Rapid approach to complex boronic acids

Constantinos G Neochoritis, Shabnam Shaabani, Maryam Ahmadianmoghaddam, Tryfon Zarganes-Tzitzikas, Li Gao, Michaela Novotná, Tatiana Mitríková, Atilio Reyes Romero, Marina Ika Irianti, Ruixue Xu, Joe Olechno, Richard Ellson, Victoria Helan, Michael Kossenjans, Matthew R Groves, Alexander Dömling*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)
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Abstract

The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing-enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries.

Original languageEnglish
Article numbereaaw4607
Number of pages9
JournalScience Advances
Volume5
Issue number7
DOIs
Publication statusPublished - 3-Jul-2019

Keywords

  • PROTEIN-TYROSINE-PHOSPHATASE
  • CROSS-COUPLING REACTIONS
  • MULTICOMPONENT REACTIONS
  • ISOCYANIDE SYNTHESIS
  • CHEMISTRY
  • PREDICTION
  • INHIBITORS
  • PYRAZINES
  • REAGENTS
  • STATE

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