2種のアジド分子を効率的に連結する手法の開発  [in Japanese] Novel Methods for Efficient Conjugation of Two Azide Molecules  [in Japanese]

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Author(s)

    • 吉田 優 Yoshida Suguru
    • 東京医科歯科大学生体材料工学研究所 Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University
    • 喜井 勲 Kii Isao
    • 理化学研究所 ライフサイエンス技術基盤研究センター RIKEN Center for Life Science Technologies
    • 細谷 孝充 Hosoya Takamitsu
    • 東京医科歯科大学生体材料工学研究所|理化学研究所 ライフサイエンス技術基盤研究センター Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University|RIKEN Center for Life Science Technologies

Abstract

"Click reaction", epitomized by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), is an emerging method for conjugating molecules efficiently in broad fields, including materials chemistry and chemical biology. A copper-free variant, strain-promoted azide-alkyne cycloaddition (SPAAC), using functionalized cyclooctyne derivatives that spontaneously react with azides, have enabled the chemical modification of azido-incorporated biomolecules in cultured cells and in living animals, greatly expanding the utility of click chemistry. A variety of cyclooctyne derivatives bearing functional moieties, such as fluorescent or biotinyl groups, have been developed and some of them have become commercially available. However, on-demand synthesis is required for those with a new functionality, which is not always easy because of the high reactivity of the strained alkyne moiety. To conjugate two azide molecules easily, we have developed strain-promoted "double-click" reaction using Sondheimer diyne that bears two strained alkyne moieties. This novel convergent method capable of conjugating three molecules spontaneously has allowed for facile modification of an azido-biomolecule with a small reporter azido-molecule. We have also developed a transient protection method of cyclooctynes from cycloaddition with an azide via 1:1 complexation with a cationic copper(I) salt. Protection of a cyclooctyne bearing a terminal alkyne with a copper salt enabled the selective copper-catalyzed click conjugation with an azide at the terminal alkyne moiety, facilitating easy preparation of cyclooctyne derivatives.

Journal

  • Journal of Synthetic Organic Chemistry, Japan

    Journal of Synthetic Organic Chemistry, Japan 74(5), 453-461, 2016

    The Society of Synthetic Organic Chemistry, Japan

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