system (A. Numata and co-workers, J. Nat. Prod., 2006, 69, 1384). The highly cytotoxic hopeanol 12, from the bark of Hopea exalata, has a new carbon skeleton (R. X. Tan and co-workers, Eur. J. Org. Chem., 2006, 5551). The authors discuss the biogenesis of hopeanol 12.

The reported structure of the sesquiterpenoid dichomitol 13, a metabolite of Dichomitus squalens, has been synthesised and shown to be not identical to the natural product (G. Mehta et al., Tetrahedron Lett., 2006, 47, 8355). The sesquiterpenoid 14, with a novel skeleton, has been identified in the soft coral Clavularia inflat var. luzoniana (C.-Y. Duh and co-workers, J. Nat. Prod., 2006, 69, 1411). The soft coral Paralemnalia thyrsoides is the source of the novel sesquiterpenoids paralemnanone 15, isoparalemnanone 16 and paralemnanol 17 (J.-H. Sheu and co-workers, Tetrahedron Lett., 2006, 47, 8751). Sesquiterpenoids with new skeletal types from the terrestrial environment include incisol 18 from Xenophyllum incisum (C. A. N. Catalán and co-workers, Biochem. Syst. Ecol., 2007, 35, 169) and dayejijiol 19 from Chloranthus henryi (Y. Pan and co-workers, Tetrahedron Lett., 2007, 48, 453). Vibralactone 20, a metabolite of Boreustereum vibrans, is possibly a trinorsesquiterpenoid (J.-K. Liu and co-workers, Org. Lett., 2006, 8, 5749). The essential oil of Santalum album is a rich source of sesquiterpenoids such as β-santalene 21. C. G. Jones et al. have proposed biosynthetic pathways based on the co-occurance of these sesquiterpenoids (Phytochemistry, 2006, 67, 2463). C. I. Keeling and J. Bohlmann have reviewed the biosynthetic pathways to diterpenoids found in the resins of conifers (Phytochemistry, 2006, 67, 2415).

The name ranunculane is proposed for the new triterpenoid skeleton of podocarpaside 22 from Actaea podocarpa (I. A. Khan and co-workers, Org. Lett., 2006, 8, 5529). The 18-nor-14,15-secowithanolide withaphysanolide A 23 has been isolated from Physalis divericata (L. Ma et al., Tetrahedron Lett., 2007, 48, 449). The structure of withaphysanolide A 23 was confirmed by X-ray analysis and the authors propose a biosynthetic pathway. The C₃₅-terpenoids ferrugicadinol 24 and ferrugieudesmol 25 have beeen isolated from the bark of Calocedrus macrolepis var. formosana (Y.-H. Kuo and co-workers, J. Nat. Prod., 2006, 69, 1611). An unusual tetraterpenoid acalyphaser A 26 has been isolated from Acalypha siamensis (H. Kambara et al., Chem. Biodiversity, 2006, 3, 1301).

The first examples of N,C-coupled naphthyldihydroisoquinoline alkaloids, ancistrocladinium A 27 and ancistrocladinium B 28, have been isolated from an Ancistrocladus species (G. Bringmann et al., J. Org. Chem., 2006, 71, 9348). The structure of chaetominine 29, a metabolite of the endophytic fungus Chaetomium sp. IFB-E015, was confirmed by X-ray analysis (R. X. Tan and co-workers, Org. Lett., 2006, 8, 5709). Exiguamine A 30, from the sponge Neopetrosia exigua, also had its structure confirmed by X-ray analysis (R. J. Anderson and co-workers, J. Am. Chem. Soc., 2006, 128, 16046). The authors suggest a biogenesis for this interesting metabolite. The zwitterionic alkaloid daphnicyclidin L 31, with a highly delocalised anion, has been found in the stem bark of Daphniphyllum macropodum (L.-H. Hu, Chem. Biodiversity, 2006, 3, 1255).

P. H. M. Harrison and co-workers have used [¹³C,¹⁸O]-labelled precursors to probe the biosynthesis of the acyltetramic acid, streptolydigin 32 (Org. Lett., 2006, 8, 5329). The results of these feeding studies limit the number of proposed pathways to streptolydigin and confirm the likely mechanism of formation of the polyketide derived ketal. Feeding studies have also been used to investigate the biosynthetic origin of the cyclic imine toxin, 13-desmethylspirolide C 33 (J. A. Walter and co-workers, J. Org. Chem., 2006, 71, 8724). Incorporation of labelled acetate and glycine show that most of the macrocycle carbons are polyketide derived while the glycine is incorporated intact into the cyclic imine moiety. 1,3-Bisphosphoglycerate 34 has identified as the metabolic source of methoxymalonyl-ACP 35, the substrate used to incorporate glycolate units into ansamitocin P-3, soraphen A and other antibiotics (H. G. Floss and co-workers, J. Am. Chem. Soc., 2006, 128, 14325). S. E. O'Connor and co-workers have shown that the biosynthetic machinery of terpene indole alkaloids can accept unnatural substrates resulting in the formation of novel alkaloid structures (J. Am. Chem. Soc., 2006, 128, 14276).

