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Sesquiterpene Cyclizations inside the Hexameric Resorcinarene Capsule: Total Synthesis of δ‐Selinene and Mechanistic Studies
Author(s) -
Zhang Qi,
Tiefenbacher Konrad
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201906753
Subject(s) - chemistry , sesquiterpene , terpene , resorcinarene , biocatalysis , stereochemistry , supramolecular chemistry , catalysis , natural product , organic chemistry , combinatorial chemistry , reaction mechanism , molecule
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.