Asymmetric Synthesis of Macrolide Antibiotics

描述（由申请人提供）：该提案详细描述了用于聚乙酸酯和聚丙酸酯衍生的大环内酯类抗生素的有效不对称合成的新催化反应方法的开发。据记载，耐药细菌和真菌感染代表了一个迅速增长的重要性问题。该提案的重点不仅仅是实现此类化合物的合成，而是推进此类合成工作的效率、废物最小化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。 该提案涉及上一个资助期内最有前途的发现的延续和进一步发展，以及最近才启动的令人兴奋的新方向。所研究的反应具有作为其统一主题的串联反应方法。串联反应本质上更有效，因为可以完成多个化学转化，并且可以在单个操作中建立多个立体中心。以这种方式，可以仅使用容易获得的和环境友好的试剂以前所未有的效率合成大片段的目标天然产物。

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.