Tagging the Untaggable: A Difluoroalkyl-Sulfinate Ketone-Based Reagent for Direct C-H Functionalization of Bioactive Heteroarenes

Samer Gnaim, Anna Scomparin, Xiuling Li, Phil S. Baran, Christoph Rader, Ronit Satchi-Fainaro, Doron Shabat

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

We have developed a new difluoroalkyl ketal sulfinate salt reagent suitable for direct derivatization of heteroarene C-H bonds. The reagent is capable of introducing a ketone functional group on heteroarene bioactive compounds via a one-pot reaction. Remarkably, in three examples the ketone analog and its parent drug had almost identical cytotoxicity. In a representative example, the ketone analog was bioconjugated with a delivery vehicle via an acid-labile semicarbazone linkage and with a photolabile protecting group to produce the corresponding prodrug. Controlled release of the drug-ketone analog was demonstrated in vitro for both systems. This study provides a general approach to obtain taggable ketone analogs directly from bioactive heteroarene compounds with limited options for conjugation. We anticipate that this sodium ketal-sulfinate reagent will be useful for derivatization of other heteroarene-based drugs to obtain ketone-taggable analogs with retained efficacy.

שפה מקוריתאנגלית
עמודים (מ-עד)1965-1971
מספר עמודים7
כתב עתBioconjugate Chemistry
כרך27
מספר גיליון9
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 21 ספט׳ 2016

ASJC Scopus subject areas

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  • ???subjectarea.asjc.3000.3004???
  • ???subjectarea.asjc.3000.3003???
  • ???subjectarea.asjc.1600.1605???

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