Development of Heterosubstituted Organotrifluoroborates

杂取代有机三氟硼酸盐的开发

• 批准号: 7287941
• 负责人: GARY A MOLANDER
• 金额: $ 29.59万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-07 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287941
• 关键词: Address; Alanine; Alkaloids; Anions; Area; Basic Science; Biological; Biological Factors; Cell Line; Chemistry; Class; Complex; Coupling; Cyclization; Development; Exhibits; Facility Construction Funding Category; Family; Funding; Goals; Investigation; Lead; Methods; Nitrogen; Object Attachment; Organic Synthesis; Oxygen; Pathway interactions; Pharmacologic Substance; Procedures; Process; Range; Reaction; Reagent; Research; Route; Site; Structure; System; Testing; Time; Transition Elements; analog; caN protocol; cancer therapy; chemical synthesis; cost; halicyclamine A; improved; interest; nakadomarin A; novel; programs; zoapatanol

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.

描述（由申请人提供）：将对烷氧基甲基三氟硼酸盐的合成及其在过渡金属催化的偶联反应中的应用进行研究。将探讨这些反应的分子间和分子内版本。通过这些研究，我们将获得对这些不寻常的试剂的理解和欣赏，用于将烷氧基甲基亚基引入到复杂的有机分子中，从而为将这种功能单元安装到无环分子中提供新的范例。此外，适当官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，氨甲基和氨乙基三氟硼酸盐将被制备，这些试剂在选择性有机合成的范围和限制将被探索。在这一特定的研究领域中，值得注意的是开发对映体纯的丙氨酸b-阴离子等价物。适当取代的类似物的环化提供了一个前所未有的进入氮杂环，适用于无数的生物学意义的结构。同样，这些试剂的发展提供了一种独特的方法来构建不同类别的有机分子，因此，这种化学的培养将被积极追求。作为一种手段，以证明开发的试剂的价值和他们在苛刻的系统中的生存能力，几个天然产物已被定向合成。这些包括zoapatanol，生物碱233 F，nakadomarin A和halicyclamine A。以成本和时间有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几种可以立即纳入药物发现过程以及工业规模合成的方案。此外，提出了两种化合物（halicyclamine A和nakadomarin A）的合成方法，这两种化合物在初步试验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。