【作者】 黄丽琴；

【导师】 杨红；

【作者基本信息】 南京农业大学 ， 农药学， 2003， 硕士

【摘要】 N-酰基丙氨酸类化合物是一类高效、低毒内吸性杀菌剂。对由霜霉、畸雌腐霜、葡萄霜霉病等引起的植物病害有较好的防治效果。这类化合物的结构通式如下： 从结构式可以看出，该类杀菌剂属苯基酰胺类化合物。N-C(C)-C骨架是其活性骨架，含一个手性碳原子，有一对对映体，R-(-)-异构体的杀菌活性比S-(+)-异构体高。N-(2，6-二甲苯基)-丙氨酸甲酯足其最重要的中间体。 以α-氯代丙酸为原料，两步反应制备N-(2，6-二甲苯基)-丙氨酸甲酯，合成收率分别为90％、92％，产品纯度均≥95％。 碱性拆分剂R-(+)-α-异丙基对氯苄胺、S-(-)-α-甲基苄胺、L-辛可宁、L-(+)一N，N---~甲基氯霉胺为拆分剂，用化学法拆分N一(2，6-----甲苯基)-丙氨酸甲酯，最终选择S-(-)-α-甲基苄胺为拆分剂，拆分效果好，S-(-)-α-甲基苄胺回收率为92％。R-(+)、S-(-)-N-(2，6-二甲苯基)-丙氨酸与L-薄荷醇成酯，传统HPLC分析光学纯度。J-(+)-N-(2，6-二甲苯基)-丙氨-酸光学纯度≥98％，S-(-)-N-(2，6-二甲苯基)-丙氨酸光学纯度为55.4％。 用Candida rugosa lipases(CRL)，脂酶拆分N-(2，6-二甲苯基)-丙氨酸甲酯，分别从pH、酶量、助剂、转速、温度这几个方面优化酶促反应条件。最终确定最适酶促反应体系：pH 6.4，酶量250mg，助剂2g，聚乙二醇(PEG)，转速160 r.p.m，温度35℃。温度、酶量对反应体系影响较大。CRL脂酶对S-(-)-N-(2，6-二甲苯基)-丙氨酸甲酯作用速度远大于R-(+)-异构体。反-应后分离得到R-(+)-N-(2，6-二甲苯基)-丙氨酸甲酯。它是N-酰基丙氨酸类化合物的光学活性中间体，和酰氯反应即得光学活性N-酰基丙氨酸类化合物。HPLC跟踪反应转化率、产品光学纯度，该方法未见报道。化学拆分法需四步反应才可制备R-(+)-N-(2，6-二甲苯基)-丙氨酸甲酯，需大量溶剂，光学拆分剂；相比之下，酶法拆分一步即可完成，且反应条件温和、溶剂用量少、无毒。更多还原

【Abstract】 N-Acylalanines belong to a series of syatemic fungicides with high biological activity and low mammal toxicity. They posses the natures of prevention and care of plant diseases caused by Pythium irregulars, Plasmopara viticola and Zoospores germination. The general structure of the N-Acylalanines as fungicides is following:N-C(C)-C in the molecular structure is the funficidally active radical. It has one chiral C and a pair of enantiomeric isomers. The activity of R-isomer is higher than that of S-isomer. N-(2,6-xylyl)-alanine is the most important intermediates of N-Acylalanines.Methyl N-(2, 6-xylyl)-alanine was prepared from -chloropropionic acid. The yields of the two reactions are 90% and 92%, respectively. The chemical purities of the product are more than 95%.Chiralreagents, such as S-(+)- - phenylethylamine, L-cinchonine , L-(+)-N, N-dimethyl-4-nitrophenyl- -hydrox-isobutylamine and R-(+)-4-chlorophenyl -isobutylamine were used for the resolution of methylN-(2, 6-xylyl)-alanine. Among those, S-(+)- -phenylethylamine gave the best one with the recovery of 92%. Optical isomers of N-(2,6-xylyl)-alanine were used for preparing their L-menthol ester, which could be resoluted and determined on an ordinary column by HPLC. The optical purity of R-(+)-N-(2, 6-xylyl)-alanine was more than 98%, that of S-(-)-isomer is 55.4%.Methyl N- (2,6-xylyl)-alanine is resoluted by Candida rugosa lipases (CRL).The reaction is optimized from pH, amounts of lipase, subsidiary, stirring speed of shaker bath and temperature. Under theconditions of pH 6. 4, amounts of lipase 250mg, PEG of 2g, the stirring speed 160 r.p. m and the temperature 35 C, the best results were obtained. Temperature and amounts of lipase were more important than the others. CRL was reacted much more quickly with methyl 5-N-(2, 6-xylyl)-alanate than that with R isomer. Thus, methyl R-N-(2, 6-xylyl)-alanate was given from reacted liquid, which was the intermediate with optical activity we need. Optical active N-acylalanines were prepared from methyl R-N-(2, 6-xylyl)-alanate. The convertion and enantiomeric excess was determined by HPLC.Compared with chemical resolution, which need four reactions, a number of solvents, the resolution by CRL can be finished with only one reaction, milder condition and less solvents.更多还原