ASYMMETRIC SYNTHESIS OF MACROLIDE ANTIBIOTICS

描述：(首席调查员)这份提案详细说明了 开发新的催化反应方法以获得高效的 聚醋酸酯大环内酯类抗生素的不对称合成 潜在的医药兴趣，如最近发现的强大 抗真菌海洋天然产物银杏内酯A已被 有记录表明，耐药细菌和真菌感染代表 一个日益重要的问题。不仅仅是实现 关于此类化合物的合成，该提案的重点是促进 效率、最大限度减少浪费和经济可行性的前沿 综合努力。因此，最终目标是实现 实用和实用的化学，这将影响到这一发现 以及研究新药剂的过程阶段。 正在考虑的这些反应有一个统一的主题 立体选择性和区域选择性过渡金属催化的羰化反应 直接合成适当保护/掩蔽的3，5-二甲基-3，5- 二羟基醛。这代表了(1，3，5…)多元醇 合成，将享受的好处，使羰基化 可行的工业规模工艺。

DESCRIPTION: (Principal Investigator's) This proposal details the development of new, catalytic reaction methodology for the efficient asymmetric synthesis of polyacetate-derived macrolide antibiotics of potential pharmaceutical interest such as recently discovered powerfully anti-fungal marine natural product leucascandrolide A. It has been documented that drug-resistant bacterial and fungal infections represent a problem of rapidly growing importance. More than simply achieving synthesis of such compounds, the focus of the proposal is on advancing the frontiers of efficiency, waste-minimizing and economic viability of such synthetic efforts. The ultimate goal is thus the realization of practicable and practical chemistry that will affect both the discovery and process phases of research into new medicinal agents. These reactions under consideration have as their unifying theme the stereo-and regioselective transition metal-catalyzed carbonylation of alkenes leading to the direct synthesis of suitably protected/masked 3,5- dihydroxyaldehydes. This represents a novel approach to (1,3,5...) polyol synthesis that will enjoy the benefits that render carbonylation a feasible industrial-scale process.