Synthesis of Polyprionate Derived Natural Products

描述（由申请人提供）：本申请的基础是寻求在合成有机化学中发展新的反应方法，将其应用于生物活性复杂天然产物以及在合成化学和药物化学中具有基础重要性的研究。这包括为富对映体有机硅烷的[4 + 2]环化开发新的化学方法。一项广泛的研究，旨在评估功能化有机硅烷试剂的立体选择性构建二氢吡喃和四氢吡啶环体系，最终目标是在合成中的应用。对映体选择性合成细胞毒性药物callipeltoside A和低密度脂蛋白受体转录激活剂，重点是双氢吡喃环化化学。

DESCRIPTION (provided by applicant): The basis of this proposal seeks the to develop new reaction methods in synthetic organic chemistry, their application to biologically active complex natural products and investigations of fundamental importance in synthetic and medicinal chemistry. This includes efforts to develop new chemistry for the [4 + 2]-annulation of enantioenriched organosilanes. An extensive investigation seeking to evaluate functionalized organosilane reagents for the stereoselective construction of dihydropyrans and tetrahydropyridine ring systems with the eventual goal in their application in synthesis. The enantioselective synthesis of the cytotoxic agent callipeltoside A and the transcription activator of low density lipoprotein receptor will pursued with emphasis on the dihydropyran annulation chemistry. Novel annulation methodology for the stereoselective synthesis of nitrogen bearing heterocycles will be directed at the synthesis of alkaloid 205B. A convergent, enantioselective synthesis of the potent cytotoxic / antifungal agent, leucascandrolide A will be achieved and will suitable for the preparation of side chain analogs with widely diversified substitution patterns. A small focused library of heterocyclic sidechain analogs will be assembled and evaluated for their effectiveness in inhibiting Candida albicans.