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
, (
4
R,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 (
4
R,5S)-
22
(49.7%, >99%ee) and acetate (
4
S,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 (
4
S,5S)-21 which was converted into ketal (
4
R,5S)-27 via three steps. The coupling reaction of methyl
4
,5-epoxy-(2
E
)-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.
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