硫酸酯的全固相合成及结构解析

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2025-04-05 DOI:10.1016/j.tet.2025.134650

Ajit Hanumant Chandgude , Ravinder Reddy Patlolla , Jayvant Harlikar , Linga Banoth

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引用次数: 0

摘要

Sovateltide （IRL-1620, PMZ-1620）是一种人工合成的内皮素-1类似物，是一种很有前景的急性缺血性脑卒中治疗剂。本研究详细介绍了Sovateltide的全固相肽合成（SPPS）及其随后的结构解析。SPPS依赖于脱保护、偶联和在固体载体上洗涤14个氨基酸肽链的重复循环。在树脂裂解和侧链官能团去保护后，使用制备型高效液相色谱（Prep HPLC）纯化Sovateltide至均匀性。在13.8 mmol尺度下，Sovateltide成功合成和纯化，总产率为~ 28%，产品纯度≥98%。采用质谱、核磁共振和CD谱分析进行结构确认。LCMS分析证实了氨基酸序列，2D NMR数据证实了其结构。通过CD谱分析证实了二级结构的估计。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Total solid-phase synthesis and structural elucidation of sovateltide

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Total solid-phase synthesis and structural elucidation of sovateltide

Sovateltide (IRL-1620, PMZ-1620), a synthetic endothelin-1 analog, is a promising therapeutic agent for acute ischemic stroke. This study details the total solid-phase Peptide synthesis (SPPS) of Sovateltide and its subsequent structural elucidation. SPPS relies on the repetitive cycles of deprotection, coupling, and washing the 14-amino acid peptide chain on a solid support. Following cleavage from the resin and deprotection of side chain functionalities, Sovateltide was purified to homogeneity using preparative high-performance liquid chromatography (Prep HPLC). The Sovateltide successful synthesis and purification was achieved with overall yields∼28 % and product purity of ≥98 % at 13.8 mmol scale. Structural confirmation was achieved using mass spectrometry, NMR, and CD spectroscopy analysis. LCMS analysis confirmed the amino acid sequence, while 2D NMR data validated its structure. The secondary structure estimation was confirmed through CD spectroscopy.

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.