Synthesis of 21,21-difluoro-3β-hydroxy-20-methylpregna-5,20-diene and 5,16,20-triene as potential inhibitors of steroid C17(20) lyase

Novel 21,21-difluorovinyl steroids, designed as difluorinated C-20(21) enol mimics of pregnenolone, were targeted as potential mechanism-based inhibitors Of C-17(20) lyase, a crucial enzyme in the biosynthesis of testosterone. Addition of (difluoromethyl)diphenylphosphine oxide reagent to 17-acetyl steroids was the approach chosen for the construction of these compounds. Of particular interest were the abnormal Wittig products which formed during attempted preparation of the triene 9. The target difluoroolefin 3 was found to be a moderately potent, time-dependent inhibitor of the enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.