Synthesis
DOI: 10.1055/a-1667-3648
short review

Integration of C-Acylation in the Solid-Phase Synthesis of Peptides and Peptidomimetics Employing Meldrum’s Acid, Phosphorus, and Sulfur Ylides

Ahsanullah Ahsanullah
a  Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan
,
Abbas Hassan
a  Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan
,
Farzana L. Ansari
a  Department of Chemistry, Quaid-i-Azam University, 45320 Islamabad, Pakistan
,
b  Institut für Pharmazie, Medizinische Chemie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, 14195 Berlin, Germany
› Author Affiliations
This work was funded by the Deutsche Forschungsgemeinschaft (DFG) and the Higher Education Commission of Pakistan (HEC).


Abstract

The modification of native peptides to peptidomimetics is an important goal in medicinal chemistry and requires, in many cases, the integration of C-acylation steps involving amino acids with classical peptide synthesis. Many classical C-acylation protocols involving Claisen condensations and the use of ylides are not compatible with peptide synthesis, mostly due to the requirements for strong bases leading to epimerization or deprotection of peptides. Meldrum’s acid as well as several specific phosphorus and sulfur ylides, however, are acidic enough to provide reactive C-nucleophiles under mildly basic conditions tolerated during peptide synthesis. This review provides an overview of peptide-compatible C-acylations using Meldrum’s acid and phosphorus and sulfur ylides, and their application in the medicinal chemistry of peptides.

1 Introduction

2 C-Acylation of Meldrum’s Acid

2.1 C-Acylation of Meldrum’s Acid on Solid Phase

3 Ylides as Substrates for C-Acylation

3.1 C-Acylation of Phosphorus Ylides in Solution Phase

3.2 C-Acylation of Solid-Supported Phosphorus Ylides

3.3 C-Acylation of Sulfur Ylides

3.4 C-Acylation of Solid-Supported Sulfur Ylides

4 Miscellaneous Ylides as Acyl Anion Equivalents

5 Summary



Publication History

Received: 22 June 2021

Accepted after revision: 12 October 2021

Publication Date:
12 October 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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