This work was conducted under the aegis of the Harvard Center for Methodology and Library Development (NIGMS P50 GM069721). J.T.S. thanks Amgen Pharmaceuticals for a New Faculty Award. We thank Prof. Nabi Magomedov (Rochester University), Dr. Jacob Janey (Merck), Prof. Timothy J. Mitchison (Harvard Medical School), and Professor Stuart Schreiber (Broad Institute) for insightful discussions. The authors thank Max Narovlyansky for the preparation of the solid support, Dr. Nicola J. Tolliday (Broad Institute) for facilitation of screening, and Dr. Ralph Mazitschek (Broad Institute) for assistance with molecular modeling.
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Communication
A Structurally Diverse Library of Polycyclic Lactams Resulting from Systematic Placement of Proximal Functional Groups†
Article first published online: 15 FEB 2006
DOI: 10.1002/anie.200503341
Copyright © 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Mitchell, J. M. and Shaw, J. T. (2006), A Structurally Diverse Library of Polycyclic Lactams Resulting from Systematic Placement of Proximal Functional Groups. Angewandte Chemie International Edition, 45: 1722–1726. doi: 10.1002/anie.200503341
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Publication History
- Issue published online: 1 MAR 2006
- Article first published online: 15 FEB 2006
- Manuscript Received: 20 SEP 2005
Keywords:
- asymmetric synthesis;
- combinatorial chemistry;
- lactams;
- synthetic methods
Graphical Abstract
A short, linear sequence for the synthesis of complex small polycyclic lactams (see picture) is presented. The sequence, which is applied to the synthesis of a library of 529 compounds, is based on a catalytic, enantioselective cycloaddition between an oxazole and an aldehyde, so that the resultant compounds are enantiomerically pure and readily prepared in either stereochemical series.