Porter Jacob D, Lindeman Sergey V, Dockendorff Chris
Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, WI, 53201-1881, USA.
Tetrahedron Lett. 2020 Mar 19;61(12). doi: 10.1016/j.tetlet.2020.151654. Epub 2020 Jan 22.
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.
利钠肽受体（NPRs）调节血管钠水平，对于高血压及相关心血管并发症的潜在治疗具有重要意义。肽模拟拮抗剂M372049是研究NPR-C信号传导的一种有价值的探针，遗憾的是目前尚无商业供应。本文描述了一种详细的合成方案，该方案不需要专门的仪器设备，且基于Veale及其同事之前的专利。关键步骤包括碱介导的内酰胺形成和固相支持的肽合成序列。获得了关键内酰胺中间体的X射线晶体结构，以确认该化合物的结构和相对立体化学。
