A Modular Approach for Diversity-Oriented Synthesis of 1,3-trans-Disubstituted Tetrahydroisoquinolines: Seven-Step Asymmetric Synthesis of Michellamines B and C

Miao Bai; Shihu Jia; Jingyang Zhang; Hong-Gang Cheng; Hengjiang Cong; Shanshan Liu; Zhiqian Huang; Yaoguo Huang; Xiaoming Chen; Qianghui Zhou

doi:10.1002/anie.202205245

A Modular Approach for Diversity-Oriented Synthesis of 1,3-trans-Disubstituted Tetrahydroisoquinolines: Seven-Step Asymmetric Synthesis of Michellamines B and C

Angew Chem Int Ed Engl. 2022 Aug 1;61(31):e202205245. doi: 10.1002/anie.202205245. Epub 2022 Jun 17.

Authors

Affiliations

¹ Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, and The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.
² Daicel Chiral Technologies (China) Co., Ltd., Shanghai, 200131, China.
³ State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Rd, Shanghai, 200032, China.

PMID: 35616270
DOI: 10.1002/anie.202205245

Abstract

1,3-trans-Disubstituted tetrahydroisoquinoline (THIQ) is a common heterocyclic structural unit of naphthylisoquinoline alkaloids. The assembly of this structural unit is not trivial, which constitutes a substantial challenge in the total synthesis of naphthylisoquinoline alkaloids and related pharmaceuticals. Herein, we report a modular and convergent method for the rapid assembly of 1,3-trans-disubstituted THIQ frameworks through a three-component Catellani reaction and a Au^I -catalyzed cyclization/reduction cascade. With widely available simple aryl iodides, aziridines and (triisopropylsilyl)acetylene as the building blocks, this method paves a practical way for the diversity-oriented synthesis of 1,3-trans-disubstituted THIQs. Based on this new method, concise syntheses of an analogue of the new drug mevidalen and four naphthylisoquinoline alkaloids have been accomplished, demonstrating the broad synthetic utility of this approach.

Keywords: Diversity-Oriented Synthesis; Heterocycles; Naphthylisoquinoline Alkaloids; Tetrahydroisoquinolines; Total Synthesis.

Publication types

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

MeSH terms

Alkaloids* / chemistry
Cyclization
Iodides
Molecular Structure
Stereoisomerism
Tetrahydroisoquinolines* / chemistry

Substances

Alkaloids
Iodides
Tetrahydroisoquinolines