ASYMMETRIC SYNTHESIS OF MACROLIDE ANTIBIOTICS

描述：（主要研究者）本提案详细说明了 开发新的催化反应方法， 聚乙酸酯衍生的大环内酯类抗生素的不对称合成 潜在的药物利益，如最近发现的有力 抗真菌海洋天然产物白藜芦醇内酯A。已经 证明耐药细菌和真菌感染代表了 一个重要性迅速增长的问题。不仅仅是实现 合成此类化合物，建议的重点是推进 这些技术的效率、最大限度减少浪费和经济可行性的前沿 合成的努力。最终目标是实现 实用和实用的化学，这将影响发现， 以及研究新药物的各个阶段。 考虑中的这些反应的统一主题是： 立体和区域选择性过渡金属催化羰基化 导致直接合成适当保护/掩蔽的3，5-二烯的烯烃 二羟醛。这代表了（1，3，5.）多元醇 合成，将享有的好处，使羰基化， 可行的工业规模的过程。

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.