Microbiological Hydroxylation

Microbiological Hydroxylations.—Microbiological hydroxylations of steroid substrates are too numerous for general inclusion in this report, but two results are of particular interest, d- And d/-19-nortestosterone, incubated with Curvularia lunata, both afforded the d-lO/9-hydroxy-derivative as major product, implying enzyme specificity for the d-form. Several minor products, however, resulted from non-specific attack upon the two antipodes. The 11 - and 6/ -hydroxylated derivatives, for example, were obtained as d/-mixtures from the dZ-steroid. ... 

It was subsequently discovered that lucanthone is metabolized in the body in part to hycanthone (30), a compound with enhanced schistomacidal activity. The relatively high biologic activity of lucanthone in experimental animals compared to man was subsequently attributed to the inefficient hydroxylating system present in man for this biochemical conversion.Microbiologic oxidation of lucanthone by fermentation with the fungus Aspergil-lus scelorotium affords hycanthone. ... 

Archelas A, J-D Fonmeron, R Fnrstoss, M Cesario, C Pascard (1988) Microbial transformations. 8. First example of a highly enantioselective microbiological hydroxylation process J Amer Chem Soc 53 1797-1799. 

Bird TG, PM Fredricks, ERH Jones, GD Meakins (1980) Microbiological hydroxylations. Part 23. Hydroxyl-ations of fluoro-5a-androstanones by the fnngi Calonectria decora, Rhizopus nigricans, and Aspsrgillus ohraceus. J Chem Soc Perkin 1 750-755. 

Microbiological oxidation has proven of enormous value in steroid chemistry, often affording selective means of functionalizing remote and chemically inactivated positions. It will bear mentioning that the 11-oxygen for all commercially available corticoids is in fact introduced by such a reaction carried out on plant scale. Preparation of the 1-dehydro analogue of 207 involves biooxidation to introduce the 16-hydroxyl. Incubation of 6a-fluoroprednisolone... 

Epoxyketone 245 is readily available from 16-dehydropregnenolone via several steps, including a crucial microbiological 11a-hydroxylation. Dehydration of 245 gives the 9,11-olefin 246. The alcohol at C-21 is then converted to the mesylate (247), and this is reduced to give the methyl ketone (248). The olefin is then converted to the 9a-fluoro-llp-hydroxy array (250) by the standard sequence [addition of HOBr, closure to the oxirane (249), opening with HF]. Note that the reactivity of the epoxides in 249 is... 

The microbiological transformation of several yohimbines and derivatives resulted almost exclusively in aromatic-ring hydroxylated compounds (298, 299). 

Takaichi, S., K. Shimada, and J.-I. Ishidsu. 1990. Carotenoids from the aerobic photosynthetic bacterium Erytkrobacter longus P-carotene and its hydroxyl derivatives. Archives of Microbiology 153 118-122. 

Recently the hydroxy metabolites of various sulfonamides could be Isolated and purified, so that specific HPLC techniques could be developed (22,23). As shown in Figure 1, sulfadimidine can be metabolized by hydroxylation at the 5 and 6 position of the pyrimidine ring and by the acetylation- deacetylation pathway (21). After hydroxylation, the metabolites may become glucuronidated and also acetylated (Figure 2). The hydroxy metabolites are microbiologically active and they can be potentiated by trimethoprim (13). 

Levodopa Levodopa, (-)-3-(3,4-dihydroxyphenyl)-L-alanine (10.1.1), is a levorotatory isomer of dioxyphenylalanine used as a precursor of dopamine. There are a few ways of obtaining levodopa using a semisynthetic approach, which consists of the microbiological hydroxylation of L-tyrosine (10.1.1) [1,2], as well as implementing a purely synthetic approach. 

Side reactions of microbiological oxidation using the very same microorganisms can cause hydroxylation of steroids in different positions, using easily accessible progesterone [1-5] as an initial substance [1-5]. 

Fig. 11. Influence of the presence offluorine atoms on microbiological hydroxylation [50,51].

T.G.C. Bird, P.M. Fredericks, E.R.FI. Jones, G.D. Meakins, Microbiological hydroxylation. Part 23. Flydroxylations of fluoro-5ot-androstanones by the fungi Calonectria decora, Rhizopus nigricans, and Aspergillus ochraceus, J. Chem. Soc. Perkin Trans. 1 (1980) 750-755. 

Last year s Report numbered some hydroxylated cannabinoid metabolites inconsistently. The numbering system used in these Reports (see Vol. 2, p. 61) requires that the pentyl side-chain be numbered C-1" — C-5" references to microbiological hydroxylation last year (Vol. 7,pp. 50,51) designated as occurring at C-1, C-2, C-3, C-4, and C-5 referred to side-chain-hydroxylated metabolites which should have been numbered C-T, C-2", C-3", C-4", and C-5" respectively. 

A vast amount of research resulted in the improvement of this bioconversion, as well as the development of many other microbiological reactions. Some of these include Ci-dehydrogenation, C 6-a-hydroxylation, and Cj i-P-hydroxylation of steroids [45-52]. Other... 

Lambert, M., Kremer, S., Sterner, O. Anke, H. (1994). Metabolism of pyrene by the basidiomycete Crinipellis stipitaria and identification of pyrenequinones and their hydroxylated precursors in strain JK375. Applied and Environmental Microbiology, 60, 3597-601. 

Higson, F. K. Focht, D. D. (1989). Bacterial metabolism of hydroxylated biphenyls. Applied and Environmental Microbiology, 55, 946-52. 

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