手性卤代醇的化学-酶法合成研究
毕业论文关键字：手性醇；生物催化剂；不对称还原；手性药物
Study on the chemo-enzymatic synthesis of chiral halogen alcohols
Abstract: Chiral halohydrin with specific functional groups is an important intermediate in the synthesis of chiral drugs and other chiral chemicals. Chiral halohydrin can synthesize a large number of chiral drugs. Halohydrin mature synthesis of chiral synthesis of chiral drugs and improve a positive role in promoting. Preparation of chiral halohydrin compound present mainly by chemical and biological methods. This study in mild conditions for the use of halogenated reagents acetophenones halogenated compounds synthesized side chain haloketones, and in the "pot" on the use of microbial carbonyl reductase catalytic asymmetric reduction haloketones Synthesis of Chiral halohydrin drug intermediates. Chemical halogenation of acetophenone on the solvent NBS, adding method and amount of toluene sulfonic acid effect of alpha halogenated phenyl ethyl ketone yield, the optimum reaction conditions: when the NBS in the total amount of 1.2 times the equivalent of substrate. On this basis, the pH of the reaction fluid is 7, and the asymmetric reduction of the to the yeast cells is (R) - methyl alcohol, the yield is 99%, the EE value is above 96%
Key Words：Chiral alcohols; biocatalyst; asymmetric reduction; chiral drugs
目 录
1 研究背景 1
1.1 手性合成的研究意义 1
1.1.1 手性合成在制药领域中的应用 1
1.1.2 手性合成在其他领域的应用 2
1.2 获得手性化合物的方法 2
1.2.1 手性源 2
1.2.2 不对称合成 3
1.2.3 外消旋体拆分 3
1.3 手性在制药领域中的应用 4
1.4手性合成在其他领域的应用 5
1.4.1 研究意义 5
1.4.2 研究思路 6
2 实验原理和流程 8
2.1实验原理 8
2.1.1生物催化法制备手性化合物 8
2.1.2 生物催化羰基还原反应原理 8
2.1.3 生物催化法合成手性醇类化合物 10
2.2 实验方案的确定 11
3 试验方法与材料 12
3.1 实验材料 12
3.1.1 菌种 12
3.1.2 培养基 12
3.1.3 主要试剂 12
3.1.4 主要仪器 13
3.2 试验方法 13
3.2.1 Rhodotorula sp. AS2.2241细胞的发酵培养 13
3.2.2芳基酮化合物的化学卤代 13
4 实验结果和讨论 17
4.1 标准曲线 17
4.2反应体系的确定 17
4.3分批补加NBS对反应的影响 18