Generating diverse skeletons of small molecules combinatorially.

Science
Authors
Keywords
Abstract

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 sigma 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.

Year of Publication
2003
Journal
Science
Volume
302
Issue
5645
Pages
613-8
Date Published
2003 Oct 24
ISSN
1095-9203
DOI
10.1126/science.1089946
PubMed ID
14576427
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