Tunable Site Selectivity and Chemo- and Regioselectivity: Diversification of Indole Alkaloid Privileged Scaffolds Enabled by λ<sup>3</sup>-Iodane-Mediated Cross-Nucleophile Coupling Cascade

Amidst nature's repertoire of small molecule architectures, indole alkaloid-derived privileged scaffolds continuously support innovation in bioactive compound discovery and propel fragment-based drug design. Herein, we realized a metal-free, site-selective, and chemo- and regioselective cross-nucleophile coupling cascade of pluripotent indole-enamine-aniline intermediates by use of λ<sup>3</sup>-iodane-mediated umpolung chemistry. The protocol is applicable toward the divergent synthesis of valuable benzo[<i>c</i>]indolo[3,2-<i>j</i>][2,6]naphthyridines and azepino[4,5-<i>b</i>]indoles, which are very important privileged scaffolds in communesin-, peroforamidine-, and iboga-type alkaloids. The control experiments and theoretical calculations provide insights into the reaction mechanism and the site-selectivity of umpolung induced by λ<sup>3</sup>-iodane.

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Publication Details

Journal
Organic Letters
Published
2025-09-01
DOI
https://doi.org/10.1021/acs.orglett.5c03224
Citations
1
Primary Topic
Alkaloids: synthesis and pharmacology
Type
article
Field-Weighted Citation Impact
1.56

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article

Tunable Site Selectivity and Chemo- and Regioselectivity: Diversification of Indole Alkaloid Privileged Scaffolds Enabled by λ3-Iodane-Mediated Cross-Nucleophile Coupling Cascade

Kaitong Zhuang, Yan Fu, Xiaopeng Qiu, Lei Wang et al.
1 citations
Organic Letters
Alkaloids: synthesis and pharmacology
1.56
article

Tunable Site Selectivity and Chemo- and Regioselectivity: Diversification of Indole Alkaloid Privileged Scaffolds Enabled by λ3-Iodane-Mediated Cross-Nucleophile Coupling Cascade

Kaitong Zhuang, Yan Fu, Xiaopeng Qiu, Lei Wang, Zenghui Sun, Shaoguang Sun, Ran Guo, Zixin Jin, Yujia Bai, Ruijuan Xing, ziyi zhang, Shiyang Xin, Yi Liu, Haochen Zhang, Lu Yang
article en
1 citations

Abstract

Amidst nature's repertoire of small molecule architectures, indole alkaloid-derived privileged scaffolds continuously support innovation in bioactive compound discovery and propel fragment-based drug design. Herein, we realized a metal-free, site-selective, and chemo- and regioselective cross-nucleophile coupling cascade of pluripotent indole-enamine-aniline intermediates by use of λ<sup>3</sup>-iodane-mediated umpolung chemistry. The protocol is applicable toward the divergent synthesis of valuable benzo[<i>c</i>]indolo[3,2-<i>j</i>][2,6]naphthyridines and azepino[4,5-<i>b</i>]indoles, which are very important privileged scaffolds in communesin-, peroforamidine-, and iboga-type alkaloids. The control experiments and theoretical calculations provide insights into the reaction mechanism and the site-selectivity of umpolung induced by λ<sup>3</sup>-iodane.

Organic LettersVol. 27(36)
Shenyang Pharmaceutical University (CN), Hebei Medical University (CN), Ministry of Education of the People's Republic of China (CN), Pharmaron (United Kingdom) (GB), Shijiazhuang Yiling Pharmaceutical (China) (CN)
Hebei Provincial Department of Human Resources and Social Security, National Natural Science Foundation of China, Department of Education of Hebei Province, Natural Science Foundation of Hebei Province, Hebei Medical University
Openalex Percentile: Top 16%
Alkaloids: synthesis and pharmacology
1.56
DOISourceOpenAlex
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