The Natriuretic Peptide Receptors (NPRs) regulate vascular sodium levels and have been of significant interest for the potential treatment of hypertension and related cardiovascular complications. The peptidomimetic antagonist M372049 is a valuable probe for the study of NPR-C signaling, unfortunately it is presently not commercially available. Described is a detailed protocol for its synthesis that does not require specialized apparatus and builds upon a prior patent from Veale and colleagues. Key steps include a base-mediated lactam formation and a solid-supported peptide synthetic sequence. An X-ray crystal structure of a key lactam intermediate was obtained to confirm the structure and relative stereochemistry of the compound.
Porter, Jacob; Lindeman, Sergey V.; and Dockendorff, Chris, "Modified Synthesis of the Peptidomimetic Natriuretic Peptide Receptor-C Antagonist M372049" (2020). Chemistry Faculty Research and Publications. 1005.
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Accepted version. Tetrahedron Letters, Vol. 61, No. 12 (March 19, 2020): 151654. DOI. © 2020 Elsevier. Used with permission.