Development of Heterosubstituted Organotrifluoroborates

描述（申请人提供）：将研究烷氧基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。将探索这些反应的分子间和分子内版本。通过这些研究，我们将了解和欣赏这些不寻常的试剂，用于将烷氧基甲基亚基引入复杂的有机分子中，从而为将该功能单元安装到无环分子中提供新的范例。此外，适当功能化的底物提供了通过分子内反应形成氧杂环的独特途径的机会。以类似的方式，将制备氨甲基和氨乙基三氟硼酸盐，并将探索这些试剂在选择性有机合成中的范围和局限性。这一特定研究领域值得注意的是对映体纯的丙氨酸 b-阴离子等价物的开发。适当修饰的类似物的环化为氮杂环提供了前所未有的途径，适用于无数具有生物学意义的结构。同样，这些试剂的开发为构建不同类别的有机分子提供了一种独特的方法，因此将积极致力于这种化学的培养。为了证明所开发的试剂的价值及其在要求苛刻的系统中的可行性，几种天然产物已成为合成的目标。其中包括佐阿帕醇、生物碱 233F、nakadomarin A 和 halicyclamine 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。本文提出的研究解决了这一要求的一个方面。待探索的基础科学将提供多种可立即纳入药物发现过程以及工业规模合成的方案。此外，还提出了两种化合物（卤环胺 A 和 nakadomarin A）的合成，这两种化合物在初步测试中对几种不同的细胞系表现出选择性细胞毒性，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.