Scientific Publications

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

Publication TypeJournal Article
AuthorsWong, JC, Sternson SM, Louca JB, Hong R., and Schreiber SL
AbstractModular 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.
Year of Publication2004
JournalChemistry & biology
Volume11
Issue9
Pages1279-91
Date Published (YYYY/MM/DD)2004/09/01
ISSN Number1074-5521
DOI10.1016/j.chembiol.2004.07.012
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/15380188?dopt=Abstract