Synthesis of bis-amino acid derivatives by Suzuki cross-coupling, Michael addition and substitution reactions.
Several bis-amino acids were prepared using a bis-Suzuki coupling (compounds 4-8, 10), a sequential Michael addition and bis-Suzuki coupling (compounds 12, 13) and a Michael addition followed by a substitution reaction (compounds 18, 19). Thus, the pure stereoisomer of the methyl esters of N-(tert-butoxycarbonyl)-beta-bromodehydroaminobutyric acid and dehydrophenylalanine and of N-benzyloxycarbonyl-beta-bromodehydroaminobutyric acid were reacted with 1,4-phenylene-bis-boronic acid or 9,9-dioctyl-9H-fluorene-2,7-bis-boronic acid using modified Suzuki coupling conditions. The corresponding bis-dehydroamino acid derivatives were obtained in good to high yields maintaining the stereochemistry of the starting materials. This reaction was also applied successfully to a brominated dehydrodipeptide and 1,4-phenylene-bis-boronic acid showing that it could be used to create cross-links in peptide chains. An N,N-diacyldehydroalanine derivative was used in a sequential Michael addition and bis-Suzuki coupling giving a p-terphenyl bis-amino acid and a fluorenyl bis-amino acid in good yields. Two bis-alpha,beta-diamino acids were obtained by a Michael addition of 1,2,4-triazole to the methyl esters of N-(4-toluenesulfonyl), N-(tert-butoxycarbonyl) dehydroamino acids followed by treatment with ethylenediamine.
Ferreira
P M T
PM
Department of Chemistry, University of Minho, Gualtar 4710-057, Braga, Portugal. pmf@quimica.uminho.pt
Monteiro
L S
LS
Queiroz
M-J R P
MJ
Pereira
G
G
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D003432:Cross-Linking Reagents; D005029:Ethylenediamines; D010455:Peptides; C031234:ethylenediamine