Alistair L. Wilkins

Microbiological hydroxylation. Part XIV. Hydroxylation in the terminal rings of dioxygenated 5α-androstanes with the fungi Wojnowicia graminis and Ophiobolus herpotrichus

Dioxo-5α-androstanes having one keto-group in a terminal ring (at position 3 or 2, or at position 17) and the second at a middle ring position (7 or 11) are hydroxylated in the other terminal ring (at 17 or 16, or at 3 or 2) by the fungi Wojnowicia graminis and Ophiobolus herpotrichus. Efficient transformations include the 2α-hydroxylation of 5α-androstane-7,17-dione (with W. graminis), the 16-substitution of the 3,11-dione (with O. herpotrichus), and the 17β-hydroxylation of 3,7-dioxygenated substrates (with both fungi).

Microbiological hydroxylation. Part XVII. C-19 hydroxylation of 17-oxo-5α-androstanes and 17-oxo-3α,5-cyclo-5α-androstanes by the fungus Calonectria decora

The sequence of microbiological reactions involved in the 19-hydroxylation of 5α-androstan-17-one has been established. When a solution of 5α-androstan-17-one in dimethyl sulphoxide is incubated with Calonectria decora, the initial 1β,6α-dihydroxylation is followed by oxidation of the 1β-hydroxy-group and then by hydroxylation at C-19 to give 6α,19-dihydroxy-5α-androstane-1,17-dione in 36% yield. This compound is readily transformed (by chemical methods) into 5α,10β-estrane-1,6,17-trione.C-19 hydroxylation occurs also with certain substituted 17-oxo-5α-androstanes and 17-oxo-3α,5-cyclo-5α-androstanes.

Studies in the steroid group. Part LXXXV. Convenient preparations of 3,6- and 6,17-dioxygenated 5α-androstanes

Convenient, efficient sequences involving 3α,5-cyclo-intermediates have been developed for obtaining 3,6- and 6,17-dioxygenated 5α-androstanes from the cheap steroid 3β-hydroxyandrost-5-en-17-one. Useful selective reactions of 5α-androstane derivatives are achieved by acetalising diketones in the presence of an ion-exchange resin and by oxidising dihydric alcohols with the Fetizon (silver carbonate) reagent.

Microbiological hydroxylation. Part XX. Hydroxylation of dioxygenated 5α-androstanes with the fungi Absidia regnieri and Syncephelastrum racemosum

Dioxygenated androstanes are readily hydroxylated by the title fungi. Although complex mixtures are generally formed, 3β-hydroxy-5α-androstan-7-one is converted efficiently into its 12α-hydroxy-derivative (51% yield) by S. racemosum. The poor steroid recoveries of incubations involving 3,17-dioxygenated substrates and A. regnieri are improved by using a medium containing cobalt(II) sulphate: under such conditions 3β-hydroxy-5α-androstan-17-one gives 3β,9α-dihydroxy-5α-androstan-17-one in 49% yield.

Microbiological hydroxylation. Part XVI. Incubation of derivatives (mainly acetals) of 5α-androstane ketones with the fungi Calonectria decora, Aspergillus ochraceus, and Rhizopus nigricans

Acetals and enol ethers derived from oxoandrostanes are less reactive than the parent ketones towards the title fungi. None of the derivatives is hydroxylated by Rhizopus nigricans, and only one by Aspergillus ochraceus. With Calonectria decora the acetals generally give patterns of hydroxylation similar to, but less specific than, those of the corresponding ketones. 16,16-Ethylenedioxy-5α-androstane is exceptional in that its hydroxylation with Calonectria decora to a 6α,12β-dihydroxy-product is more efficient than the 6α,11α-dihydroxylation of 5α-androstan-16-one.

Lichens and fungi. Part XII. Dehydration and isomerization of stictane triterpenoids

N.m.r. spectral data of a number of stictane derivatives have provided further support for the structure proposed for stictane, and the absence of an 8β-methyl group in this series of compounds has been verified.

Microbiological hydroxylation. Part XXII. Hydroxylation of 3,20-, 7,20-, and 11,20-dioxygenated 5α-pregnanes

Eight 3,20-, 7,20-, and 11,20-dioxygenated 5α-pregnanes have been incubated with the fungi Calonectria decora and Daedalea rufescens, and with three Rhizopus species. In most cases complex mixtures are formed, and the hydroxylations are less satisfactory than those of dioxygenated androstane analogues. Although Rhizopus nigricans leads mainly to the 11α-hydroxylation of 5α-pregnane-3,20-dione, hydroxylation of 3β-hydroxy-5α-pregnan-20-one occurs predominantly at the 7β-position (not at the 11α-position as reported in the literature). The cleanest incubation studied here is that of 5α-pregnane-7,20-dione with Calonectria decora, which gives the 1α,12β-dihydroxy-7,20-dione (30%) and the 12β-hydroxy-1,7,20-trione (19%).Convenient preparations of the 7,20- and 11,20-dioxygenated substrates have been developed.

Lichens and fungi. Part XIII. Comparison of the nuclear magnetic resonance and mass spectra of 17,21-secohopane and 17,21-secoflavicane derivatives

N.m.r. and mass spectral data for derivatives of 17,21-secohopane and 17,21-secoflavicane provide supporting evidence for the structure proposed for flavicane, rings C, D, and E of which are considered to be antipodally related to rings C, D, and E of 21 α-Hhopane.

Microbiological hydroxylation. Part XXI. Hydroxylations of 3-halogeno-17-oxo-, 3-halogeno-7-oxo-, and 17-halogeno-3-oxo-androstanes by the fungi Calonectria decora, Rhizopus nigricans, and Aspergillus ochraceus

The hydroxylations set out in the title have been studied and the results compared with those (obtained in earlier work) of hydroxylating the parent 3-, 7-, and 17-ketones. The microbiological effect of a halogeno-substitutent depends on its nature, position, and configuration in the steroid nucleus. The 3α-fluoro-, 3α-chloro-, and 3α-bromo-5α-androstan-17-ones undergo 1β,6α-dihydroxylation with C.decora; while the 3β-chloro- and 3β-bromo-analogues are more reactive (and are also hydroxylated initially in this way), the 3β-fluoro-17-ketone is recovered essentially unchanged. Loss of halogen generally occurs during incubations of 3-halogeno-17-ketones with R.nigricans, the products being 3-oxo- and 3β-hydroxy-compounds. A.ochraceus converts the fluoro-ketones (but not the chloro-ketones) into their 11α-hydroxy- or 7β,11α-dihydroxy-derivatives; the former process has been utilised in the preparation of 3α- and 3β-fluoro-5α-androstane-11,17-dione.

Lichens and fungi. Part XI. Isolation and structural elucidation of a new group of triterpenes from Sticta coronata, S. colensoi, and S. flavicans

Ten new triterpenes, derived from a new triterpane system for which the name stictane is proposed, have been isolated from the hexane extractives of the lichens named in the title.