Synthesis of 19-oxygenated 4beta,5beta-epoxy derivatives of 16alpha-hydroxyandrostenedione as mechanistic and catalytic probes for aromatase reaction.
4Beta,5beta-epoxy derivatives of 16alpha-hydroxyandrostenedione (2), one of the natural substrates for aromatase, and its 19-oxygenated compounds 4 and 5 were synthesized as mechanistic and catalytic probes for the enzyme reaction. Treatment of 16alpha-bromoandrostenedione (13) or its 19-hydroxy analog 19 which was prepared from 3beta-hydroxy-19-(tert-butyldimethylsiloxy)androst-5-en-17-one (16) in three steps, with H2O2 and NaOH followed by controlled alkaline hydrolysis with NaOH in aqueous pyridine stereospecifically yielded 4beta,5beta-epoxy-16alpha-ol 15 or 4beta,5beta-epoxy-16alpha,19-diol 22, respectively. Oxidation of 16beta-bromo-4beta,5beta-epoxy-19-ol 21 with pyridinium dichromate followed by controlled alkaline hydrolysis produced 4beta,5beta-epoxy-16alpha-hydroxy-19-al 24.
Numazawa
M
M
Tohoku Pharmaceutical University, Sendai, Japan. numazawa@tohoku-pharm.ac
Yoshimura
A
A
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D002384:Catalysis; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000378:metabolism; D007202:Indicators and Reagents; D013816:Thermodynamics
D047072:Aromatase Inhibitors; D004852:Epoxy Compounds; D007202:Indicators and Reagents; D000735:Androstenedione; C018202:16-hydroxyandrost-4-en-3,17-dione; D001141:Aromatase