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Bioorthogonal release of sulfonamides and mutually orthogonal liberation of two drugs.

ABSTRACT: Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M-1 s-1, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine-DIBAC and benzonorbornadiene-tetrazine cycloaddition pairs, which can be used for selective and simultaneous liberation of sulfonamide and primary amine drugs.

SUBMITTER: Shao Z

PROVIDER: S-EPMC6314811 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Bioorthogonal release of sulfonamides and mutually orthogonal liberation of two drugs.

Shao Zhuzhou Z Liu Wei W Tao Huimin H Liu Fang F Zeng Ruxin R Champagne Pier Alexandre PA Cao Yang Y Houk K N KN Liang Yong Y

Chemical communications (Cambridge, England) 20181201 100

Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M-1 s-1, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine-DIBAC and benzonorbornadiene-t ...[more]

PMID: 30480281

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