德国马克斯-普朗克研究所List, Benjamin团队报道了大麻素和薄荷醇的催化不对称合成。相关研究成果发表在2023年3月1日出版的国际知名学术期刊《自然》。

天然或合成的一般化合物向（1R，6S）-反式异哌啶醇的选择性转化将使薄荷醇和大麻素的可持续路线得以实现并加快。然而，这一反应被认为是不可能的，因为其产物比其原料对所需的酸催化剂更具反应性，从而产生一些副产物。

研究人员表明，一种非对称、强且受限的手性酸，一种高度氟化的亚氨基酰亚胺二磷酸，以优异的效率和选择性催化该过程。将该方法扩展到其他α，β-不饱和醛，可以获得以前不易获得的新大麻素和薄荷醇衍生物。机理研究表明，受限催化剂通过以非反应构象结合产物来完成该反应，从而防止其分解。研究人员还展示了（1R，6S）-反式异哌啶醇如何容易地转化为药学上有用的大麻素和薄荷醇，这两种物质都是迄今为止最短和最具原子经济性的路线。

附：英文原文

Title: Catalytic asymmetric synthesis of cannabinoids and menthol from neral

Author: Grimm, Joyce A. A., Zhou, Hui, Properzi, Roberta, Leutzsch, Markus, Bistoni, Giovanni, Nienhaus, Johanna, List, Benjamin

Issue&Volume: 2023-03-01

Abstract: The selective conversion of natural or synthetic neral to (1R,6S)-trans-isopiperitenol would enable and expedite sustainable routes to menthol1,2 and cannabinoids3,4,5. However, this reaction has been considered impossible because its product is more reactive to the required acid catalysts than its starting material, resulting in several side products6,7,8,9. We now show that an unsymmetric, strong and confined chiral acid, a highly fluorinated imino-imidodiphosphate, catalyses this process with excellent efficiency and selectivity. Expanding the method to other α,β-unsaturated aldehydes could enable access to new cannabinoids and menthol derivatives not readily accessible previously. Mechanistic studies suggest that the confined catalyst accomplishes this reaction by binding the product in an unreactive conformation, thereby preventing its decomposition. We also show how (1R,6S)-trans-isopiperitenol can be readily converted to pharmaceutically useful cannabinoids and menthol, each in the shortest and most atom-economic routes so far.

DOI: 10.1038/s41586-023-05747-9

Source: https://www.nature.com/articles/s41586-023-05747-9