德国马克斯普朗克研究所Benjamin List课题组报道了以同法尼醇为原料经催化不对称多烯环化制降龙涎醚。相关论文于2024年7月31日发表于国际顶尖学术期刊《自然》杂志上。

该文报道了一种在氟化醇存在下，使用高Bronsted酸性和受限的酰亚胺二磷酰化催化剂，通过催化不对称多烯环化，非对映选择性和对映选择性得到降龙涎醚和倍半萜内酯天然产物(+)-sclareolide的合成方法。包括氘标记研究在内的几个实验表明，该反应主要通过与Stork-Eschenmoser假设一致的途径进行。机理研究表明，酰亚胺二磷酰化催化剂的酶样微环境，对于获得异常高的选择性的重要性，以前认为只有在酶催化的多烯环化中才能实现。

研究人员表示，多烯环化是生物学中最复杂和最具挑战性的转化之一。在一个反应步骤中，多个碳碳键、环体系和立体中心由简单的无环前体构建得到。同时实现这种对产品分布和立体化学的精确控制，对化学家来说是一项艰巨的任务。特别是，(3E,7E)-同法尼醇的多烯环化得到天然存在的有价值的龙涎香气味剂降龙涎醚，被认为是化学合成中的一个长期挑战。

附：英文原文

Title: The catalytic asymmetric polyene cyclization of homofarnesol to ambrox

Author: Luo, Na, Turberg, Mathias, Leutzsch, Markus, Mitschke, Benjamin, Brunen, Sebastian, Wakchaure, Vijay N., Nthling, Nils, Schelwies, Mathias, Pelzer, Ralf, List, Benjamin

Issue&Volume: 2024-07-31

Abstract: Polyene cyclizations are among the most complex and challenging transformations in biology. In a single reaction step, multiple carbon–carbon bonds, ring systems and stereogenic centres are constituted from simple, acyclic precursors. Simultaneously achieving this kind of precise control over product distribution and stereochemistry poses a formidable task for chemists. In particular, the polyene cyclization of (3E,7E)-homofarnesol to the valuable naturally occurring ambergris odorant ()-ambrox is recognized as a longstanding challenge in chemical synthesis. Here we report a diastereoselective and enantioselective synthesis of ()-ambrox and the sesquiterpene lactone natural product (+)-sclareolide by a catalytic asymmetric polyene cyclization by using a highly Brnsted-acidic and confined imidodiphosphorimidate catalyst in the presence of fluorinated alcohols. Several experiments, including deuterium-labelling studies, suggest that the reaction predominantly proceeds through a concerted pathway in line with the Stork–Eschenmoser hypothesis. Mechanistic studies show the importance of the enzyme-like microenvironment of the imidodiphosphorimidate catalyst for attaining exceptionally high selectivities, previously thought to be achievable only in enzyme-catalysed polyene cyclizations.

DOI: 10.1038/s41586-024-07757-7

Source: https://www.nature.com/articles/s41586-024-07757-7