Synthesis and bioconversions of formestane.
In an effort to generate new steroidal aromatase inhibitors, formestane (4-hydroxyandrost-4-ene-3,17-dione) (1) was biotransformed by Rhizopus oryzae to yield the known 4β,5α-dihydroxyandrostane-3,17-dione as the major product (5) and bioconverted by Beauveria bassiana to afford the known reduced 4,17β-dihydroxyandrost-4-en-3-one (6) and 3α,17β-dihydroxy-5β-androstan-4-one (7) and the new 4,11α,17β-trihydroxyandrost-4-en-3-one (8). All the metabolites showed more potent activities than their parent congener in the aromatase and MCF-7 breast cancer assays. The bioactivities and structural elucidation of these metabolites as well as the semisynthesis of formestane (1) from testosterone (2) are reported herein.
Chemistry, Biochemistry and Physics Department, The University of Tampa , 401 West Kennedy Boulevard, Tampa, Florida 33606-1490, United States.
Glenroy D A
GD
Martin
Javier
J
Narvaez
Anne
A
Marti
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052982:Beauveria / Q000378:metabolism*; D001711:Biotransformation; D001943:Breast Neoplasms; D005260:Female; D006801:Humans; D013237:Stereoisomerism; D013739:Testosterone / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D047072:Aromatase Inhibitors; D013739:Testosterone; D000735:Androstenedione; C014594:formestane