Generating diverse skeletons of small molecules combinatorially.
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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
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Journal | Science
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Volume | 302
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Issue | 5645
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Pages | 613-8
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Date Published | 2003 Oct 24
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ISSN | 1095-9203
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DOI | 10.1126/science.1089946
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PubMed ID | 14576427
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