Synthetic approaches to steroidal alkaloids II. Preparation and reactions of 12-oxo-dinorcholanic acids

In a synthetic approach to the veratrum alkaloids, experiments directed toward the conversion of deoxycholic acid (I) to a 5 α -C-nor-D-homo-dinorcholan-22-oic acid (III) are described. Reaction of the diacetate of I with lead tetraacetate, gave 3 α, 12 α -diacetoxy-24-nor-5 β -chol-22-ene (VIII), which on periodate-permanganate oxidation afforded diactoxybisnordeoxycholic acid (IX). The olefin (VIII) was also obtained from I by a Curtius reaction, followed by methylation and Hofmann elimination. The stereochemistry at C-5 in this series was inverted by treating 3-oxo-12 α -acetoxy-23,24-dinor-5 β -cholan-22-oic acid (XI) with bromine, followed by dehydrohalogenation, metal ammonia reduction and sodium borohydride reduction to give the 5 α -isomer (XIII) of bisnordeoxycholic acid. The tosylhydrazones of the 12-ketones derived from XII and XIII were subjected to the Bamford-Stevens reaction and both compounds gave complex mixtures of olefins. A product from the reaction of XIII was a C-nor-D-homo lactone, (XV), which was characterized by principally spectroscopic methods.