在傳統的藥物開發中，含硼分子顯少被列入考慮。但近來研究發現含硼藥物分子對其所作用之生化目標具有高度選擇性與高度活性等優點，使許多研究單位逐漸積極投入含硼藥物之開發，除了已經市售之硼酸抗癌藥物Bortezomib(VelcadeTM)外，目前也有愈來愈多的含硼化合物進入FDA之臨床測試階段，證明了含硼藥物的開發是一個非常值得注意的新領域。 本研究利用Ugi多組成反應(Ugi-4CR)於簡單的反應條件下合成硼酸與硼酯之Ugi化合物(Scheme 1)，其是以Methanol作為反應溶劑，並藉由微波方式加速其反應時間，此外，僅利用酸鹼萃取法及加熱抽高真空的方式，即可將粗產物純化，藉此可輕易地合成一系列之含硼Ugi化合物，並為含硼之衍生物提供了獨特的純化路徑。 此外，將合成出的兩系列化合物進行抗癌生物活性測試，發現有兩個化合物對於HepG2、MDA-MB231及A549之癌細胞皆具有抑制效果(Fig. 1)。 異腈化合物在材料、有機合成及藥物應用上十分具有利用價值，但目前所被合成之含硼異腈化合物僅有一個，且其合成步驟複雜、分子極不穩定，需保存在-30℃之油中，一旦取出，則會在六小時內快速分解。有鑑於此，將上述反應做調整，以TFE作為反應溶劑合成甲醯胺化合物，再將此官能基轉為異腈。即可以簡單步驟合成結構多元且具有對掌性中心之含硼異腈化合物(Scheme 2、Fig 2)，研究至今，僅需在冷藏環境下即可保存此化合物。 In this study, an Ugi four-component reaction (Ugi-4CR) utilizing formylphenylboronic acids or formylphenylboronate esters under mild condition is developed. The described reactions were performed in methanol and accelerated by employing microwave irradiation. In addition, the liquid-liquid acid/base extraction protocol for the purification and isolation of all reported final products were also included making this strategy suitable for the preparation of chemical libraries and provided a unique opportunity to access a broad range of boron-containing analogs. Two series of boron-containing products were synthesized and subsequently evaluated for their anti-cancer activity by the MTT assay. Two potential lead compounds were found to have potent activity against the HepG2, MDA-MB231, and A549 cancer cell lines, demonstrating the potential of this approach for use in the development of novel boron-containing pharmaceuticals.
