Total Synthesis of 4-Azaeudistomin Y1 and Analogues by Inverse-Electron­Demand Diels–Alder Reactions of 3-Aminoindoles with 1,3,5-Triazines

Guoxing Xu; Lianyou Zheng; Qun Dang; Xu Bai

doi:10.1055/s-0032-1316857

Synthesis, Table of Contents

Synthesis 2013; 45(6): 743-752
DOI: 10.1055/s-0032-1316857

paper

Total Synthesis of 4-Azaeudistomin Y₁ and Analogues by Inverse-ElectronDemand Diels–Alder Reactions of 3-Aminoindoles with 1,3,5-Triazines

Guoxing Xu

The Center for Combinatorial Chemistry and Drug Discovery, The School of Pharmaceutical Sciences and The College of Chemistry, Jilin University, Changchun, Jilin 130021, P. R. of China Fax: +86(431)85188955 Email: Qun_dang@merck.com Email: xbai@jlu.edu.cn

,

Lianyou Zheng

The Center for Combinatorial Chemistry and Drug Discovery, The School of Pharmaceutical Sciences and The College of Chemistry, Jilin University, Changchun, Jilin 130021, P. R. of China Fax: +86(431)85188955 Email: Qun_dang@merck.com Email: xbai@jlu.edu.cn

,

Qun Dang*

The Center for Combinatorial Chemistry and Drug Discovery, The School of Pharmaceutical Sciences and The College of Chemistry, Jilin University, Changchun, Jilin 130021, P. R. of China Fax: +86(431)85188955 Email: Qun_dang@merck.com Email: xbai@jlu.edu.cn

,

Xu Bai*

The Center for Combinatorial Chemistry and Drug Discovery, The School of Pharmaceutical Sciences and The College of Chemistry, Jilin University, Changchun, Jilin 130021, P. R. of China Fax: +86(431)85188955 Email: Qun_dang@merck.com Email: xbai@jlu.edu.cn

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Abstract

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Abstract

A new inverse-electron-demand Diels–Alder (IDA) reaction of 3-aminoindoles as dienophiles was developed for the efficient preparation of 4-aza-β-carbolines in high yields. Because N¹-unprotected 3-aminoindoles show poor thermal stability, a one-pot protocol was developed that combines the removal of tert-butoxycarbonyl protecting groups with the IDA reaction. This protocol, using tert-butyl 1H-indol-3-ylcarbamates as reactants, gave the corresponding IDA products in excellent yields. The new IDA methodology was used in a total synthesis of 4-azaeudistomin Y₁, which was obtained in 57% overall yield in four steps. Moreover, the chemistry is suitable for the rapid preparation, through either Friedel–Crafts acylation or amide-formation reactions, of analogues that are useful for exploring structure–activity relationships at the C₁-position.

Key words

indoles - Diels–Alder reactions - heterocycles - total synthesis

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References

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Supplementary Material

Supporting Information

Total Synthesis of 4-Azaeudistomin Y1 and Analogues by Inverse-Electron­Demand Diels–Alder Reactions of 3-Aminoindoles with 1,3,5-Triazines

Total Synthesis of 4-Azaeudistomin Y₁ and Analogues by Inverse-ElectronDemand Diels–Alder Reactions of 3-Aminoindoles with 1,3,5-Triazines