Water-Compatible Staudinger-Diels-Alder Ligation

Masaru Tanioka; Shohei Kanayama; Fumino Kitamura; Akinari Takano; Yukiko Ikeda; Aki Kohyama; Tsuyoshi Yamada; Yuji Matsuya

doi:10.1021/acs.joc.4c02306

Water-Compatible Staudinger-Diels-Alder Ligation

Masaru Tanioka^*, Shohei Kanayama, Fumino Kitamura, Akinari Takano, Yukiko Ikeda, Aki Kohyama, Tsuyoshi Yamada, Yuji Matsuya^*

^*Corresponding author for this work

Synthetic and Medicinal Chemistry

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

The development of bioorthogonal reactions is expected to propel further advances in chemical biology. In this study, we demonstrate Staudinger-Diels-Alder (SDA) ligation as a candidate for a new bioorthogonal reaction. This reaction ligates two molecules via strong C-C bonds at room temperature. We found that the aryl substituent of azide-benzocyclobutene (azide-BCB) had a strong influence on the molecule’s tolerance to water. In particular, Cl-substituted azide-BCBs generated the ligated product in high yield, even in the presence of water. Mechanistic investigations using DFT methods revealed that hydrophobic electron-withdrawing substituents suppressed the side reactions of SDA ligation.

Original language	English
Pages (from-to)	1501-1506
Number of pages	6
Journal	Journal of Organic Chemistry
Volume	90
Issue number	4
DOIs	https://doi.org/10.1021/acs.joc.4c02306
State	Published - 2025/01/31

ASJC Scopus subject areas

Organic Chemistry

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title = "Water-Compatible Staudinger-Diels-Alder Ligation",

abstract = "The development of bioorthogonal reactions is expected to propel further advances in chemical biology. In this study, we demonstrate Staudinger-Diels-Alder (SDA) ligation as a candidate for a new bioorthogonal reaction. This reaction ligates two molecules via strong C-C bonds at room temperature. We found that the aryl substituent of azide-benzocyclobutene (azide-BCB) had a strong influence on the molecule{\textquoteright}s tolerance to water. In particular, Cl-substituted azide-BCBs generated the ligated product in high yield, even in the presence of water. Mechanistic investigations using DFT methods revealed that hydrophobic electron-withdrawing substituents suppressed the side reactions of SDA ligation.",

author = "Masaru Tanioka and Shohei Kanayama and Fumino Kitamura and Akinari Takano and Yukiko Ikeda and Aki Kohyama and Tsuyoshi Yamada and Yuji Matsuya",

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doi = "10.1021/acs.joc.4c02306",

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T1 - Water-Compatible Staudinger-Diels-Alder Ligation

AU - Tanioka, Masaru

AU - Kanayama, Shohei

AU - Kitamura, Fumino

AU - Takano, Akinari

AU - Ikeda, Yukiko

AU - Kohyama, Aki

AU - Yamada, Tsuyoshi

AU - Matsuya, Yuji

PY - 2025/1/31

Y1 - 2025/1/31

N2 - The development of bioorthogonal reactions is expected to propel further advances in chemical biology. In this study, we demonstrate Staudinger-Diels-Alder (SDA) ligation as a candidate for a new bioorthogonal reaction. This reaction ligates two molecules via strong C-C bonds at room temperature. We found that the aryl substituent of azide-benzocyclobutene (azide-BCB) had a strong influence on the molecule’s tolerance to water. In particular, Cl-substituted azide-BCBs generated the ligated product in high yield, even in the presence of water. Mechanistic investigations using DFT methods revealed that hydrophobic electron-withdrawing substituents suppressed the side reactions of SDA ligation.

AB - The development of bioorthogonal reactions is expected to propel further advances in chemical biology. In this study, we demonstrate Staudinger-Diels-Alder (SDA) ligation as a candidate for a new bioorthogonal reaction. This reaction ligates two molecules via strong C-C bonds at room temperature. We found that the aryl substituent of azide-benzocyclobutene (azide-BCB) had a strong influence on the molecule’s tolerance to water. In particular, Cl-substituted azide-BCBs generated the ligated product in high yield, even in the presence of water. Mechanistic investigations using DFT methods revealed that hydrophobic electron-withdrawing substituents suppressed the side reactions of SDA ligation.

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DO - 10.1021/acs.joc.4c02306

M3 - 学術論文

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JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 4

ER -

Water-Compatible Staudinger-Diels-Alder Ligation

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