【摘要】 本文叙述带保护基的牛胰岛素A链氨端五肽Ⅰ(N-苄氧羰基甘氨酰-异亮氨酰-缬氨酰-γ-叔丁酯谷氨酰-谷氨酰胺酰肼基甲酸叔丁酯)及九肽Ⅱ(N-苄氧羰基甘氨酰-异亮氨酰-缬氨酰-谷氨酰-谷氨酰胺酰-S-苄基半胱氨酰-S-苄基半胱氨酰-丙氨酰-丝氨酰脐)的合成。Ⅰ是由已知三肽Ⅲ(N-苄氧羰基异亮氨酰-缬氨酰-γ-叔丁酯谷氨酸乙酯)经二种不同的合成步骤分别缩合而得,五肽Ⅰ经三氟乙酸脱去γ-叔丁基和N-叔丁氧羰基后与已知四肽Ⅷ(S-苄基半胱氨酰-S-苄基半胱氨酰-丙氨酰-O-乙酰丝氨酸甲酯溴氢酸盐)借迭氮法缩合而得九肽酯Ⅸ再经肼解而得九肽肼Ⅱ。合成的三肽、四肽、五肽和九肽的化学纯度曾经纸层析、纸电泳、元素分析及氨基酸组成分析证明,其光学纯度(除九肽Ⅱ和Ⅸ外)皆曾经亮氨酸氨肽酶水解及水解物的氨基酸组成测定证明为L型,九肽Ⅸ是由光学纯L型的肽Ⅰ与Ⅷ经迭氦法缩合而成,因此Ⅸ以及Ⅱ很可能为光学纯L型。更多还原

【Abstract】 The present paper deals with the synthesis of peptide Ⅰ(N-carbobenzoxyglycyl-L-isoleucyl-L-valyl-γ-tert-butyl-L-glutamyl-L-glutamine carbo-tert-butoxyhydrazide) and peptide Ⅱ (N-carbobenzoxyglycyl-L-isoleucyl-L-valyl-L-glutamyl-L-glutaminyl-S-benzyl-L-cysteinyl-S-benzyl-L-cysteinyl-L-alanyl-L-serine hydrazide), which are protected N-terminal penta-and nona-peptides of the A-chain of bovine insulin respectively. Peptide Ⅰ was prepared from the known tripeptide Ⅲ (N-carbobenzoxy-L-isoleucyl-L-valyl-γ-tert-butyl-L-glutamic acid ethyl ester) through two alternative routes. Peptide Ⅱ was obtained by the hydrazinolysis of peptide Ⅸ (N-carbobenzoxyglycyl-L-isoleucyl-L-valyl-L-glutamyl-L-glutaminyl-S-benzyl-L-cysteinyl-S-benzyl-L-cysteinyl-L-alanyl-O-acetyl-L-serine methyl ester), which was synthesized from peptide Ⅰ by removing the tert-butyl groups and carbo-tert-bytoxyl group with trifluoroacetic acid and coupling with the known tetrapeptide Ⅷ (S-benzyl-L-cysteinyl-S-benzyl-L-cysteinyl-L-alanyl-O-acetyl-L-serine methyl ester hydrobromide) by means of the azide method. The results from elementary analyses, component amino acid determination, paper chromatography and paper electrophoresis indicated that peptides Ⅰ, Ⅱ, Ⅴ, Ⅵ and Ⅸ are chemically pure and homogeneous. The optical purity of these peptides (except Ⅱ and Ⅸ) has been proved by quantitative enzymic hydrolysis by leucine aminopeptidase. Peptide Ⅸ and therefore, peptide Ⅱ are most probably also optically pure L-peptides, because they were prepared from optically pure L-peptides Ⅰ and Ⅷ by the azide method.更多还原