One of the most efficient method to synthesize optically pure natural products is to start off with chiral synthon. We synthesized three new chiral synthons (2R,3R)-4, (4R,5S)-27, and (S)-(-)-34 on the basis of the following two concepts; (1) to utilize the highly stereoselective chemical method to establish the relative configuration, (2) to carry out the kinetic resolution of racemates by ester-cleaving enzymes (lipase) at the next step. The Zn(BH_4)_2 reduction of β-keto ester (±)-3 afforded the alcohol (±)-syn-1 in high diastereoselectivity. The saponification of the corresponding acetate (±)-4 using the lipase "Amano A" proceeded enantioselectively to give acetate (2R,3R)-4 (48% yield, >99%ee) and alcohol (2S,3S)-1 (51% yield, 94%ee). The epoxidation of methyl sorbate followed by addition of thiophenol provided (±)-22 stereospecifically. The enantioselective esterification of (±)-22 using the lipase "PL266" in the presence of isopropenyl acetate gave alcohol (4R,5S)-22 (49.7%, >99%ee) and acetate (4S,5R)-23 (50.2%, 98%ee). The successful conversion of C-S into C-O bond at C_4 chiral center in stereo retentive manner was carried out to give (4S,5S)-21 which was converted into ketal (4R,5S)-27 via three steps. The coupling reaction of methyl 4,5-epoxy-(2E)-pentenoate 33 and m-methoxy toluene in the presence of lewis acid provided two alcohols 34 (23%) and 35 (49%). The enantioselective hydrolysis of acetate (±)-36 derived from 34 using the lipase "MY-30" gave alcohol (S)-(-)-34 (85%ee). The enzymatic esterification of this chiral compound using same lipase achieved the enrichment of optical purity. In result, we obtained (S)-(-)-36 (94%ee). These chiral compound were applicable to the syntheses of (-)-Oudemansins A, B and X, L-Acosamine, and (S)-(+)-Curcudiol.
