Synthetic studies on fusicoccin A: Enantioselective synthesis of the C-ring fragment

The enantioselective synthesis of the C-ring fragment of fusicoccin A is described. The TBS ether of hydroxyketone prepared by baker's yeast reduction was converted to the alpha-ethylidene ketone by aldol condensation with propionaldehyde, followed by Michael reaction with divinylcopper reagent and conversion to enol triflate to afford a single diastereomer. X-ray crystallographic analysis of the crystalline derivative of the single diastereomer showed that the asymmetric carbon formed by the Michael reaction was consistent with the configuration of the C15 asymmetric carbon of fusicoccin A. The vinyl group of the enol triflate was converted to a hydroxymethyl group by selective dihydroxylation with a bulky ligand, oxidative cleavage of the resultant 1,2diol with lead tetraacetate, and DIBAL-H reduction. The hydroxymethyl group was subsequently converted to TBS ether, followed by the hydrogenolysis of the benzyl group and Dess-Martin oxidation, accomplishing the enantioselective synthesis of the desired C-ring fragment of fusicoccin A.