Catalytic enantioselective nitrone cycloadditions enabling collective syntheses of indole alkaloids

Xiaochen Tian; Tengfei Xuan; Jingkun Gao; Xinyu Zhang; Tao Liu; Fengbiao Luo; Ruochen Pang; Pengcheng Shao; Yun-Fang Yang; Yang Wang

doi:10.1038/s41467-024-50509-4

Catalytic enantioselective nitrone cycloadditions enabling collective syntheses of indole alkaloids

Nat Commun. 2024 Jul 31;15(1):6429. doi: 10.1038/s41467-024-50509-4.

Authors

Xiaochen Tian^#^{1

2}, Tengfei Xuan^#^{1

2}, Jingkun Gao^#³, Xinyu Zhang¹, Tao Liu¹, Fengbiao Luo¹, Ruochen Pang¹, Pengcheng Shao¹, Yun-Fang Yang⁴, Yang Wang^{5

6}

Affiliations

¹ Molecular Synthesis Center & Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
² Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, China.
³ State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key Laboratory of Green Chemistry-Synthesis Technology of Zhejiang Province, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
⁴ State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key Laboratory of Green Chemistry-Synthesis Technology of Zhejiang Province, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China. [email protected].
⁵ Molecular Synthesis Center & Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China. [email protected].
⁶ Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, China. [email protected].

^# Contributed equally.

Abstract

Tetrahydro-β-carboline skeletons are prominent and ubiquitous in an extraordinary range of indole alkaloid natural products and pharmaceutical compounds. Powerful synthetic approaches for stereoselective synthesis of tetrahydro-β-carboline skeletons have immense impacts and have attracted enormous attention. Here, we outline a general chiral phosphoric acid catalyzed asymmetric 1,3-dipolar cycloaddition of 3,4-dihydro-β-carboline-2-oxide type nitrone that enables access to three types of chiral tetrahydro-β-carbolines bearing continuous multi-chiral centers and quaternary chiral centers. The method displays different endo/exo selectivity from traditional nitrone chemistry. The distinct power of this strategy has been illustrated by application to collective and enantiodivergent total syntheses of 40 tetrahydro-β-carboline-type indole alkaloid natural products with divergent stereochemistry and varied architectures.

Abstract

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