7801-12-9Relevant articles and documents
Microbial Baeyer-Villiger oxidation of 5α-steroids using Beauveria bassiana. A stereochemical requirement for the 11α-hydroxylation and the lactonization pathway
?wizdor, Alina,Panek, Anna,Milecka-Tronina, Natalia
, p. 44 - 52 (2014/03/21)
Beauveria bassiana KCH 1065, as was recently demonstrated, is unusual amongst fungal biocatalysts in that it converts C19 3-oxo-4-ene and 3β-hydroxy-5-ene as well as 3β-hydroxy-5α-saturated steroids to 11α-hydroxy ring-D lactones. The Baeyer-Villiger monooxygenase (BVMO) of this strain is distinguished from other enzymes catalyzing BVO of steroidal ketones by the fact that it oxidizes solely substrates with 11α-hydroxyl group. The current study using a series of 5α-saturated steroids (androsterone, 3α-androstanediol and androstanedione) has highlighted that a small change of the steroid structure can result in significant differences of the metabolic fate. It was found that the 3α-stereochemistry of hydroxyl group restricted "normal" binding orientation of the substrate within 11α-hydroxylase and, as a result, androsterone and 3α-androstanediol were converted into a mixture of 7β-, 11α- and 7α-hydroxy derivatives. Hydroxylation of androstanedione occurred only at the 11α-position, indicating that the 3-oxo group limits the alternative binding orientation of the substrate within the hydroxylase. Only androstanedione and 3α-androstanediol were metabolized to hydroxylactones. The study uniquely demonstrated preference for oxidation of equatorial (11α-, 7β-) hydroxyketones by BVMO from B. bassiana. The time course experiments suggested that the activity of 17β-HSD is a factor determining the amount of produced ring-D lactones. The obtained 11α-hydroxylactones underwent further transformations (oxy-red reactions) at C-3. During conversion of androstanedione, a minor dehydrogenation pathway was observed with generation of 11α,17β-dihydroxy-5α-androst-1-en-3-one. The introduction of C1C2 double bond has been recorded in B. bassiana for the first time.
Microbiological Hydroxylation. Part 23. Hydroxylations of Fluoro-5α-androstanones by the Fungi Calonectria decora, Rhizopus nigricans, and Aspergillus ochraceus
Bird, T. Geoffrey C.,Fredericks, Peter M.,Jones, Ewart R. H.,Meakins, G. Denis
, p. 750 - 755 (2007/10/02)
A series of monofluoro- and gem-difluoro-5α-androstanones and the parent ketones were incubated, under standard conditions, with the fungi named in the title.The results may be rationalised by comparing the positions of the fluorine atoms in the substrates with those of the favoured hydroxylation sites in the parent ketones.With few exceptions hydroxylation does not occur at, or adjacent to, the carbon to which a fluorine substituent is attached even though one of these centres is a favoured site (in the parent ketone).In such cases hydroxylation is usually diverted to an alternative position.Where the favoured site is more distant from the fluorine substituent(s) the behaviour of a fluoro-ketone resembles that of its parent.Hydroxylation of several fluoro-ketones by Aspergillus ochraceus gives the 11α-hydroxy-derivatives cleanly and in yields which are satisfactory for preparative work.
