Development of Heterosubstituted Organotrifluoroborates

杂取代有机三氟硼酸盐的开发

• 批准号: 7494153
• 负责人: GARY A MOLANDER
• 金额: $ 29.16万
• 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/7494153
• 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甲酸酯的合成及其在过渡金属催化的偶联反应中的效用进行研究。将探索这些反应的分子间和分子内版本。通过此类研究，我们将了解和欣赏这些不寻常的试剂，以将烷氧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了新的范式。此外，适当功能化的底物为通过分子内反应提供独特的氧杂环途径提供了机会。以类似的方式，将制备氨基甲基甲基和氨基甲基三氟甲酸酯，并将探索这些试剂在选择性有机合成中的范围和局限性。在这一特定研究方面引人注目的将是对映体纯Alanine B-Anion等效物的发展。适当装饰的类似物的环化为氮杂环提供了前所未有的进入，该进入适用于无数生物学意义的结构。同样，这些试剂的开发为建造各种有机分子的构建提供了一种独特的方法，因此将积极追求这种化学的培养。作为证明开发试剂的价值及其在苛刻系统中的生存能力的一种手段，已经将几种天然产品用于合成。其中包括Zoapatanol，生物碱233F，Nakadomarin A和HalyclclamineA。以成本和时间效率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协议，这些方案可以立即纳入药品发现过程以及工业规模的综合。此外，提出了两种化合物（Halicyclamine A和Nakadomarin A）在初步测试中针对几种不同细胞系具有选择性细胞毒性的合成，并且这些分子可以用作治疗癌症和其他伴侣的铅化合物。