Abstract

BackgroundSteroid compounds with a 6,19-oxirane bridge possess interesting biological activities including anticonvulsant and analgesic properties, bacteriostatic activity against Gram-positive bacteria and selective anti-glucocorticoid action, while lacking mineralocorticoid and progestagen activity.ResultsThe study aimed to obtain new derivatives of 3β-acetyloxy-5α-chloro-6,19-oxidoandrostan-17-one by microbial transformation. Twelve filamentous fungal strains were used as catalysts, including entomopathogenic strains with specific activity in the transformation of steroid compounds. All selected strains were characterised by high biotransformation capacity for steroid compounds. However, high substrate conversions were obtained in the cultures of 8 strains: Beauveria bassiana KCh BBT, Beauveria caledonica KCh J3.4, Penicillium commune KCh W7, Penicillium chrysogenum KCh S4, Mucor hiemalis KCh W2, Fusarium acuminatum KCh S1, Trichoderma atroviride KCh TRW and Isaria farinosa KCh KW1.1. Based on gas chromatography (GC) and nuclear magnetic resonance (NMR) analyses, it was found that almost all strains hydrolysed the ester bond of the acetyl group. The strain M. hiemalis KCh W2 reduced the carbonyl group additionally. From the P. commune KCh W7 and P. chrysogenum KCh S4 strain cultures a product of D-ring Baeyer–Villiger oxidation was isolated, whereas from the culture of B. bassiana KCh BBT a product of hydroxylation at the 11α position and oxidation of the D ring was obtained. Three 11α-hydroxy derivatives were obtained in the culture of I. farinosa KCh KW1.1: 3β,11α-dihydroxy-5α-chloro-6,19-oxidoandrostan-17-one, 3β,11α,19-trihydroxy-5α-chloro-6,19-oxidoandrostan-17-one and 3β,11α-dihydroxy-5α-chloro-6,19-oxidoandrostan-17,19-dione. They are a result of consecutive reactions of hydrolysis of the acetyl group at C-3, 11α- hydroxylation, then hydroxylation at C-19 and its further oxidation to lactone.ConclusionsAs a result of the biotransformations, seven steroid derivatives, not previously described in the literature, were obtained: 3β-hydroxy-5α-chloro-6,19-oxidoandrostan-17-one, 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane, 3β-hydroxy-5α-chloro-17α-oxa-D-homo-6,19-oxidoandrostan-17-one, 3β,11α-dihydroxy-5α-chloro-17α-oxa-D-homo-6,19-oxidoandrostan-17-one and the three above–mentioned 11α-hydroxy derivatives. This study will allow a better understanding and characterisation of the catalytic abilities of individual microorganisms, which is crucial for more accurate planning of experiments and achieving more predictable results.

Highlights

  • Steroid compounds with a 6,19-oxirane bridge possess interesting biological activities including anticonvulsant and analgesic properties, bacteriostatic activity against Gram-positive bacteria and selective anti-glu‐ cocorticoid action, while lacking mineralocorticoid and progestagen activity

  • Biotransformations are a good alternative to chemical synthesis in obtaining steroid derivatives, with regio- and stereoselectively introduced substituents in nonactivated positions [5, 6]

  • This study will allow a better understanding and characterisation of the catalytic abilities of individual microorganisms, which is crucial for more accurate planning of experiments and achieving more predictable results

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Summary

Introduction

Steroid compounds with a 6,19-oxirane bridge possess interesting biological activities including anticonvulsant and analgesic properties, bacteriostatic activity against Gram-positive bacteria and selective anti-glu‐ cocorticoid action, while lacking mineralocorticoid and progestagen activity. Biotransformations are a good alternative to chemical synthesis in obtaining steroid derivatives, with regio- and stereoselectively introduced substituents in nonactivated positions [5, 6]. The 6,19-oxirane bridge in the structure of steroid compounds causes the skeleton to flex between the A and B rings [9]. There are reports of preventing ventricular fibrillation of 6,19-oxido androstanes [13]. They have analgesic properties and are bacteriostatic against Gram-positive bacteria [13]. Steroid compounds having a 6,19-oxirane bridge are precursors of the contraceptive 19-norsteroids [14]

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