Solution-phase submonomer diversification of aza-dipeptide building blocks and their application in aza-peptide and aza-DKP synthesis.
Aza-peptides have been used as tools for studying SARs in programs aimed at drug discovery and chemical biology. Protected aza-dipeptides were synthesized by a solution-phase submonomer approach featuring alkylation of N-terminal benzophenone semicarbazone aza-Gly-Xaa dipeptides using different alkyl halides in the presence of potassium tert-butoxide as base. Benzophenone protected aza-dipeptide tert-butyl ester 31c was selectively deprotected at the C-terminal ester or N-terminal hydrazone to afford, respectively, aza-dipeptide acid and amine building blocks 36c and 40c, which were introduced into longer aza-peptides. Alternatively, removal of the benzophenone semicarbazone protection from aza-dipeptide methyl esters 29a-c led to intramolecular cyclization to produce aza-DKPs 39a-c. In light of the importance of aza-peptides and DKPs as therapeutic agents and probes of biological processes, this diversity-oriented solution-phase approach may provide useful tools for studying peptide science.
Bourguet
Carine B
CB
Département de Chimie, Université de Montréal, Montréal, Québec, Canada.
Proulx
Caroline
C
Klocek
Sophie
S
Sabatino
David
D
Lubell
William D
WD
D000595:Amino Acid Sequence; D001577:Benzophenones / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry; D006834:Hydrazines / Q000737:chemistry; D015394:Molecular Structure; D012664:Semicarbazones / Q000737:chemistry
D001577:Benzophenones; D002273:Carcinogens; D004151:Dipeptides; D006834:Hydrazines; D012664:Semicarbazones; C029424:hydrazine; C047723:benzophenone