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3,8-Diazabicyclo[3.2.1]octan-2-one Peptide Mimetics:  Synthesis of a Conformationally Restricted Inhibitor of Farnesyltransferase

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journal contribution
posted on 17.02.2001, 00:00 by Christopher J. Dinsmore, Jeffrey M. Bergman, Michael J. Bogusky, J. Christopher Culberson, Kelly A. Hamilton, Samuel L. Graham
A new synthesis of the 3,8-diazabicyclo[3.2.1]octan-2-one framework is described. Transannular enolate alkylation of piperazinone derivatives provides a flexible route to highly constrained bicyclic peptidomimetic synthons with substitution at the Cα position. The chemistry was used to produce a conformationally constrained farnesyltransferase inhibitor, which aided the elucidation of enzyme-bound conformation.