synthesis of novel 17-oxo-17a-aza-d-homo-3, 5-seco-steroids as potential 5α-reductase inhibitors

benign prostatic hyperplasia (bph) is a non-malignant enlargement of the prostate gland. itis a leading disorder of the elderly male population. excessive production of dihydrotestosteronehas been implicated in this pathological condition. steroidal 5α-reductase is a membrane boundnadph dependent enzyme which is responsible for the conversion of testosterone (t) todihydrotestosterone (dht). therefore, inhibition of production of dht by 5α-reductaseinhibitors is an important approach for the treatment of bph. the proposed 17-oxo-17a-aza-dhomo-3,5-seco-steroids (17-20) have been synthesized using diosgenin as the starting material.diosgenin was converted to 17-oxo-3, 5-seco-4-nor-androstan-3-oic acid following six steps:oppenauer oxidation, lemieux-von rudloff oxidation, wolff-kishner reduction, markerdegradation, oximation and beckmann rearrangement. 17-oxo-3, 5- seco-keto acid was thenconverted to 17-oxo-17a-aza-d-homo-3, 5-seco-4-nor-androstan-3-oic acid by oximationfollowed by beckmann rearrangement. the resulted seco-keto acid was then treated with thionylchloride and the respective amines and phenols to get the desired 3, 5-seco-steroidal amides (17-18) and esters (19-20) respectively.