Synthetic Studies on Hennoxazole A with Antivirus Activity

Hennoxazole（A-D）是由Higa等从冲绳海绵Polyfibrosongia sp.中分离得到的一个新化合物。该化合物具有结构上独特的双恶唑，与四氢吡喃/半缩酮和三烯相邻。我们希望通过三个关键中间体，四氢吡喃，双恶唑和三烯部分合成亨立唑A。以（R）-3-羟基-2-甲基丙酸甲酯为原料，通过烯丙基溴和乙烯基锡的钯偶联反应合成了三烯，以（S）-1，2-二氢吡喃为原料，通过（S）-1，2-二氢吡喃为原料，合成了四氢吡喃/半缩酮开环的甲基酮，并对甲基酮的结构进行了研究。上述甲基酮向四氢吡喃/半缩酮的转化正在积极进行中。

Hennoxazoles (A-D) were isolated by Higa and coworkers from the okinawan sponge, Polyfibrospongia sp. Hennoxazole A has been shown to have interesting antivirus and antiinflammatory activities. The compound possesses a stucturally unique bisoxazole adjacent to a tetrahydropyran/hemiketal and a triene. We hoped to synthesis Hennexazole A via three key intermediates, tetrohydropyran, bisoxazole, and triene moieties. Our work concerned with the attempted synthesis of suitably protected forms of tetrohydropyran and triene moieties.The synthesis of the triene starting from methyl (R)-3-hydroxy-2-methylpropionate was accomplished by cross-coupling of the allyl bromide and the vinyltin using palladium.The methyl ketone, the ring opened form of the tetrahydropyran/hemiketal moiety was synthesized from (S)-1,2,4-butanetriol in several steps.Conversion of the above methyl ketone to the tetrahydropyran/hemiketal is actively underway.