This grant proposal """"""""Expanded Diversity Using Stereocontrolted Synthesis"""""""" describes a plan to establish a diversity-oriented synthesis core facility in the Chemistry Department at Boston University. Three major projects aimed at expanding chemical diversity are described. The projects constitute the blending of expertise of four investigators in key areas of asymmetric synthesis of complex molecules, heterocyclic chemistry, parallel synthesis and combinatorial chemistry, and bioorganic chemistry. The library synthesis core facility will develop new reaction methodologies for the stereocontrolled synthesis of complex molecule libraries. The first project described the stereoselective synthesis of libraries of both linear and macrocyclic polyketide and polypropionate-like molecules. New methodologies using both solid- and solution-phase chiral organosilane reagents will be developed in order to assemble these complex libraries. The second project focuses on the stereoselective synthesis and elaboration of novel scaffolds possessing positional and stereochemica] diversity in order to produce molecules with unusual shapes and stereocomplexity. This project includes the synthesis of functionalized spiroketals with positional and stereochemical diversification elements, the production of stereochemically diverse and highly-substituted pipecolic acid libraries, the synthesis of flavonoid-based libraries, and the synthesis of diverse heterocyclic molecules based on the tetrahydronapthyridine ring system. The third project emphasizes the assembly of unique libraries using convergent approaches. The focus of this study is the development of convergent diversity-oriented synthesis for the assembly of libraries of complex structures. The execution of these projects by the Library Synthesis Core will integrate the capabilities of cheminformatics, parallel chemical synthesis and purification, and analytical chemistry. These efforts will be supported by a separate Administrative/Compound Inventory core which will store the final libraries and provide them to members of the biology community through the Chemical Library Consortium for biological screening. The Boston University Center will develop fundamental, enabling methodologies for diversity-oriented synthesis which will greatly expand diversity of current compound libraries and thus produce lasting benefits for the biomedical sciences.
Showing the most recent 10 out of 100 publications
