L-脯氨酰-L-亮氨酰-甘氨酰胺(PLG)三肽合成

Synthesis of tripeptide L-prolyl-L-leucyl-glycinamide

L-脯氨酰-L-亮氨酰-甘氨酰胺三肽,具有重要的生理药理作用,可用于治疗帕金森病。以L-脯氨酸、L-亮氨酸和甘氨酰胺为原料,采用混合酸酐法,以苄氧羰基(cbz)为氨基保护基,以氯甲酸异丁酯为成酸酐试剂,以Pd/C催化氢解脱除cbz基合成了L-脯氨酰-L-亮氨酰-甘氨酰胺三肽,并进一步优化了合成条件:L-cbz-pro的最佳工艺条件为n(cbz)/n(L-pro)=2.6/1,反应温度-5℃,反应时间2h;L-cbz-prolyl-L-leu的最佳工艺条件为,反应温度-10℃。在上述工艺条件下产品总收率38.5%,光学纯度98.7%,熔点120～122℃,[α]D20=-46.3°。

Tripeptide L-prolyl-L-leucyl-glycinamide （PLG） has important physiological and pharmacological functions, and can be used to treat Parkinson＇s disease. PLG was synthesized by using the mixed anhydride method from L-proline, L-leucine and glycinamide. The amino groups of L-proline and L-leucine were protected firstly by the carbobenzoxy group, and then the carbobenzoxy group was removed by Pd/C with 1-12 from L-cbz-prolyl-L-leulyl-gly -NH2 to produce PLG in the end. Isobutyl chloroformate was used as reagent to form mixed anhydride. The optimum conditions to synthesize L-cbz-pro and L-cbz-prolyl- L-leu, were n（cbz）ln（L-pro）=2.6：1 at -5 ℃ for 2 hours and n（i-C4H9OCOC1）/n （L-cbz-pro）=1：1 at -10℃ respectively. Under these conditions, the melting point, optical purity and total yield of PLG were 120- 122℃, 98.7% and 38.5% respectively. The specific rotation [α]^D20==-46.3°.