Stereoselective asymmetric synthesis and characterization of 17α-acetyoxy-19-nor-progesterone

Abstract

17α-actoxy-19-nor-progesterone was synthesized by a new efficient stereoselective asymmertric pathway from 19-nor-androst-4-en-3, 17-dione in 5-steps reactions with overall yield 63.3%. Consequently, a strategy was used to produce of 17-α-hydroxyl compound stereoselectively by addition 17-keto steroid with hydrogen cyanide, at the same time, the conditions of this asymmertric reaction were optimized. The titled compound and the intermediate were fully characterized by ¹H, one dimension and two dimension ¹³C-nuclear magnetic resonance, and infrared spectrum. The results show that the rate of 17-α-hydroxyl compound isomeride is sensitively affected by the solution system and the best volume ratio of CH₃OH to H₂O is 36%. After the carbonyl and hydroxyl groups were protected by ethylenediol and vinyl butyl ether respectively, organometallic addition to CN group with CH₃Li, androstance compound was converted to pregnane compound. After removing the protective groups by a mild hydrolytic procedure with high yield, the titled compound was obtained by esterified the above intermidiate. The new pathway gives a good purity of 98% as determined by high performance liquid chromatography.

Keywords

17α-acetoxy-19-nor-progesterone / synthesis / ¹³C-nuclear magnetic resonance / steroid