TOTAL SYNTHESIS OF AZADIRACHTIN

印楝素的全合成

• 批准号: 6839439
• 负责人: K. C. NICOLAOU
• 金额: $ 46.93万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6839439
• 关键词: biotherapeutic agent; chemical structure function; chemical synthesis; intermolecular interaction; method development; plant extracts; stereochemistry; triterpenes

DESCRIPTION (provided by applicant): This program is directed toward the total synthesis of the powerful antifeedant agent azadirachtin (1) isolated from the neem tree whose extracts have been used for centuries as antifungal, antiviral, and antimalarial agents. The daunting nature of this challenging synthetic target invites new strategies for the construction of polycyclic systems and crowded carbon-carbon bonds and promises discovery, invention and development of new synthetic technologies. The designed convergent strategies toward azadirachtin (1) are variants of a general concept involving construction of advanced key building blocks representing the decalin and dihydrofuran domains of the molecule followed by tethering and intramolecular formation of the crowded C8-C14 carbon-carbon bond via radical or organometallic species. The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology.

描述(由申请人提供)：该计划旨在合成从印楝树中分离出来的有效拒食剂印木素(1)，其提取物几个世纪以来一直被用作抗真菌、抗病毒和抗疟疾药物。这一具有挑战性的合成目标的艰巨性质引发了构建多环系统和密集碳-碳键的新战略，并有望发现、发明和开发新的合成技术。针对印楝素(1)设计的收敛策略是一般概念的变体，涉及构建代表分子的十氢呋喃和二氢呋喃结构域的高级关键构建块，然后通过自由基或有机金属物种在分子内形成拥挤的C8-C14碳-碳键。拟议的工作预计将通过合成有机化学和化学生物学的发现，影响制药和农业研究的一般领域，特别是传染病。