EXPLORATION OF VINYLOXIRANES IN RING-CLOSING METATHESIS

乙烯基环氧乙烷在闭环复分解中的探索

• 批准号: 6647364
• 负责人: STEVEN D GOLDBERG
• 金额: $ 4.42万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6647364
• 关键词: alkenes; antineoplastic antibiotics; chemical synthesis; cyclization; drug design /synthesis /production; enzyme inhibitors; ethylene oxide; lactones; nuclear magnetic resonance spectroscopy; stereochemistry

Ring-closing metathesis (RCM) has received acclaim as a powerful synthetic method for the formation of cyclic olefins from acyclic diene precursors, due to the development of functional group tolerant late transition metal alkylidene catalysts that effect cyclization under mild reaction conditions. Expansion of this methodology to include the synthesis of cyclic vinyloxiranes, versatile intermediates in organic synthesis and integral structural components of numerous macrocyclic pharmacologically potent natural products, has been proposed. The viability of terminal vinyloxiranes as substrates for RCM will be determined by the synthesis of small and medium sized carbocycles, and by direct observation of the putative runtheium epoxyalkylidene intermediate by 1H NMR. The proposed method will allow for the facile production of cyclic 1,3-diene monoepoxides not readily accessible by traditional asymmetric epoxidation methods. The highly convergent enantioselective synthesis of potent antitumor antibiotic radicicol, which induces the differentiation of tumor cells into normal cells, will demonstrate the ability to incorporate the vinyloxirane moiety into complex medicinally important macrocyclic structures. The proposed route may be readily modified for the synthesis of analogs of radicicol and QSAR studies for which there is little current information.

闭合环复合反应（RCM）作为一种由无环二烯前体生成环烯烃的有效合成方法而受到好评，这是由于在温和的反应条件下开发了具有官能团耐受性的晚期过渡金属烷基烯催化剂。已经提出了该方法的扩展，以包括环乙烯基氧烷的合成，有机合成中的多功能中间体和许多大环有效的天然产物的整体结构成分。末端乙烯基氧烷作为RCM底物的可行性将通过中小碳环的合成，以及通过1H NMR直接观察推测的环氧烷基烯钌中间体来确定。所提出的方法将允许容易地生产环1,3-二烯单环氧化物不容易通过传统的不对称环氧化方法。强效抗肿瘤抗生素radicicol的高度收敛的对端选择性合成，诱导肿瘤细胞向正常细胞分化，将证明将乙烯基氧烷部分纳入复杂的药用重要的大环结构的能力。所提出的路线可以很容易地用于合成自由基类似物和QSAR研究，目前的信息很少。