The Total Synthesis of Leucascandrolide A

性状（由申请人提供）：亮白Candrolide A是一种新的双 从钙质海绵Leucascandra中分离的桥连18元大环内酯 沿着珊瑚海的新卡尔多尼亚海岸。该化合物是一种高度 生物活性分子，对KB和P388细胞显示出强的细胞毒活性 以及对白色念珠菌的优异抑制，白色念珠菌是一种致病酵母， 袭击艾滋病患者。该方法具有高度灵活性， 合成变体的构建。立体限定的糖基阴离子的使用 将提供大环内酯核心的快速合成。的中心部分， 合成的无色Candrolide A侧链将是一个发展 新的二卤代恶唑及其在两种高选择性钯催化的 交叉偶联反应以安装两个烷基侧链。发展 这种新型的钯反应前体不仅有助于 侧链的合成，但应开辟新的合成路线， 功能上更精细的恶唑体系， 重要的是由于它们在各种天然产物中的发现。

DESCRIPTION (provided by applicant): Leucascandrolide A is a novel doubly bridged 18-membered macrolide isolated from the calcareous sponge Leucascandra caveolata along the coast of New Caldonia, Coral Sea. The compound is a highly bioactive molecule, showing strong cytotoxic activity towards KB and P388 cells as well as excellent inhibition of Candida albicans, a pathogenic yeast that attacks AIDS patients. The approach is highly flexible and amenable to the construction of synthetic variants. The use of stereodefined glycosyl anions will provide a rapid synthesis of the macrolide core. The center piece of the synthesis of the leucascandrolide A side chain will be the development of a novel dihalooxazole and its use in two highly selective palladium-catalyzed cross coupling reactions to install the two alkyl side chains. The development of this novel precursor for palladium reactions will not only facilitate the synthesis of the side chain, but should open new routes for the synthesis of functionally more elaborate oxazole systems which are becoming increasingly important due to their discovery in a variety of natural products.