SYNTHESIS OF HORMONAL, ANTIBIOTIC AND ANTIFUNGAL AGENTS

本文所述的程序针对以下的全合成： 一系列具有生物活性的天然产物 作为激素、抗生素和抗真菌剂。 还针对 天然离子载体和合成C2- 作为离子转运剂研究对称大二内酯， 手性催化剂所提出的合成方案旨在 为靶点提供便利的立体选择性途径 光学纯的分子。 这些路线应该是可行的 到克数量的目标和分子的生产， 其类似物用于生物筛选目的。 具体的合成目标包括红霉素 抗生素苷元、赤霉酸内酯B（1）和赤霉酸内酯A（2）; 离子载体抗生素茚达霉素（3）和灰螯铁蛋白（4）; 海洋软体动物代谢产物普洛乌普酮（5）是一种潜在的抑菌剂; 皮质类固醇肾上腺甾酮（6）和霉菌毒素展青霉素 （七）、 此外，一组"半天然"离子载体候选物 的非对映异构体类似物， 茚达霉素和灰螯铁蛋白。 C2-对称大二内酯 将从相应的氢吡喃制备10至13的引线 羟基酸单体通过二聚反应。 这些综合研究将强调特定的延伸， 应用的合成方法和战略， 上一个补助期。 分子内环加成和 环逆转过程，（3.3）-σ迁移重排， 杂环的合成，以及 富含立体化学的杂环模板是反复出现的主题。 经由烯烃硼氢化和锇化的无环立体控制将 被仔细审查，因为将螯合控制耦合的 亲核/亲电对。

The program described herein is directed at the total synthesis of a diverse set of natural products which show biological activity as hormonal, antibiotic, and antifungal agents. Also targeted are structural analogs of the natural ionophores and synthetic C2- symmetric macrodiolides for study as ion transport agents and chiral catalysts. The synthetic schemes presented are designed to provide expedient and stereoselective route, to the target molecules in optically pure form. The routes should be amenable to the production of gram quantities of the targets and molecular analogs thereof for biological screening purposes. Specific synthetic objectives included are the erythromycin antibiotic aglycones, erythronolide B (1) and erythronolide A (2); the ionophore antibiotics indanomycin (3) and griseochelin (4); the marine mollusk metabolite pulo'upone (5), a potential bacteriostat; the corticosteroid adrenosterone (6); and the mycotoxin patulin (7). In addition, a set of "semi-natural" ionophore candidates will be synthesized, including diastereomeric analogs of indanomycin and griseochelin. The C2-symmetric macrodiolides 10 leads to 13 will be prepared from the corresponding hydropyran hydroxy acid monomers by dimerization. These synthetic studies will stress the specific extension and application of the synthetic methods and strategies developed in the previous grant period. Intramolecular cycloaddition and cycloreversion processes, (3.3)-sigmatropic rearrangements for heterocycle synthesis, and the elaboration and fragmentation of heterocycle templates rich in stereochemistry are recurring themes. Acyclic stereocontrol via olefin hydroboration and osmylation will be scrutinized, as will chelation-controlled coupling of nucleophile/electrophile pairs.