Development of Enzymatic Method for Asymmetric Induction and Its Application for Natural Products Synthesis

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1. Synthesis of chiral lactones using bakers' yeast Bakers' yeast reduction of 3-alkylated-gamma-butenolides gave chiral gamma-butanolides with high optical purity in good yield. Bakers' yeast reduction of 3-phenylthiomethylbutenolide afforded (R)-3-phenylthio-methyl-gamma-butanolide (99%ee), a versatile chiral building block for terpene synthesis. Similar reaction of 3-benzyloxymethyl-gamma-butenolide gave (S)-3-benzyloxymethylbutanolide (95%ee), and its transformation to factor-I, the autoregulator of S. viridocchromogenes, was also examined.2. Asymmetric synthesis of natural alpha-tocopherol The formal synthesis of (2R,4'R,8'R)-alpha-tocopherol was achieved using chemoenzymatic process. The chroman part was synthesized via lipase-catalyzed hydrolysis of prochiral 1,3-diacetate and the optical purity of the monoester obtained was 67%ee. On the other hand, the C_<15> side chain was obtained in 95%ee via lipase-catalyzed transesterification of C_5 prochiral 1,3-diol.3. Asymmetric synthesis of variabilin, furanosesterterpene in sponge The first synthesis of antibacterial (S)-variabilin, isolated from Ircinia variabilis was accomplished via two routes by lipase-catalyzed asymmetric transesterification of prochiral 1,3-diols. The optical purity in asymmetric induction to 2-hydroxymethyl-4-phenylthio-1-butanol, the key intermediate of variabilin synthesis, was 99%ee.4. Asymmetric synthesis of the autoregulator of antibiotics in Streptomyces Virginia butanolide C, virginiamycin inducing factor of S. virgiae, was accomplished via chemoenzymatic process. In the course of this work, it was found that lipase-catalyzed transesterification of prochiral 2-amidoethyl-1,3-propanediols gave the chiral monoesters with high optical purity and the absolute configuration of the monoester was dependent on the amide group.