Premium
2‐Benzoyl‐2‐ethoxycarbonylvinyl‐1 and 2‐benzoylamino‐2‐methoxy‐carbonylvinyl‐1 as N ‐protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N ‐terminal 3‐heteroarylamino‐2,3‐dehydroalanine
Author(s) -
Svete Jurij,
AljažRožič Mateja,
Stanovnik Branko
Publication year - 1997
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570340128
Subject(s) - chemistry , dipeptide , glycine , hydrochloride , reagent , yield (engineering) , amino acid , peptide synthesis , ethyl ester , peptide , pentapeptide repeat , organic chemistry , medicinal chemistry , stereochemistry , biochemistry , metallurgy , materials science
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 α‐amino acids gave N ‐(2‐benzoyl‐2‐ethoxycarbonylvinyl‐1)‐α‐amino acids 13–19. These were coupled with various amino acid esters to form N ‐(2‐benzoyl‐2‐ethoxycar‐bonylvinyl‐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 hydrochlo‐rides 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‐methoxycar‐bonylvinyl‐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‐arnino‐4,6‐dirnethylpyrimi‐dine 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.