NSF Award
0455072
The overall objectives of this proposal are to develop solid and liquid phase silica based synthesis supports, as well as a range of linkers, that can be completely and cleanly removed by "volatilization," leaving only the desired synthetic product(s) in the reaction vessel following the complete decomposition of the support to volatile materials. Elimination of the final separation step required following cleavage of the desired product from traditional solid supports during the combinatorial synthesis of hundreds to thousands of individual compounds will greatly decrease the time required for the extraction of such samples following their cleavage and will increase the yield and purity of the desired products (especially when preparing small amounts of very large numbers of individual compounds). Furthermore, this approach will enable 96 or 384 well plates utilized in automated combinatorial array synthesizers to be used for both synthesis and "mother" plate storage. The initial materials to be studied as potential volatilizable supports will be functionalized silica gels and polysiloxane oils, removable through complete decomposition to volatile materials through the action of aqueous and/or anhydrous hydrogen fluoride during the final cleavage step. Silica gel is completely and cleanly transformed into tetrafluorosilane (SiF4, boiling point = -86 C), while polysiloxane oils are decomposed into difluorodimethyl- and fluorotrimethylsilane. Such volatile decomposition products can be readily removed through their decomposition and/or neutralization to harmless materials by in-line CaO/Ca(OH)2 traps.<br/><br/> With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Richard A. Houghten, of the Department of Chemistry at the Torrey Pines Institute for Molecular Studies. Professor Houghten is developing novel methods for the synthesis of organic compounds, wherein chemical reactions of molecules attached to solid or liquid "supports" are followed by complete removal of the support through its chemical conversion to volatile products. These methods allow one to exploit the versatility of "solid-phase" syntheses while eliminating many of the undesirable processing features of such reactions, potentially greatly decreasing the time required and increasing the yield and purity of the desired products, especially when preparing small amounts of very large numbers of individual compounds. Additionally, this approach will enable the ready and cost effective solid phase synthesis of semi-preparative and preparative scale quantities of compounds (grams to potentially multiple kilograms) in academic and industrial laboratories, addressing a long standing limitation of existing solid phase synthesis supports.
