Synthesis of the Mitogenic S-[2,3-Bis(palmitoyloxy)propyl]-N-palmitoylpentapeptide fromEscherichia coliLipoprotein

Abstract

The N-terminal pentapeptide of the lipoprotein from the outer membrane of E. coli was obtained by coupling S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-N-palmitoyl-(R)-cysteine to O-tert-butylseryl-O-tert-butylseryl-asparaginyl-alanine tert-butyl ester, followed by deprotection with trifluoroacetic acid. The tetrapeptide was built up from alanine tert-butyl ester with N-9-fluorenylmethyloxycarbonyl protected amino acids. S-[2,3-Bis(palmitoyloxy)-propyl]-N-palmitoylcysteine was obtained from N,N''-dipalmitoylcystine di-tert-butyl ester via reduction to the thiol and S-alkylation with racemic 3-bromo-1,2-propanediol, followed by esterification with palmitic acid in the presence of dicyclohexylcarbodiimide/dimethylaminopyridine and deprotection with trifluoroacetic acid. The compounds were characterized unequivocally by 13C-NMR and mass spectra. The diastereomers of S-[2,3-bis(palmitoyloxy)propyl]-N-palmitoylcysteine tert-butyl ester with opposite configuration at the propyl-C-2 atom could be separated on a silica gel column.