Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, P. R. China.
Department of Chemistry, University of Basel, Postfach 3350, Mattenstrasse 24a, 4002, Basel, Switzerland.
Angew Chem Int Ed Engl. 2019 Sep 2;58(36):12688-12695. doi: 10.1002/anie.201906753. Epub 2019 Aug 2.
The synthesis of terpene natural products remains a challenging task due to the enormous structural diversity in this class of compounds. Synthetic catalysts are unable to reproduce the tail-to-head terpene cyclization of cyclase enzymes, which create this diversity from just a few simple linear terpene substrates. Recently, supramolecular structures have emerged as promising enzyme mimetics. In the present study, the hexameric resorcinarene capsule was utilized as an artificial cyclase to catalyze the cyclization of sesquiterpenes. With the cyclization reaction as the key step, the first total synthesis of the sesquiterpene natural product δ-selinene was achieved. This represents the first total synthesis of a sesquiterpene natural product that is based on the cyclization of a linear terpene precursor inside a supramolecular catalyst. To elucidate the reaction mechanism, detailed kinetic studies and kinetic isotope measurements were performed. Surprisingly, the obtained kinetic data indicated that a rate-limiting encapsulation step is operational in the cyclization of sesquiterpenes.
萜类天然产物的合成仍然是一项具有挑战性的任务，因为这类化合物具有巨大的结构多样性。合成催化剂无法复制环化酶中从头至尾的萜类环化反应，而这些酶仅用少数简单的线性萜烯底物就能产生这种多样性。最近，超分子结构已成为有前途的酶模拟物。在本研究中，六聚体间苯二酚胶囊被用作人工环化酶来催化倍半萜的环化反应。以环化反应为关键步骤，首次实现了倍半萜天然产物 δ-蛇麻烯的全合成。这是首次基于线性萜烯前体在超分子催化剂内环化反应的倍半萜天然产物的全合成。为了阐明反应机制，进行了详细的动力学研究和动力学同位素测量。令人惊讶的是，获得的动力学数据表明，在倍半萜的环化反应中存在一个限速的包封步骤。
