一种腐霉利衍生物的设计与合成

Design and Synthesis of A Putrescine Derivative

含羧基基团的腐霉利衍生物,其羧基能够与蛋白质分子发生酰化或重氮化反应,能够对农药残留快速进行分析检测,在食品安全领域具有潜在应用价值。以2-氯丙酸甲酯和甲基丙烯酸甲酯为原料,通过亲核取代、酯水解、脱水反应、烷基化、硝基还原、氨基酰基化、酸胺缩合和三氟乙酸水解8步反应合成了腐霉利半抗原衍生物,其结构经^(1)H NMR,^(13)C NMR和MS(ESI)表征,并对其关键的合成工艺进行优化。结果表明:2-氯丙酸甲酯和甲基丙烯酸甲酯的反应时间为96 h时,亲核取代反应的收率最高为70%。硝基还原过程中,以二氯亚锡水合物作还原剂,且二氯亚锡水合物与中间体8的物质的量之比为4.0∶1.0时,硝基还原反应收率最高为63%。当化合物5和化合物9的物质的量之比为1.5∶1.0,且反应温度为85℃时,氨基酰基化反应最高收率为50%。

The carboxyl group of humus derivatives can acylation or diazotization with protein molecules,which can quickly analyze and detect pesticide residues,and has potential application value in the field of food safety.Using methyl 2-chloropropionate and methyl methacrylate as raw materials,the humus hapten derivatives were synthesized through an 8-step reaction of nucleophilic substitution,ester hydrolysis,dehydration,alkylation,nitro reduction,amino nucleophilic substitution,acid amine condensation and trifluoroacetic acid hydrolysis.Their structures were characterized by ^(1)H NMR,^(13)C NMR and MS(ESI).The key synthesis process was optimized.The results showed that the reaction time of methyl 2-chloropropionate and methyl methacrylate was 96 h.The yield of the nucleophilic substitution reaction was up to 70%.In the nitro reduction process,when dichlorostannous hydrate was used as the reducing agent and the ratio of the amount of dichlorostannous hydrate to the amount of intermediate 8 was 4.0∶1.0,the nitro reduction reaction yield was the highest 63%.The maximum yield of aminoacylation was 50%when the ratio of compound 5 to compound 9 was 1.5∶1.0 and the reaction temperature was 85℃.