2-BENZOYL-2-ETHOXYCARBONYLVINYL-1 AND 2-BENZOYLAMINO-2-METHOXYCARBONYLVINYL-1 AS N-PROTECTING GROUPS IN PEPTIDE SYNTHESIS - THEIR APPLICATION IN THE SYNTHESIS OF DEHYDROPEPTIDE DERIVATIVES CONTAINING N-TERMINAL-3-HETEROARYLAMINO-2,3-DEHYDROALANINE

摘要

Ethyl 2-benzoyl-3-dimethylaminopropenoate (6) and methyl 2-benzoylamino-3-dimethylaminopropenoate (46) were used as reagents for the protection of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2-benzoyl-3-dimethylaminopropenoate (6) with alpha-amino acids gave N-(2-benzoyl-2-ethoxycarbonylvinyl-1)-alpha-amino acids 13-19. These were coupled with various amino acid esters to form N-(2-benzoyl-2-ethoxycarbonylvinyl-1)-protected dipeptide esters 20-31. The removal of 2-benzoyl-2-ethoxycarbonylvinyl-1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlorides of dipeptide esters 32-41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2-benzoylamino-3-dimethylaminopropenoate (46) by glycine gave N-(2-benzoylamino-2-methoxycarbonylvinyl-1)glycine (47), which was coupled with glycine ethyl ester to give N-[N-(2-benzoylamino-2-methoxycarbonylvinyl-1)glycyl]glycine ethyl ester (48). Treatment of 48 with 2-amino-4,6-dimethylpyrimidine afforded N-[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri- 58-70, tetra- 71-82, and pentapeptide esters 83-85 containing N-terminal 3-heteroarylamino-2,3-dehydroalanine. 2-Chloro-4,6-dimethoxy-1,3,5-triazine was employed as a coupling reagent for the preparation of peptides 58-85. [References: 16]