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: 6385163
• 负责人: STEVEN D GOLDBERG
• 金额: $ 3.48万
• 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/6385163
• 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.

闭环复分解反应（RCM）作为一种由无环二烯前体形成环烯烃的强有力的合成方法而受到好评，这是由于在温和的反应条件下实现环化的官能团耐受的后过渡金属亚烷基催化剂的开发。 这种方法的扩展，包括合成环状乙烯基环氧乙烷，在有机合成中的通用中间体和许多大环化合物的天然产物的整体结构组成部分，已被提出。 终端乙烯基环氧乙烷作为基板的RCM的可行性将被确定的小型和中型碳环的合成，并通过直接观察推定的runtheium epoxyalkylidene中间体，通过1H NMR。 所提出的方法将允许通过传统的不对称环氧化方法不容易获得的环状1，3-二烯单环氧化物的容易的生产。 诱导肿瘤细胞分化为正常细胞的有效抗肿瘤抗生素根赤霉素的高度收敛的对映选择性合成将证明将乙烯基环氧乙烷部分并入复杂的医学上重要的大环结构中的能力。 所提出的路线可以很容易地修改为根赤霉素类似物的合成和QSAR研究，目前的信息很少。