FORMATION OF 14-ALPHA-CARDENOLIDES FROM 21-ACETOXY-20-KETO STEROIDS

The Emmons-Horner condensation of diethyl cyanomethylenephosphonate with 21-acetoxy-20-keto steroids has been studied. The reaction with 21-acetoxypregnenolone gives a 20-cyanomethylene steroid as a single isomer. The 3-enol ethers of deoxycorticosterone acetate, 11-dehydrocorticosterone acetate, and corticosterone diacetate react similarly. Δ1-Corticosterone acetate reacts directly with the ylide only at C-20 to form the corresponding 20-cyanomethylene derivative. These modified corticoids undergo ready dehydrogenation to form 1,4-, 4,6-, and 1,4,6-unsaturated ketones. When these cyanomethylene derivatives react with 1 equiv of p-toluenesulfonic acid in refluxing aqueous ethanol, transesterification of the 21-acetate and hydrolysis of the nitrile occurs to form a cardenolide ring in high yield. These mild conditions are compatible with a wide variety of other functional groups in the steroid. The corresponding cardanolides have been prepared by ketalization of the 3-ketone and subsequent hydrogenation and deketalization. © 1978, American Chemical Society. All rights reserved.