Department of Chemistry, University of Colorado, Boulder, Colorado 80309, United States.
Org Lett. 2024 Apr 5;26(13):2590-2595. doi: 10.1021/acs.orglett.4c00609. Epub 2024 Mar 22.
In this Letter, we report a direct and robust desulfurization method employing water-soluble phosphine, specifically tris(2-carboxyethyl)phosphine hydrochloride (TCEP), and tetrahydroxydiboron (B(OH)), which serves as a radical initiator. This innovative reaction exhibits compatibility with a diverse array of substrates, including cysteine residues in chemically synthesized oligopeptides and cyclic peptides, alkyl thiols in bioactive molecules, disulfides in commercial proteins, and selenocysteine. We optimized the reaction conditions to minimize the formation of undesired oxidized and borylated byproducts. Furthermore, the refined desulfurization process is executed after native chemical ligation (NCL) in a single pot, streamlining the existing synthetic approaches. This demonstrates its potential applications in the synthesis of complex peptides and proteins, showcasing a significant advancement in the field.
在这封信件中，我们报告了一种采用水溶性膦，特别是三（2-羧乙基）膦盐酸盐（TCEP）和四羟二硼（B（OH））作为自由基引发剂的直接且有效的脱硫方法。这种创新的反应与各种底物兼容，包括化学合成的寡肽和环肽中的半胱氨酸残基、生物活性分子中的烷基硫醇、商业蛋白质中的二硫键以及硒代半胱氨酸。我们优化了反应条件，以最小化不期望的氧化和硼化副产物的形成。此外，在单个容器中进行天然化学连接（NCL）后进行精制脱硫，简化了现有的合成方法。这表明它在复杂肽和蛋白质的合成中有潜在的应用，在该领域取得了重大进展。
