Elsevier

Phytochemistry

Volume 49, Issue 8, 20 December 1998, Pages 2349-2353
Phytochemistry

The hydroxylation of steroidal ring D lactones by Cephalosporium aphidicola

https://doi.org/10.1016/S0031-9422(98)00286-6Get rights and content

Abstract

The microbiological hydroxylation of 17a-oxa-d-homo-5α-androstane-3,17-dione, the 3β-alcohol and the 13α-methyl analogue by Cephalosporium aphidicola takes place predominantly at C-7α in contrast to other hydroxylations by this organism.

Introduction

The microbiological hydroxylation and eventual cleavage of ring D of the steroids to form a δ-lactone (12) has often been observed1, 2, 3. However, there are relatively few reports of the further transformation of these lactones.

Testolactone (2) has been shown to be hydroxylated at C-2β by a Penicillium sp.[4]and at C-7α by a Dematiaceae sp.[5]. The microbiological hydroxylation of steroids has been rationalized in terms of a triangular relationship with defined dimensions between two binding sites and the site of hydroxylation6, 7. Typically, the steroids have oxygen functions at C-3 and at C-17. The conversion of ring D to a δ-lactone alters the structure of one of the binding groups. In the light of our interest8, 9in the microbiological hydroxylation of steroids by Cephalosporium aphidicola, we have examined the effect of this change on the pattern of hydroxylation by this organism. This fungus is capable of hydroxylating progesterone, firstly at C-11α and then at C-6β, whilst testosterone is hydroxylated at the C-6β position with hydroxylation, to a minor extent, occurring at the C-11α and C-14α positions.

Section snippets

Results and discussion

The lactones were prepared in both the 13α-methyl series and in the natural 13β-methyl series in order to assess the effect of the stereochemistry of ring D. The substrates, 17a-oxa-d-homo-5α.13α-androstane-3,17-dione (3), 17a-oxa-d-homo-5α-androstane-3,17-dione (7) and the corresponding 3β-alcohol (9) were obtained via a Baeyer–Villiger oxidation of the relevant 3β-acetoxy-17-ketone followed by hydrolysis with methanolic K2CO3 and oxidation with CrO3.

The substrates were incubated with

Experimental

General experimental and fermentation conditions have been described previously[11].

References (13)

  • A Farooq et al.

    Phytochemistry

    (1994)
  • J.R Hanson et al.

    Phytochemistry

    (1996)
  • J.R Hanson et al.

    Phytochemistry

    (1993)
  • H Levy et al.

    Journal of Biological Chemistry

    (1947)
  • J Fried et al.

    Journal of the American Chemical Society

    (1953)
  • D.H Peterson et al.

    Journal of the American Chemical Society

    (1953)
There are more references available in the full text version of this article.

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