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Title: Umpolung Ala B Reagents for the Synthesis of Non‐Proteogenic Amino Acids, Peptides and Proteins**
Abstract

Non‐proteogenic amino acids and functionalized peptides are important motifs in modern drug discovery. Here we report that AlaBcan serve as universal building blocks in the synthesis of a diverse collection of modified amino acids, peptides, and proteins. First, we develop the synthesis of AlaBfrom redox‐active esters of aspartic acid resulting in a series of β‐boronoalanine derivatives. Next, we show that AlaBcan be integrated into automated oligopeptide solid‐phase synthesis. AlaBis compatible with common transformations used in preparative peptide chemistry such as native chemical ligation and radical desulfurization as showcased by total synthesis of AlaB‐containing ubiquitin. Furthermore, AlaBreagents participate in Pd‐catalyzed reactions, including C−C cross‐couplings and macrocyclizations. Taken together, AlaBsynthons are practical reagents to access modified peptides, proteins, and in the synthesis of cyclic/stapled peptides.

 
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NSF-PAR ID:
10375474
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Angewandte Chemie
Volume:
134
Issue:
31
ISSN:
0044-8249
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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