An engineered alanine racemase has been shown to catalyse a retroaldol reaction of α-substituted β-phenylserines (Scheme 1) (D. Hilvert and co-workers, Angew. Chem., Int. Ed., 2006, 45, 6824). Computer modelling suggests that the active site of this mutant enzyme could be further optimised, leading to the practical synthesis of novel amino acids. D. R. Boyd and co-workers have used toluene and biphenyl dioxygenases (TDO and BPDO) to catalyse the enantiopure formation of bis(cis-diol) and cis-diol acetonide metabolites of polyaromatic hydrocarbons (Chem. Commun., 2006, 4934).

Several mutants of cyclohexanone monooxygenase (CHMO) have been studied as catalysts for Baeyer–Villiger oxidation of 4-substituted and 4,4-disubstituted cyclohexanones (M. M. Kayser and C. M. Clouthier, J. Org. Chem., 2006, 71, 8424). For a number of substrates, a mutant with a single exchange, Phe432Ser, was found to be more selective as a catalyst than the wild-type CHMO (Scheme 2). Further work on this transformation has been studied using cyclopentanone monooxygenase (CPMO) (M. M. Kayser and co-workers, J. Org. Chem., 2006, 71, 8431). Selective mutation of CPMO succeeded in identifying mutants which had greatly enhanced enantioselectivity for both nonpolar and polar 4-substituted cyclohexanones. A Baeyer–Villiger monooxygenase (BVMO) from Pseudomonas fluorescens DSM 50106 has been used to carry out the first BVMO-catalysed kinetic resolution of aliphatic acyclic ketones (A. Kirschner and U. T. Bornscheuer, Angew. Chem., Int. Ed., 2006, 45, 7004). Incubation of 4-hydroxy-2-ketones with BVMO gives the with S-configured oxidation product in greater than 90% ee (Scheme 3).

A cytochrome P450 RhF from a Rhodococcus sp. has been shown to catalyse the dealkylation of substituted alkyl aryl ethers (Scheme 4) (S. L. Flitsch and co-workers, Chem Commun., 2006, 4492). Analysis of the substrate specificity of this enzyme revealed that the aromatic ring is important for substrate recognition, and that those substrates with shorter alkyl ethers react faster than those with an extended alkyl chain. H. Luna and co-workers have used crude preparations from mamey (Pouteria sapota), capulin (Prunus serotina var. capulli) and peach (Prunus persica) for the enantioselective addition of HCN to a wide range of aldehydes (Tetrahedron: Asymmetry, 2006, 17, 2813). For example, reaction of benzaldehyde and HCN in the presence of leaves from capulin gave the corresponding cyanohydrin in >99% ee and with 95% conversion (Scheme 5). A novel one-step synthesis of halogenated tryptophans has been reported using a commercially available lysate containing tryptophan synthase (R. J. M. Goss and co-workers, Chem. Commun., 2006, 4924). This PLP-dependent process is highly scalable and gives the tryptophan derivatives in good yields (Scheme 6).

L. Hua and co-workers have examined the substrate specificity of a nitrilase from cyanobacterium Synechocystis sp. strain PCC 6803 (Eur. J. Org. Chem., 2006, 5238). The nitrilase catalyses the hydrolysis of both aromatic and aliphatic nitriles in good yields, and its ability to carry out stereoselective hydrolysis of phenyl-substituted β-hydroxy nitriles was also demonstrated. The kinetic resolution of β-hydroxy selenides using an immobilised lipase in toluene has been reported (M. Gruttadauria and co-workers, Tetrahedron: Asymmetry, 2006, 17, 2713). Acetylation using vinyl acetate gave the corresponding products in excellent enantiomeric excess (Scheme 7).

A novel anthracene-tagged DNA probe that can detect a single base-pair mismatch in a target sequence using fluorescence emission has been developed (D. M. Bassani and co-workers, Chem. Commun., 2006, 5003). M. D. Smith and co-workers have demonstrated that trans-cyclopropane γ-peptides adopt an infinite parallel sheet structure in the solid state (Chem. Commun., 2006, 5006). X-Ray crystallography showed that these structures are stabilised by intermolecular C–H⋯O hydrogen bonds.

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