Synthesis of 9-methyl-19-norsteroids

Abstract

Alkylation of an 11-oxoestrone derivative (I) has been shown to give a 9α-methyl product which could be further transformed into 9α-methyl-19-nor-compounds. A 9β-methyl-11-oxoestrone has been converted into 9β-methylestrone 3-methyl ether and a synthesis of 9β-methyl-19-norsteriods has been developed using as a key step the reaction of lithium dimethylcuprate with the secosteroid, 3,3-ethylenedioxy-17β-hydroxy-4,5-secoestr-9-en-5-one (XXXIV). Reaction of this same secosteroid with diethylaluminium cyanide led to the 9α-cyano-compound as the major product, as demonstrated by transformation of the cyano-group into a methyl substituent and comparison of the derived tetracyclic structure with 9-methyl steroids of proven stereochemistry.