Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)-Tronocarpine Enabled by an Asymmetric Michael/Aldol Reaction

Dong-Xing Tan; Jie Zhou; Chao-You Liu; Fu-She Han

doi:10.1002/anie.201914868

Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)-Tronocarpine Enabled by an Asymmetric Michael/Aldol Reaction

Angew Chem Int Ed Engl. 2020 Mar 2;59(10):3834-3839. doi: 10.1002/anie.201914868. Epub 2020 Feb 3.

Authors

Dong-Xing Tan^{1

2}, Jie Zhou^{1

3}, Chao-You Liu¹, Fu-She Han^{1

2}

Affiliations

¹ CAS Key Lab of High-Performance Synthetic Rubber and Its Composite Materials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin, 130022, China.
² University of Science and Technology of China, Hefei, Anhui, 230026, China.
³ The University of Chinese Academy of Sciences, Beijing, 100864, China.

PMID: 31829490
DOI: 10.1002/anie.201914868

Abstract

We present the first asymmetric total synthesis and absolute configuration determination of (+)-tronocarpine. The [6.5.7.6.6] pentacyclic core was constructed at an early stage by using a sequential cyclization strategy through a newly developed catalytic asymmetric Michael/aldol cascade to build the aza[3.3.1]-bridged cycle and a tandem reduction/hemiamidation procedure to assemble the seven-membered lactam. The side-chain functionalities were incorporated at a late stage by several appropriately orchestrated manipulations under mild conditions. The synthesis of enantiomerically pure (+)-tronocarpine was achieved through a 20-step longest linear sequence from tryptamine.

Keywords: configuration determination; indole alkaloids; natural products; organocatalysis; total synthesis.

Publication types

Research Support, Non-U.S. Gov't