【摘要】 胰岛素B链中段的八肽衍生物,即Cbz·Ser·（Im-Bz）His·Leu·Val·（γ-OCH₃）Glu·Ala·Leu·Tyr·OC₂H5曾自Cbz·Ser·（Im-Bz）His·NHNH₂通过迭氮物与H·Leu·Val·（γ-OCH₃）Glu·Ala·Leu·Tyr·OC₂H₅(B_11-16b)缩合而成。其中B_11-16b由Cbz·Leu·Val·（γ-OCH₃）Glu·Ala·Leu·Tyr·OC₂H₅(B_11-16)经催化氢解或溴化氢醋酸溶液脱去苄氧羰基而得。结晶的B_11-16系从Cbz·Leu·Val·（γ-OCH₃）Glu·OH(B_11-13a)和H·Ala·Leu·Tyr·OC₂H₅借DCCI法缩合而成。从H·（γ-OCH₃）Glu·OH开始,用活化酯法与Cbz·Val·ONP和Cbz·Leu·ONP逐步自N-端引伸,而得Cbz·Val·（γ-OCH₃）Glu·OH(B_12-13a)和Cbz·Leu·Val·（γ-OCH₃）Glu·OH(B_11-13a)。另一八肽衍生物,即Cbz·Ser·（Im-Bz）His·Leu·Val·（γ-OCH₃）Glu·Ala·Leu·Tyr·OH(B_9-16a)系由Cbz·Val·（γ-OCH₃）Glu·Ala·Leu·Tyr·OH(B_12-16a)经催化氢解而得的H·Val·（γ-OCH₃）Glu·Ala·Leu·Tyr·OH借迭氮法与Cbz·Ser·（Im-Bz）His·Leu·N₃缩合而得。该五肽片段B_12-16a又由Cbz·Val·（γ-OCH₃）Glu·ONP与H·Ala·Leu·Tyr·OH缩合而成。更多还原

【Abstract】 Carbobenzoxy-L-seryl-N^im-benzyl-L-histidyl-L-leucyl-L-valyl-γ-methyl-L-glutamyl-L-alanyl-L-leucyl-L-tyrosine (B_9-16a) and its ethyl ester (B_9-16), two derivatives of the octapeptide fragment of the B-chain of insulin, have been synthesized by condensing carbobenzoxy-L-seryl-N^im-benzyl-L-histidyl-L-leucine azide with valyl-γ-methyl-L-glutamyl-L-alanyl-L-leucyl-L-tyrosinate and carbobenzoxy-L-seryl-N^im-benzyl-L-histidine azide with L-leucyl-L-valyl-γ-methyl-L-glutamyl-L-alanyl-L-leucyl-L-tyrosine ethyl ester (B_11-16b)respectively. Carbobenzoxy-L-valyl-γ-methyl-L-glutamic acid(B_12-13a),prepared by coupling ρ-nitrophenyl carbobenzoxyL-valinate with γ-methyl-L-glutamate, was condensed through its ρ-nitrophenyl ester with L-alanyl-L-leucyl-L-tyrosinate to give the protected pentapeptide(B_12-16a).The protected hexapeptide ester(B_11-16) was prepared, through the carbodiimide route,by condensing ethyl-L-alanyl-L-leucyl-L-tyrosinate with carbobenzoxy-L-leucyl-L-valyl-γ-methyl-L-glutamic acid (B_11-13a), which in turn, was obtained by coupling L-valyl-γ-methyl-L-glutamate with ρ-nitrophenyl carbobenzoxy-L-leucinate. The N-free pentapeptide of B_12-16a and the hexapeptide ester (B_11-16b were obtained respectively from B_12-16a and B_11-16 by catalytic hydrogenolysis; whereas, the protected di-and tri-peptide esters (B_9-10 and B_9-11), from which the corresponding hydrazides were obtained, were prepared, through the carbodiimide or the azide route, by condensing carbobenzoxy-L-serine with benzyl N^im-benzyl-L-histidinate and methyl N^im-benzyl-L-histidyl-L-leucinate respectively.更多还原