Modular synthesis and preliminary biological evaluation of stereochemically diverse 1,3-dioxanes

Chemistry & Biology
Jason C WongStuart L Schreiber

Abstract

Modular synthesis and substrate stereocontrol were combined to furnish 18,000 diverse 1,3-dioxanes whose distribution in chemical space rivals that of a reference set of over 2,000 bioactive small molecules. Library quality was assessed at key synthetic stages, culminating in a detailed postsynthesis analysis of purity, yield, and structural characterizability, and the resynthesis of library subsets that did not meet quality standards. The importance of this analysis-resynthesis process is highlighted by the discovery of new biological probes through organismal and protein binding assays, and by determination of the building block and stereochemical basis for their bioactivity. This evaluation of a portion of the 1,3-dioxane library suggests that many additional probes for chemical genetics will be identified as the entire library becomes biologically annotated.

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Citations

Jan 20, 2009·Nature Chemical Biology·Benjamin Z StantonStuart L Schreiber
Aug 16, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·H Charles ManningNathan J Mutic
May 15, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Grant N Wheeler, André W Brändli
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Dec 3, 2014·Current Opinion in Chemical Biology·Andrew J Rennekamp, Randall T Peterson
May 25, 2006·Chemistry & Biology·James E BradnerAngela N Koehler
May 28, 2013·Chemistry & Biology·Hongyan SunShao Q Yao
Dec 22, 2009·Molecular BioSystems·Benjamin Z Stanton, Lee F Peng
Feb 9, 2010·Nature Chemical Biology·James E BradnerRalph Mazitschek
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Aug 2, 2006·Molecular BioSystems·Mahesh UttamchandaniShao Q Yao
Apr 15, 2008·Organic Letters·O DemmerH Kessler
Jun 15, 2006·Chemical Reviews·Daniel P Walsh, Young-Tae Chang

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