The synthesis of 16-dehydropregnenolone acetate (DPA) from potato glycoalkaloids

The use of solanidine as starting material for the synthesis of steroid hormones was strongly stimulated by the possibility to isolate large amounts ( ton scale) of potato glycoalkaloids from a waste stream of the potato starch production. A procedure is available to isolate these glycoalkaloids from the potato protein fraction and after hydrolysis solanidine is set free and can be made available as alternative for diosgenine as starting material for the production of dehydropregnenolon acetate (DPA). The conversion of solanidine to DPA was first tried by reinvestigation of several known methods like oxidation with Hg(OAc)(2), the Cope reaction and the Polonovski reaction but none of these approaches were successful. The best option was to open the E,F-ring system using the Von Braun reaction. Besides the desired major E-ring opened compound also the minor F-ring opened compound was isolated. Alternatives for the hazardous Von Braun reagent BrCN were investigated but not found. Further degradation using the Hofmann reaction was successful in a Delta(16) derivative, which led to the desired triene intermediate. Finally DPA could be obtained starting from solanidine in 9 reaction steps in 30% overall yield using the known conversion to spirosolane compounds followed by conversion to DPA. Extensive research has been performed on finding shortcuts in this route but despite all our efforts, further shortening of the route from 3-acetoxysolanidine via tomatidenol to DPA could not be accomplished.