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. It is a leading disorder of the elderly male population. Excessive production of dihydrotestosterone has been implicated in this pathological condition. Steroidal 5α-reductase is a membrane bound NADPH dependent enzyme which is responsible for the conversion of testosterone (T) to dihydrotestosterone (DHT). Therefore, inhibition of production of DHT by 5α-reductase inhibitors 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, Marker degradation, oximation and Beckmann rearrangement. 17-Oxo-3, 5- seco-keto acid was then converted to 17-oxo-17a-aza-D-homo-3, 5-seco-4-nor-androstan-3-oic acid by oximation followed by Beckmann rearrangement. The resulted seco-keto acid was then treated with thionyl chloride and the respective amines and phenols to get the desired 3, 5-seco-steroidal amides (17-18) and esters (19-20) respectively.