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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Published in | Organic process research & development Vol. 27; no. 11; pp. 2010 - 2019 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
Amer Chemical Soc
19.10.2023
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Subjects | |
Online Access | Get full text |
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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. |
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ISSN: | 1083-6160 1520-586X |
DOI: | 10.1021/acs.oprd.3c00202 |