Solution-phase submonomer diversification of aza-dipeptide building blocks and their application in aza-peptide and aza-DKP synthesis
✍ Scribed by Carine B. Bourguet; Caroline Proulx; Sophie Klocek; David Sabatino; Prof. William D. Lubell
- Book ID
- 105359865
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 422 KB
- Volume
- 16
- Category
- Article
- ISSN
- 1075-2617
- DOI
- 10.1002/psc.1235
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✦ Synopsis
Abstract
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. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.