EXPLORATION OF VINYLOXIRANES IN RING-CLOSING METATHESIS

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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.