Baker's Yeast Mediated Asymmetric Reduction of Ketones Having Sulfur Functional Groupes and Application to the Natural Product Synthesis

在酮的-位上引入含硫官能团<alpha>可以显著提高面包酵母的底物专一性，从而在面包酵母介导的酮的不对称还原反应中获得高的光学活性仲醇的化学产率和光学产率。此外，通过利用硫官能团，还原产物已被有效地用作各种光学活性天然产物的有用手性配体。将3-氧代-2-硫基酯还原得到光学纯的（3S）-3-羟基-2-硫基酯。2-将取代的3-氧代二硫代酯非对映选择性还原，得到（2 R，3S）-顺式-2-取代的3-羟基酯。(2R将酵母还原2-甲基-3-氧代丁二酸甲酯得到的（2S，3S）-3-羟基-2-甲基丁二酸二乙酯转化为松叶蜂信息素（2S，3S，7S）-2-乙酰氧基-3，7-二甲基十五烷。3-羟基-1-苯硫基-2-丙酮的还原产物（S）-3-苯硫基-1，2- 关于我们 丙二醇转化为（S）-缩水甘油基硫醚，后者是合成R和S光学活性仲醇和2-羟基醛的有用手性合成子。以硫代缩水甘油醚为原料，经短步骤合成了东方胡蜂信息素、5-十六碳十六醇、L-玫瑰糖和D-甘露糖等脱氧糖。<alpha>用酵母还原-（1，3-二噻烷-2-基）酮，得到相应的（S）-<alpha>-羟基二噻烷。由此获得的（S）-1-（1，3-二噻烷-2-基）-1，4-丁二醇被有效地转化为从灰色链霉菌分离的（4S，5S）-和（4S，5 R）-5-二羟基癸烷-4-内酯。在-位上具有1，3-二噻烷、苯硫基或苯磺酰基的1，2-二酮的还原<alpha>进行非对映选择性地得到高对映体过量的（S，S）-反式-1，2-二醇。这些1，2-二醇衍生物是多醇天然产物如从Amitamuscarin中分离的L-毒蕈碱、（4 R，5S）-5-羟基-2-己烯-4-酮（作为黄蝶幼虫的拒食剂）和L-洋地黄毒糖的有用手性配体。1-（1，3-二噻烷-2-基）-1，3-丁二酮经还原得到（S，S）-1，3-二醇，再经短步骤转化为壬酸甲酯。此外，具有硫官能团的异戊二烯醛或醇的碳-碳键被酵母还原，以提供饱和异戊二烯衍生物，其是有用的手性配体的各种光学活性萜类化合物。少

Introduction of sulfur functional groups to <alpha> -positions of ketones has been found to improve remarkably the substratespecificity of baker's yeast to result in high chemical and optical yields of the optically active secondary alcohols in the baker's yeast mediated asymmetric reduction of ketones. Further the reduction products have been effectively employed as useful chiral synthons for various kinds of optically active natural products by utilizing the sulfur functional groups. The reduction of 3-oxo-2-sulfenyl esters afforded optically pure (3S)-3-hydroxy-2-sulfenyl esters. 2-Substituted 3-oxo dithioesters were diastereoselectively reduced to give (2R,3S)-syn-2-substituted 3-hydroxy esters. (2R,3S)-3-Hydroxy-2-methylbutanedithioate obtained by the yeast reduction of methyl 2-methyl-3-oxobutanedithioate was converted to the pheromone of pine saw fly, (2S,3S,7S)-2-acetoxy-3, 7-dimethylpentadecane. The reduction product of 3-hydroxy-1-phenylthio-2-propanone, (S)-3-phenylthio-1,2- … More propanediol, was converted into (S)-glycidyl sulfide which was a useful chiral synthon for both R and S optically active secondary alcohols and 2-hydroxy aldehydes. The pheromone of Vespa Orientals, 5-hexadecanolide, deoxy sugars such as L-rhodinose and D-amicetose were synthesized in short steps from the glycidyl sulfide. <alpha> -(1,3-Dithian-2-yl)ketones were reduced by the yeast to afford the corresponding (S)- <alpha> -hydroxy dithianes. (S)-1-(1,3-Dithian-2-yl)-1, 4-butanediol thus obtained was effectively converted into (4S,5S)- and (4S,5R)-5-dihydroxydecan-4-olides isolated from Streptomyces griceus. The reduction of 1,2-diketones having 1,3-dithiane, phenylthio or phenylsulfonyl group at the <alpha> -position proceeds diastereoselectively to give the (S,S)-anti-1,2-diols in high enantiomeric excess. These 1,2-diol derivatives were useful chiral synthons for poly-ol natural products such as L-muscarine isolated from Amonita muscarin, (4R,5S)-5-hydroxy-2-hexen-4-olide as antifeedant for the larvae of the yellow butterfly, and L-digitoxose. The reduction of 1-(1,3-dithian-2-yl)-1,3-butanedione gave the (S,S)-1,3-diol which was converted into methyl nonactate in short steps. Further, the carbon-carbon bonds of prenyl aldehydes or alcohols possessing sulfur functional groups were reduced by the yeast to afford saturated isoprene derivatives which were useful chiral synthons for various optically active terpenoids. Less