Key structures for the synthesis of steroid antitumor agents. Synthesis of 16-dehydro-17-carbaldehydes of 13β- and 13α-estratriene series

A convenient preparative synthesis of 3-methoxyestra-1,3,5(10),16-tetraene-17-carb-aldehyde and its epimeric 13α-analog, the key structures in the synthesis of steroid estrogen receptor modulators and potential antitumor agents, was developed starting from estrone and including the generation of intermediate 16-dehydro-17-carbonitriles and their reaction with diisobutylaluminum hydride. The influence of conformational dif erences in the steroid molecules with the natural 13β- and epimeric 13α-configurations on the reactivity of intermediate compounds and the stereoselectivity of the trimethylsilyl cyanide addition to the carbonyl group of methyl ethers of epimeric estrones was considered.