19-Norsteroids of Unnatural Configuration from Ergosterol

A new method for the preparation of a 19-norsteroid of unnatural configuration from ergosterol has been described. This method led to the preparation of 5α,8α,9α,10α-19-norpregnan-3,20-dione which possesses unnatural configuration at positions 8 and 10. The following reaction sequence was utilized to prepare this steroid. Ergosterol was photo-oxidized to give bisergostatrienol that was pyrolyzed to yield neoergosterol whose side chain was cleaved by ozonolysis to yield 3β-hydroxy-19-norpregna-5,7,9(10)-20α-aldehyde. This aldehyde, for the first time obtained in a crystalline state, was degraded via ozonolysis of the 3β-hydroxy-20-morpholino-methylene-19-norpregna-5,7,9(10)-triene derivative to give 3β-hydroxy-19-norpregna-5,7,9(10)-triene-20-one. The latter was reduced to the corresponding diol with Ru/carbon, and its Ring B in turn successfully hydrogenated in cyclohexane with Rh/alumina as the catalyst. The diol was oxidized to the diketone with the Jones reagent. Although some of the above transformations previously have been recorded, this report describes marked improvements in the techniques and yields of most of the intermediates.