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. 2020 Mar 19;61(12):151654.
doi: 10.1016/j.tetlet.2020.151654. Epub 2020 Jan 22.

Modified Synthesis of the Peptidomimetic Natriuretic Peptide Receptor-C Antagonist M372049

Jacob D Porter  1 , Sergey V Lindeman  1 , Chris Dockendorff  1
Affiliations

Modified Synthesis of the Peptidomimetic Natriuretic Peptide Receptor-C Antagonist M372049

Jacob D Porter et al. Tetrahedron Lett. .

Abstract

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.

Keywords: M372049; NPR-C antagonist; Natriuretic Peptide Receptor-C; lactam; peptide synthesis; peptidomimetic.

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Figures

Figure 1.
Figure 1.
Retrosynthesis of M372049 (1).
Figure 2.
Figure 2.
X-ray structure of lactam 12
Scheme 1.
Scheme 1.
Synthesis of western quinoxaline-amide-acid 2
Scheme 2.
Scheme 2.
Synthesis of γ-lactam 3
Scheme 3.
Scheme 3.
Assembly of M372049 via SPPS
See this image and copyright information in PMC

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