Generating Diverse Skeletons of Small Molecules Combinatorially

Martin D. Burke, Eric M. Berger, Stuart L. Schreiber

Research output: Contribution to journalArticlepeer-review


Lack of efficient access to collections of synthetic compounds that have skeletal diversity is a key bottleneck in the small-molecule discovery process. We report a synthesis strategy that involves transforming substrates with different appendages that pre-encode skeletal information, named σ elements, into products that have different skeletons with the use of common reaction conditions. With this approach, split-pool synthesis can be used to pre-encode skeletal diversity combinatorially and thereby generate such small molecules very efficiently. A split-pool synthesis of more than 1000 compounds produced overlapping, combinatorial matrices of molecular skeletons and appended building blocks in both enantiomeric and diastereomeric forms.

Original languageEnglish (US)
Pages (from-to)613-618
Number of pages6
Issue number5645
StatePublished - Oct 24 2003
Externally publishedYes

ASJC Scopus subject areas

  • General


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