The hydroxylation of steroidal ring D lactones by Cephalosporium aphidicola
Introduction
The microbiological hydroxylation and eventual cleavage of ring D of the steroids to form a δ-lactone (1→2) 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)
- et al.
Phytochemistry
(1994) - et al.
Phytochemistry
(1996) - et al.
Phytochemistry
(1993) - et al.
Journal of Biological Chemistry
(1947) - et al.
Journal of the American Chemical Society
(1953) - et al.
Journal of the American Chemical Society
(1953)
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2017, Biochimica et Biophysica Acta - Molecular and Cell Biology of LipidsCitation Excerpt :Previous studies on the metabolic fate of these molecules by the filamentous fungus Aspergillus tamarii [13] demonstrated that these structural architectures can be hydroxylated in all four possible binding orientations within the steroid hydroxylase, with monohydroxylation occurring at both axial and equatorial positions. This flexibility of steroidal lactone/hydroxylase binding orientation is facilitated by increased symmetry imparted by having a six-membered ring-D. Structurally this results in the C-17 carbonyl group being transposed in to a more central position in the plane of the steroid [14] nucleus, as compared to steroids with a C-17 keto architecture. The metabolism of the steroidal lactones by Corynespora cassiicola has revealed a unique rearrangement reaction (Fig. 1).
Microbial Baeyer-Villiger oxidation of steroidal ketones using Beauveria bassiana: Presence of an 11α-hydroxyl group essential to generation of D-homo lactones
2011, Biochimica et Biophysica Acta - Molecular and Cell Biology of LipidsCitation Excerpt :In the culture of this strain, 3β-hydroxy-17a-oxa-d-homo-5α-androstan-17-one was converted to a mixture of 1β-, 6β-, 7β-, 11α- and 11β-hydroxy derivatives [14]. Small amounts of 7α- and 9α-hydroxy derivatives were isolated after transformation of this 3β-hydroxy-d-lactone by Cephalosporium aphidicola [15]. 15α-Hydroxytestololactone together with the testololactone was among the products of DHEA transformation by Penicillium griseopurpureum Smith [16].
Biotransformation of dehydroepiandrosterone (DHEA) with Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling
2010, SteroidsCitation Excerpt :So, the compound 9 was proposed to be 3β-hydroxy-17a-oxa-d-homo-5α-androstan-17-one. The NMR data were in accord with those reported in the literature [45]. IR (KBr) νmax (cm−1): 3430, 2933, 2860 and 1701; MS (ESI) m/z [M+H]+ 307.4719; 1H NMR (CDCl3) δ (ppm): 0.78 (3H, s, H-19), 1.30 (3H, s, H-18), 1.13 (1H, m, H-5), 3.60 (1H, m, 3α-H); 13C NMR data, see Table 1.
Transformation of some 3α-substituted steroids by Aspergillus tamarii KITA reveals stereochemical restriction of steroid binding orientation in the minor hydroxylation pathway
2010, Journal of Steroid Biochemistry and Molecular Biology