【作者】 刘丹丹；

【导师】 龚跃法；

【作者基本信息】 华中科技大学 ， 有机化学， 2009， 硕士

【摘要】 手性氨基醇是一类具有广泛应用前景的有机化合物,它们作为药物中间体、手性配体和手性合成砌块(building block)在药物合成、不对称合成等领域发挥着重要的作用。不对称还原α-取代β-氨基醛的动态动力学拆分是制备手性氨基醇的有效方法。本文首先设计并合成了一系列烷基取代的5-羟基异噁唑类半缩醛,然后考察了α-位取代基对半缩醛的酵母还原反应的影响。α-位取代基从较小体积的甲基依次替换为乙基和苄基,研究这三种取代基的酵母还原反应的活性,发现α-位的取代基越大,酵母还原越慢。另外,尝试采用手性催化剂来催化苯甲酰羟胺与烯醛的加成反应,产物用NaBH4还原后测e.e.值,发现并没有明显的对应体过量。接下来,将α-位无取代的半缩醛,分别利用D/L/DL-脯氨酰胺作为催化剂,用NCS对半缩醛进行氯代,得到不同构型过量的氯代半缩醛。先以外消旋的氯代醛为底物,考察了不同条件下的酵母还原反应,然后在最佳条件下对不同构型过量的醛进行酵母还原,测定产物的e.e.值。在5-羟基异噁唑类半缩醛的面包酵母还原反应的研究中,发现α-位取代基与电负性均对5-羟基异噁唑类半缩醛的酵母还原反应有较大影响,α-甲基半缩醛可以被酵母完全还原,但产物e.e.值仅为13%,α-乙基半缩醛有63%的e.e.值,但是转化率只有60%左右。α-氯代半缩醛经酵母还原后不仅可以完全转化,且得到了最高76%的e.e.值。更多还原

【Abstract】 Chiral amino alcohols are wildly used organic compounds. They play important roles in pharmacy and asymmetric synthesis as intermediates, building blocks and chiral ligands.Dynamic kenrtic resolution (DKR) via the reduction ofα-branched-β-amino- aldehydes presents an efficient way to chiral amino alcohols.Firstly, a series of novel alkyl-substituted-5-Hydroxyl-isoxazolidine hemiacetals were synthesized, and then the effects ofα-substituents towards the baker’s yeast’s reduction were estimated. It was found that the bulkier the substituents were,the slower the bioreduction rate was. In addition, chiral catalysts were employed to catalyze the addition of benzoylhydroxylamines to aldehydes, but no enantiomer excess was detected.In the following study,α-chloral hemiacetals were synthesized via chlorination ofα-unbrached hemiacetals catalyzed by D/L/racemic prolineamide. Then, the reduction of aldehydes with different configuration was investigated.During the study of baker’s yeast mediated bioreduction of isoxazolidine-derived hemiacetals,It was indicated that both the bulky and the electronegativity ofα-substituent were found to show great effet on the reaction. In the case ofα-methyl hemiacetal, it can be totally converted but the e.e. value of the product was only 13%, while theα-ethyl hemiacetal was limited to 60% conversion, albeit with 63% e.e. Theα-chloral hemiactal give the best results totally conversion and 76%e.e.更多还原