4-去乙酰化长春碱氨基酸衍生物的合成

Synthesis of 4-deacetylvinblastine amino acid analogues

目的:合成4-去乙酰化长春碱氨基酸衍生物,为长春碱靶向前药的合成奠定基础。方法:氨基酸N端采用苄氧羰基(Z)保护,利用混合酸酐法合成(4-去乙酰化长春碱)-氨基酸-Z,然后催化氢化得到(4-去乙酰化长春碱)-氨基酸衍生物。结果:采用新方法合成4-去乙酰化长春碱氨基酸衍生物,结构经质谱和1H-NMR确证。结论:本实验所采用的方法通用性强,优化了反应条件,反应步骤缩短,产率高,产物后处理简便,降低了实验成本。

Objective：To synthesize 4-deacetylvinblastine amino acid analogues, and to supply key synthetic methods for vinblastine prodrugs. Methods： Amino acids were protected by Z groups at N-terminal coupled with 4-deacetylvinblastine using the mixed anhydride method, and then deprotected by catalytic hydrogenation to obtain target compounds. Results： 4-Deacetylvinblastine amino acid analogues were successfully synthesized and conformed by ESI-MS and 1H-NMR. Conclusion： The more applicable synthetic method can optimize the synthetic process and is suitable for synthesis of 4-deacetylvinblastine amino acid analogues.