Rapid approach to complex boronic acids

Sci Adv. 2019 Jul 5;5(7):eaaw4607. doi: 10.1126/sciadv.aaw4607. eCollection 2019 Jul.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boronic Acids / chemical synthesis
  • Boronic Acids / chemistry*
  • Boronic Acids / classification
  • Cyanides / chemical synthesis
  • Cyanides / chemistry
  • Mass Spectrometry / methods
  • Microwaves
  • Molecular Structure*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / classification

Substances

  • Boronic Acids
  • Cyanides
  • Small Molecule Libraries