Development of Heterosubstituted Organotrifluoroborates

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DESCRIPTION (provided by applicant): Studies will be carried out on the synthesis of alkoxymethyltrifluoroborates and their utility in transition metal catalyzed coupling reactions. Both intermolecular and intramolecular versions of these reactions will be explored. Through such studies, we will gain an understanding and appreciation of these unusual reagents for the introduction of alkoxymethyl subunits into complex organic molecules, thus providing a new paradigm for the installation of this functional unit into acyclic molecules. Additionally, suitably functionalized substrates provide the opportunity for a distinctive route to oxygen heterocycles via intramolecular reactions. In a similar manner, aminomethyl- and aminoethyltrifluoroborates will be prepared, and the scope and limitations of these reagents in selective organic synthesis will be explored. Of notable interest in this particular line of research will be the development of enantiomerically pure alanine b-anion equivalents. Cyclization of appropriately ornamented analogues provides an unprecedented entry to nitrogen heterocycles that is applicable to myriad structures of biological significance. Again, the development of these reagents affords a unique approach to the construction of diverse classes of organic molecules, and the cultivation of this chemistry will thus be aggressively pursued. As a means to demonstrate the value of the developed reagents and their viability in demanding systems, several natural products have been targeted for synthesis. These include zoapatanol, alkaloid 233F, nakadomarin A, and halicyclamine A. The discovery of new Pharmaceuticals in a cost and time efficient manner requires the development of new and improved methods for their chemical synthesis. The research proposed herein addresses one aspect of this requirement. The basic science to be explored would make available several protocols that could be immediately incorporated into the pharmaceutical discovery process as well as industrial scale synthesis . Additionally, syntheses of two compounds (halicyclamine A and nakadomarin A) that exhibit selective cytoxicity against several different cell lines in preliminary tests are proposed, and these molecules could serve as lead compounds for the treatment of cancer and perhaps other afflictions.