Steroselective synthesis of some steroidal oxazolines, as novel potential inhibitors of 17α-hydroxylase-C17,20-lyase

17β-Oxazolinyl steroids 7a-g and 8a-g were synthesized. The Lewis acid-catalysed reactions of (20R)-3β-acetoxy-21-azidomethyl-20-hydroxypregn-5-ene with substituted aromatic aldehydes led to the formation of 3β-acetoxyandrost-5-enes substituted in position 17β with oxazolinyl residues (7a-g). Oppenauer oxidation of the 3β-hydroxy-exo-heterocyclic steroids yielded the corresponding Δ4-3-ketosteroids. The inhibitory effects (IC50) of both 3-hydroxy compounds 7a-g and their Δ4-3-keto counterparts 8a-g on rat testicular C17,20-lyase were investigated with an in vitro radioligand incubation technique. The 3-chlorophenyl- (8d), and the 4-bromophenyl-17β-(2-oxazolin-5-yl)androst-4-en-3-one derivatives (8f) were found to be modest inhibitors (IC50 = 4.8 and 5.0 μM, respectively).