Preparation of Optically Active Tertiary Alcohols by Enzymatic Methods. Application to the Synthesis of Drugs and Natural Products

By the catalysis of AK or porcine pancreas lipases, 3-iodo-2-phenyl-1,2-propanediol, 1-(hydroxymethyl)-1-phenyloxirane, 2-(iodomethyl)-4-phenyl-3-butyne-1,2-diol, 2-(iodomethyl)-4-(trimethylsilyl)-3-butyne-1,2-diol, and 5,5-dimethyl-2-(iodomethyl)-3-hexyne-1,2-diol were resolved in very high enantioselectivities (E >/= 153). The obtained enantiomerically pure or optically enriched compounds, containing an iodo atom, an oxirane moiety, or an alkynyl group, are versatile building blocks for the synthesis of chiral azido diols, sulfanyl diols, cyano diols, the side chain of a vitamin D(3) metabolite, the omega-chain of a prostaglandin analog, and an aggregation pheromone (1S,5R)-(-)-frontalin. Models based on the consideration of the importance of size, distance, and electron effect are proposed to interpret the observed stereospecificity in the enzymatic reactions. Thus, the lipase-catalyzed reactions of 1,1-disubstituted 1,2-diols occurred efficiently at the primary hydroxyl groups while the enantioselectivity was controlled by the tertiary carbinyl centers.