Improved Synthesis of a Macrocyclic Peptide-Like C5aR Antagonist for Intravenous Applications

A multigram scale synthetic procedure for the preparation of a complex and polar macrocyclic peptidic C5aR antagonist is described. The route was developed through improvements to an initial small-scale research synthesis and hinged on optimized solid-phase peptide synthesis featuring an early side...

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Bibliographic Details
Published inOrganic process research & development Vol. 27; no. 11; pp. 2010 - 2019
Main Authors Feng, Yiqing, Liang, Sidney, Langille, Jonathan, Pierce, Betsy S., Chung, Seungwon, Szeliga, Jan, Wilcox, Glenn, Simonds, Paul, Farley, Kathleen A., Li, Bryan, Garcia-Irizarry, Carmen, Jones, Peter, Lira, Ricardo
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 19.10.2023
Subjects
Chemistry
Chemistry, Applied
Chemistry, Organic
Physical Sciences
Science & Technology
HCL
solid-phase peptide synthesis
intravenous applications
RECEPTOR ANTAGONISTS
2-chlorotrityl resin
C5aR antagonist
SOLID-PHASE
peptidomimetic
DEPROTECTION
CLEAVAGE
macro-lactamization
SOLUTION-PHASE SYNTHESIS
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Summary:A multigram scale synthetic procedure for the preparation of a complex and polar macrocyclic peptidic C5aR antagonist is described. The route was developed through improvements to an initial small-scale research synthesis and hinged on optimized solid-phase peptide synthesis featuring an early side chain decoration, a highly efficient off-resin macrolactamization, and global deprotection steps. These improvements resulted in a reduction in off-resin peptide manipulations and ultimately to a 6-fold increase in overall yield from 2-chlorotrityl-bound intermediate SP-7c.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.3c00202