河南师范大学Guo, Hai-Ming研究团队近日取得一项新成果。经过不懈努力,他们研制了通过催化酰基转移亚砜化对映选择性构建立体硫(IV)中心。相关论文于2024年5月8日发表于国际顶尖学术期刊《自然-化学》杂志上。
在这项研究中,课题组开发了一种有效的方法,通过多种亲核试剂(包括芳香胺和醇)的亚砜化,以其双功能手性4-芳基吡啶N-氧化物为催化剂,催化不对称合成手性亚砜酰胺和亚砜酯。这些显著的结果证明了所开发的合成方法的效率、多功能性和广泛的适用性,为硫药效团的合成提供了有价值的工具。
机理实验和密度泛函理论计算表明,该反应的引发和立体控制是由酰基转移催化剂诱导的。他们的研究提供了一种有效的对映选择性构建立体硫(IV)中心的方法。
据悉,手性硫药效团在生物科学和药物化学领域具有重要的应用价值。虽然催化不对称合成亚砜和具有立体基硫(IV)中心的亚硫酸盐酯已经很发达,但手性亚砜酰胺的合成仍然具有挑战性,这主要是由于高亲核性和胺的竞争反应。
附:英文原文
Title: Enantioselective construction of stereogenic-at-sulfur(IV) centres via catalytic acyl transfer sulfinylation
Author: Wei, Tao, Wang, Han-Le, Tian, Yin, Xie, Ming-Sheng, Guo, Hai-Ming
Issue&Volume: 2024-05-08
Abstract: Chiral sulfur pharmacophores are crucial for drug discovery in bioscience and medicinal chemistry. While the catalytic asymmetric synthesis of sulfoxides and sulfinate esters with stereogenic-at-sulfur(IV) centres is well developed, the synthesis of chiral sulfinamides remains challenging, which has primarily been attributed to the high nucleophilicity and competing reactions of amines. In this study, we have developed an efficient methodology for the catalytic asymmetric synthesis of chiral sulfinamides and sulfinate esters by the sulfinylation of diverse nucleophiles, including aromatic amines and alcohols, using our bifunctional chiral 4-arylpyridine N-oxides as catalysts. The remarkable results are a testament to the efficiency, versatility and broad applicability of the developed synthetic approach, serving as a valuable tool for the synthesis of sulfur pharmacophores. Mechanistic experiments and density functional theory calculations revealed that the initiation and stereocontrol of this reaction are induced by an acyl transfer catalyst. Our research provides an efficient approach for the construction of optically pure sulfur(IV) centres.
DOI: 10.1038/s41557-024-01522-z
Source: https://www.nature.com/articles/s41557-024-01522-z
Nature Chemistry:《自然—化学》,创刊于2009年。隶属于施普林格·自然出版集团,最新IF:24.274
官方网址:https://www.nature.com/nchem/
投稿链接:https://mts-nchem.nature.com/cgi-bin/main.plex