Microbial transformation of 3-hydroxy-5,6-cyclopropanocholestanes--an alternative route to 6-methylsteroids.
Incubation of 3beta-hydroxy-5,6alpha-cyclopropano-5alpha-cholestane (4), 3beta-hydroxy-5,6beta-cyclopropano-5beta-cholestane (5), and 3beta-hydroxy-5,6alpha-cyclopropano-5alpha-cholest-7-e ne (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, 6alpha,7alpha-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, 6alpha-cyclopropano-5alpha-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, 6beta-cyclopropano-5beta-androsta-3,17-dione (10) and 5, 6alpha-cyclopropano-5alpha-androsta-3,17-dione (7), gave 6beta- and 6alpha-methylandrost-4-ene-3,17-dione in 60, and 45% yields, respectively.
Yan
J L
JL
School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Taipei 100, Republic of, Taiwan, China.
Lee
S S
SS
Wang
K C
KC
D000735:Androstenedione / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D001711:Biotransformation; D004083:Cholestanol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009161:Mycobacterium / Q000378:metabolism*; D014961:X-Ray Diffraction
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D000735:Androstenedione; D004083:Cholestanol; D001141:Aromatase