The Total Synthesis of Leucascandrolide A

说明(申请人提供)：银杏内酯A是一种新型的双重 从钙质海绵Leucascandra中分离的桥联18元大环内酯 珊瑚海新喀尔多尼亚海岸的洞穴。该化合物是一种高度 生物活性分子，对KB和P388细胞具有很强的细胞毒活性 以及对白色念珠菌的极佳抑制作用，白色念珠菌是一种致病酵母， 攻击艾滋病患者。这种方法非常灵活，并服从于 合成变种的构建。立体定义的糖基阴离子的使用 将提供大环内酯核的快速合成。它的中心部分是 亮氨酸内酯A侧链的合成将是一种 新型二卤代恶唑及其在两种高选择性钯催化体系中的应用 交叉偶联反应安装两个烷基侧链。最新进展 这种用于钯反应的新型前驱体不仅将促进 侧链的合成，但应开辟新的合成路线 在功能上更精细的恶唑系统，越来越 由于在各种天然产品中发现了它们，因此很重要。

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.