Asymmetric Total Synthesis of Hetidine-Type C<sub>20</sub>-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine
Quan-Zheng Zhang, Zhao Yang, Qi Wang, Shuangwei Liu, Tao Zhou, Yankun Zhao, Min Zhang
Abstract
Here, we report the first asymmetric total synthesis of (+)-talassimidine and (+)-talassamine, two hetidine-type C20-diterpenoid alkaloids. A highly regio- and diastereoselective 1,3-dipolar cycloaddition of an azomethine ylide yielded a chiral tetracyclic intermediate in high enantiopurity, thus providing the structural basis for asymmetric assembly of the hexacyclic hetidine skeleton. In this key step, the introduction of a single chiral center induces four new continuous chiral centers. Another key transformation is the dearomative cyclopropanation of the benzene ring and subsequent SN2-like ring opening of the resultant cyclopropane ring with water as a nucleophile, which not only establishes the B ring but also precisely installs the difficult-to-achieve equatorial C7–OH group.