EXPLORATION OF VINYLOXIRANES IN RING-CLOSING METATHESIS

闭环歧化反应(RCM)是一种以无环二烯为原料合成环状烯烃的有效合成方法，这是由于发展了具有官能团耐受性的后过渡金属亚烷基催化剂，可以在温和的反应条件下进行环化反应。已提议将这一方法扩展到包括环氧乙烷的合成、有机合成中的多种中间体和许多具有药理活性的大环天然产物的整体结构成分。作为RCM底物的末端聚氧环氧烷的活性将取决于中小尺寸碳环的合成，以及通过~1H核磁共振直接观察假定的Runtheium环氧亚烷基中间体。建议的方法将允许容易地生产环状1，3-二烯单环氧化物，这是传统的不对称环氧化方法不容易获得的。高效的抗肿瘤抗生素自由基的高度收敛的对映选择性合成，可以诱导肿瘤细胞向正常细胞分化，将展示将聚氧乙烯氧烷部分结合到复杂的医学上重要的大环结构中的能力。建议的路线可以很容易地修改，用于合成自由基类似物和目前几乎没有相关信息的QSAR研究。

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.