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

不对称诱导酶法的发展及其在天然产物合成中的应用

基本信息

批准号：
03805075
负责人：
TAKABE Kunihiko
金额：
$ 1.02万
依托单位：
SHIZUOKA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

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.

1。使用面包师的酵母面包师酵母降低3-烷基化γ-丁二醇的酵母菌的合成，从而使手性γ-叔丁醇具有较高的光学纯度，其产量良好。酵母减少3-苯基硫甲基丁苯甲酸（R）-3-苯基噻吩基 - 甲基 - 甲基 - 丁二醇（99％EE），这是一种用于萜烯合成的多种手性手性构建块。 3-苯甲酰甲基甲基 - 丁二醇的相似反应得出（S）-3-苯甲酰氧基甲基丁二醇（95％EE），并且还检查了其转化为viridocchromogenes链球菌的自动基因，也检查了其转化为I。天然α-生育酚的不对称合成（2r，4'r，8'r） - 阿尔法托酚的形式合成是使用化学酶过程实现的。通过脂肪酶催化的1,3-二乙酸盐的脂肪酶催化的水解合成Chroman部分，获得的单酯的光纯度为67％EE。另一方面，通过脂肪酶催化的C_5疗程1,3-二醇的脂肪酶催化的持续酯在95％EE中获得C_ <15>侧链。3。差异蛋白的不对称合成，在海绵中的Furanosesterpene的不对称合成是通过脂肪酶 - 催化的两种途径通过两种途径完成了从Ircinia variabilis中分离出的抗菌（S） - 瓦ariabilin蛋白的首次合成，这是通过脂肪酶促进的非对称的proChiralsationalsized降低了1,3-二醇的非对称的不对称的。对2-羟基甲基-4-苯基硫硫醇-1-丁醇的不对称诱导的光纯度（差异蛋白合成的关键中间体）为99％EE.4。通过化学酶过程完成了弗吉尼亚丁醇C抗生素自动调节剂的不对称合成，弗吉尼亚丁醇C，牙霉素诱导因子的牙氨基霉素C的不对称合成。在这项工作的过程中，发现脂肪酶催化的2-氨基乙基-1,3-丙二醇的脂肪酶的式持续化为手性纯度提供了高光学纯度，单酯的绝对构型依赖于酰胺组。