Microbial transformation of 3-hydroxy-5,6-cyclopropanocholestanes - An alternative route to 6-methylsteroids

• Published in: Steroids 2000-12, Vol.65 (12), p.863-870
• Main Authors: Yan, Jiann-Long, Lee, Shoei-Sheng, Wang, K.C.
• Format: Article
• Language: English
• Subjects: 5,6-Cyclopropanoandrosta-3,17-diones; 5,6-Cyclopropanocholestanes; 6-Methylandrost-4-ene-3,17-diones; Alicyclic compounds, terpenoids, prostaglandins, steroids; Androstenedione - analogs & derivatives; Androstenedione - chemical synthesis; Androstenedione - metabolism; Aromatase - metabolism; Aromatase Inhibitors; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Biotransformation; Chemistry; Cholestanol - analogs & derivatives; Cholestanol - chemical synthesis; Cholestanol - metabolism; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Magnetic Resonance Spectroscopy; Methods. Procedures. Technologies; Microbial transformation; Molecular Structure; Mycobacterium - metabolism; Mycobacterium sp. (NRRL B-3805); Organic chemistry; Preparations and properties; Steroids; X-Ray Diffraction
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/S0039-128X(00)00170-7

Incubation of 3β-hydroxy-5,6α-cyclopropano-5α-cholestane ( 4), 3β-hydroxy-5,6β-cyclopropano-5β-cholestane ( 5), and 3β-hydroxy-5,6α-cyclopropano-5α-cholest-7-ene ( 6) with Mycobacterium sp. (NRRL B-3805) gave a mixture of side chain cleaved 17-keto steroids as the major products in 52, 57, and 69% yields, respectively. Among these 17-keto steroids, the cyclopropyl ring eliminated product, androst-4-ene-3,17-dione ( 9), was isolated in 6, 4, and 8% yields, respectively. A cyclopropyl ring migration product, 6α,7α-cyclopropanoandrost-4-ene-3,17-dione ( 16), was isolated from the incubation mixture of 6 in 4% yield, also 10% yield of 16 was obtained when 5,6α-cyclopropano-5α-androst-7-ene-3,17-dione ( 12) was incubated. The cyclopropyl ring opening and subsequent reduction followed by oxidation of the two major biotransformation products, 5,6β-cyclopropano-5β-androsta-3,17-dione ( 10) and 5,6α-cyclopropano-5α-androsta-3,17-dione ( 7), gave 6β- and 6α-methylandrost-4-ene-3,17-dione in 60, and 45% yields, respectively.