Development of Heterosubstituted Organotrifluoroborates

描述(申请人提供)：将研究烷氧甲基三氟硼酸盐的合成及其在过渡金属催化偶联反应中的应用。这些反应的分子间和分子内版本都将被探索。通过这些研究，我们将了解和评价这些将烷氧甲基亚基引入到复杂有机分子中的特殊试剂，从而为将这种功能单元安装到无环分子中提供一个新的范式。此外，合适的官能化底物提供了通过分子内反应生成氧杂环的独特途径。以类似的方式，将制备氨甲基和氨基乙基三氟硼酸盐，并将探索这些试剂在选择性有机合成中的范围和局限性。在这一特定研究领域中值得注意的是开发对映体纯的丙氨酸b-阴离子等效物。适当修饰的类似物的环化反应提供了一个前所未有的进入氮杂环的途径，适用于无数具有生物意义的结构。同样，这些试剂的发展为构建不同类别的有机分子提供了一种独特的方法，因此这种化学的培养将被积极地追求。作为一种证明所开发试剂的价值及其在要求苛刻的系统中的生存能力的手段，几种天然产物已成为合成的目标。这些药物包括Zoapatol、生物碱233F、Nakadomarin A和卤代环胺A。以成本和时间高效的方式发现新药物需要开发新的和改进的化学合成方法。这里提出的研究解决了这一要求的一个方面。将要探索的基础科学将提供几项协议，这些协议可以立即纳入药物发现过程以及工业规模的合成。此外，还建议合成两种在初步试验中对几种不同细胞株具有选择性细胞毒性的化合物(双环胺A和中草药甲素)，这些分子可以作为治疗癌症和其他疾病的先导化合物。

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.