New Synthesis of Castasterone

An improved synthesis that could produce gram quantities of castasterone was proposed. The starting material was stigmasterol, the cyclic part of which was transformed in the first synthetic step into the 3 alpha,5-cyclo-6-ketone. The side-chain carbon skeleton in the target compound was constructed with the required stereochemistry of the C-24 methyl via addition of methylacetylene, hydrogenation of the propargyl alcohol over Lindlar catalyst, and Claisen rearrangement. Diols were introduced using Sharpless asymmetric dihydroxylation of the intermediate a dagger(2,22)-dienone in the presence of (DHQD)(2)AQN. A unique feature of the synthesis was the avoidance of chromatographic separations of propargyl alcohols with similar chromatographic mobilities because the C-22 diastereomers were enriched in subsequent redox reactions.