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

Ethyl 2-benzoyl-3-dimethylaminopropenoate (6) and methyl 2-benzoylamin o-3-dimethylaminopropenoate (46) were used as reagents for the protect ion of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-be nzoylamino-2-methoxycarbonylvinyl groups in the peptide synthesis. Rea ctions of ethyl 2-benzoyl-3-dimethylaminopropenoate (6) with alpha-ami no 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 achieve d by hydrazine monohydrochloride or hydroxylamine hydrochloride, affor ded 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-me thoxycarbonylvinyl-1)glycine (47), which was coupled with glycine ethy l ester to give nzoylamino-2-methoxycarbonylvinyl-1)glycyl]glycine eth yl ester (48). Treatment of 48 with 2-amino-4,6-dimethylpyrimidine aff orded N-[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparatio n of tri- 58-70, tetra- 71-82, and pentapeptide esters 83-85 containin g N-terminal 3-heteroarylamino-2,3-dehydroalanine. 2-Chloro-4,6-dimeth oxy-1,3,5-triazine was employed as a coupling reagent for the preparat ion of peptides 58-85.