An Alkylsilyl-Tethered, High-Capacity Solid Support Amenable to Diversity-Oriented Synthesis for One-Bead, One-Stock Solution Chemical Genetics

JA Tallarico, KM Depew, HE Pelish, Nicholas James Westwood, CW Lindsley, MD Shair, SL Schreiber, MA Foley

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

The synthesis and use of an alkylsilyl-tethered large (500-600 mum) polystyrene resin (1) are disclosed. An optimized Suzuki coupling of bromine-functionalized polystyrene and a silicon-functionalized alkylborane generates the silicon-substituted polystyrene 1 in large scale (> 100 g). Resin loading is accomplished by activation as the silyl triflate, which can accommodate even sterically encumbered secondary alcohols and phenols. Treatment with HF/pyridine for linker cleavage is mild, efficient, and amenable to an automated, large-scale distribution system. This platform delivers, minimally, 50 nmol of each small molecule derived from a diversity-oriented, split-pool synthesis on a per bead basis for use in both forward and reverse chemical genetic assays. This technology satisfies many requirements of a one bead-one stock solution approach to chemical genetics.

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalJournal of Combinatorial Chemistry
Volume3
DOIs
Publication statusPublished - May 2001

Keywords

  • PHASE ORGANIC-SYNTHESIS
  • SMALL MOLECULES
  • COUPLING REACTION
  • LINKERS
  • FUNCTIONALIZATION
  • MICROARRAYS
  • STRATEGIES
  • CHEMISTRY
  • RESINS

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