Synthesis of Polyprionate Derived Natural Products

聚丙酸衍生天然产物的合成

• 批准号: 6922931
• 负责人: JAMES S. PANEK
• 金额: $ 29.72万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922931
• 关键词: Candida albicans; alkaloids; analog; antifungal agents; biological products; biotechnology; chemical reaction; chemical structure function; combinatorial chemistry; cytotoxicity; drug design /synthesis /production; drug screening /evaluation; low density lipoprotein receptor; method development; nitrogenous heterocyclic compound; organosilicon compound; propionates; pyridine; stereochemistry; transcription factor

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.

描述（由申请人提供）：本提案的基础是寻求在合成有机化学中开发新的反应方法，将其应用于具有生物活性的复杂天然产物，以及在合成和药物化学中具有根本重要性的研究。这包括努力开发用于对映体富集的有机硅烷的[4 + 2]-成环的新化学。一个广泛的调查，寻求评估功能化的有机硅烷试剂的立体选择性建设的二氢吡喃和四氢吡啶环系统，最终目标是在其应用中的合成。本论文将着重于二氢吡喃成环化学，对细胞毒性药物callipeltoside A和低密度脂蛋白受体转录激活剂的对映选择性合成进行研究。 本论文以生物碱205 B的合成为目标，研究了立体选择性合成含氮杂环化合物的新型成环方法。 一个收敛的，对映选择性的合成的有效的细胞毒性/抗真菌剂，leucascandrolide A将实现，并将适合于制备具有广泛多样的取代模式的侧链类似物。将组装杂环侧链类似物的小型集中文库，并评估其抑制白色念珠菌的有效性。