Asymmetric Synthesis of Macrolide Antibiotics

描述(由申请人提供)：本提案详细介绍了高效不对称合成聚乙酸酯和聚丙酸酯衍生的大环内酯类抗生素的新的催化反应方法的开发，已有文件证明耐药细菌和真菌感染是一个迅速增长的重要问题。除了简单地实现此类化合物的合成，该提案的重点是提高这种合成努力的效率、最大限度地减少废物和经济可行性的前沿。因此，最终目标是实现实用和实用的化学，这将影响到新药物研究的发现和过程阶段。 这项提议既涉及前一个资助期最有希望的发现的延续和进一步发展，也涉及最近才开始的令人振奋的新方向。正在研究的反应有其统一的主题串联反应方法学。串联反应天生更有效，因为可以完成多个化学转化，并且可以在一次操作中建立多个立体中心。以这种方式，只使用现成的和环境友好的试剂，就可以以前所未有的效率合成目标天然产物的大片段。

DESCRIPTION (provided by applicant): This proposal details the development of new, catalytic reaction methodology for the efficient asymmetric synthesis of polyacetate- and polypropionate-derived macrolide antibiotics, It has been documented that drug-resistant bacterial and fungal infections represent a problem of rapidly growing importance. More than simply achieving syntheses of such compounds, the focus of the proposal is on advancing the frontiers of efficiency, waste-minimization 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. This proposal addresses both the continuation and further development of the most promising discoveries made in the previous funding period, as well as exciting new directions only recently initiated. The reactions under study have as their unifying theme tandem reaction methodology. Tandem reactions are inherently more efficient as multiple chemical transformations may be accomplished, and multiple stereogenic centers may be established in a single operation. In this fashion, large segments of the target natural products may be synthesized with unprecedented efficiency employing only readily available and environmentally benign reagents.