Nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene: A novel and general route to 17-substituted steroids. Part 1 - synthesis of novel 17-azolyl-Δ16 steroids; inhibitors of 17α-hydroxylase/17, 20-lyase (17α-lyase)

✍ Scribed by Vincent C.O. Njar; Gregory T. Klus; Angela M.H. Brodie

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 283 KB
• Volume: 6
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(96)00512-4

✦ Synopsis

We have discovered that chlorine in 3~-acetoxy-17-chloro-16-formylandrosta-5,16-diene (1) can be smoothly displaced by nitrogen heterocyclic nucleophiles (her) to give heretofore unknown 17-substituted-A t6 steroids in high yields (73-92%). This enabled us to synthesize novel 3~-hydroxy-17-(1H-1,2,4-triazol-1yl)androsta-5,16-diene (4) and 313-hydroxy-17-(1H-imidazol-l-yl)androsta-5,16-diene (7), both of which are potent inhfokors of rat testicular 17a-lyase. Spectroscopic studies with a modified form of human 17a-lyase indicates that the inhibition process involves coordination of steroidal azole nitrogen to the heine-iron of the enzyme.