Catalytic Enantioselective α‐Ethynylation of Oxindoles: Total Synthesis of (‐)‐Corynoxine, (‐)‐Isorhynchophylline, (‐)‐Aspidospermidine, and (‐)‐Limaspermidine

B Bao‐Kuan Guo (School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China) Y Yu‐Dong Zhang (State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China) J Ju‐Song Yang (State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China) J Jin‐Rui Tian (State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China) X Xiao‐Ming Zhang (State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China) F Fu‐Min Zhang (State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China) Y Yong‐Qiang Tu (School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China)

Abstract

Abstract The all‐carbon quaternary stereogenic center of oxindoles is a crucial structural element of a broad spectrum of indole alkaloids, imparting these molecules with rigid three‐dimensional configurations essential for their biological activities. Here, we present a catalytic asymmetric α‐ethynylation reaction of oxindoles taking advantage of the catalysis of a spiropyrrolidine amide (SPA) triazolium. This transformation enables the enantioselective construction of the C3 quaternary carbon stereocenter of oxindoles while introducing a versatile ethynyl functionality. Employment of this methodology has been demonstrated in the divergent total synthesis of indole alkaloids (‐)‐corynoxine, (‐)‐isorhynchophylline, (‐)‐aspidospermidine, and (‐)‐limaspermidine, featuring a protecting group‐dependent 1,6‐Michael addition or an aminolysis/1,6‐Michael addition sequence to generate two distinct types of spiro‐indoles, tailored for different late‐stage synthetic purposes.

Article Details

Volume / Issue Vol. 64, Issue 26
Published June 24, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (7)

B

Bao‐Kuan Guo

School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China

Y

Yu‐Dong Zhang

State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China

J

Ju‐Song Yang

State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China

J

Jin‐Rui Tian

State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China

X

Xiao‐Ming Zhang

State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China

F

Fu‐Min Zhang

State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University Lanzhou 730000 China

Y

Yong‐Qiang Tu

School of Pharmaceutical Sciences School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs State Key Laboratory of Synergistic Chem‐Bio Synthesis Shanghai Jiao Tong University Shanghai China