TOTAL SYNTHESIS OF AZADIRACHTIN

描述（由申请人提供）：这个项目是针对强效拒食剂印楝素(1)的全合成，从印楝树中分离出来，印楝树的提取物几个世纪以来一直被用作抗真菌、抗病毒和抗疟疾剂。这种具有挑战性的合成目标的令人生畏的性质为构建多环系统和拥挤的碳-碳键提供了新的策略，并有望发现、发明和发展新的合成技术。设计的针对印联素的趋同策略(1)是一个一般概念的变体，涉及构建代表分子十氢化萘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拴住和分子内拥挤的C8-C14碳-碳键的形成。预计拟议的工作将通过在合成有机化学和化学生物学方面的发现，影响制药和农业研究的一般领域，特别是传染病。

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.