Generating diverse skeletons of small molecules combinatorially |
| |
Authors: | Burke Martin D Berger Eric M Schreiber Stuart L |
| |
Affiliation: | Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Institute of Chemistry and Cell Biology, Harvard University, Cambridge, MA 02138, USA. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|