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

1.利用面包酵母合成手性内酯面包酵母还原3-烷基化-γ-丁烯内酯得到高光学纯度的手性γ-丁烯内酯。面包酵母还原3-苯硫基甲基丁烯酰亚胺得到（R）-3-苯硫基-甲基-γ-丁烯酰亚胺（99%ee），这是一种用于萜烯合成的通用手性结构单元。3-苄氧基甲基-γ-丁烯酰亚胺类似反应生成（S）-3-苄氧基甲基丁烷酰亚胺（95%ee），其转化为S.同时检测了绿色染色体。天然α-生育酚的不对称合成采用化学酶法合成了（2 R，4 'R，8' R）-α-生育酚。通过脂肪酶催化水解前手性1，3-二乙酸酯合成了色满部分，得到的单酯光学纯度为67%ee;<15>通过脂肪酶催化酯交换C_5前手性1，3-二醇得到了C_侧链，光学纯度为95%ee.海绵中的（S）-variabilin的不对称合成首次从Ircinia variabilis中分离得到抗菌的（S）-variabilin，通过两条路线通过脂肪酶催化的前手性1，3-二醇的不对称酯交换反应完成。不对称诱导法合成variabilin的关键中间体2-羟甲基-4-苯硫基-1-丁醇的光学纯度为99%ee.链霉菌中抗生素自身调节因子的不对称合成。virgiae，通过化学酶法完成。在本工作的过程中，发现前手性2-酰胺乙基-1，3-丙二醇在脂肪酶催化下的酯交换反应得到了高光学纯度的手性单酯，并且单酯的绝对构型依赖于酰胺基。

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.