SYNTHESIS OF MEDICINALLY IMPORTANT NATURAL PRODUCTS

该提案描述了合成以下化合物的新方法： 几种含氢吡喃的天然产物， 治疗价值：二氢康巴汀（一种降胆固醇剂） 和米尔贝霉素/阿维菌素家族的螺缩酮单位， 抗生素（抗寄生虫药）。 制甲羟氨苄青霉素合成的特点是底物控制的反应， 用于建立所需构型的大环内酯 远程立体中心。 待制备的两种二羟基癸酸内酯 在本研究中可能是结构类型不 尚未报告。 目标分子的氢化萘部分 是通过一种新的串联迈克尔-羟醛的修改， 反应序列最近在这个实验室开发的。 提议研究的米尔贝霉素-阿维菌素部分使用 试剂控制反应（Sharpless环氧化和不对称 硼氢化）以建立远程立体中心， 芳环充当潜在的β-二羰基单元。 延伸 该策略用于合成四聚酮和更高级聚酮， 许多重要生物分子的结构亚基，将被 考察

This proposal describes novel methodology for the synthesis of several hydropyran-containing natural products of potential therapeutic value: dihydrocompactin (a hypocholesterolemic agent) and he spiroketal units of the milbemycin/avermectin family of antibiotics (antiparasitic agents). The compactin synthesis features substrate-controlled reactions on a macrocyclic lactone for establishing the desired configurations at remote stereocenters. Two dihydroxy decanolides to be prepared in this study are likely to be pro-drugs of a structural type not yet reported. The hydronapthalene portion of the target molecule is to be prepared via a modification of a new tandem Michael-aldol reaction sequence recently developed in this laboratory. The milbemycin-avermectin portion of the proposal study uses reagent-controlled reactions (Sharpless epoxidation and asymmetric hydroboration) to establish remote stereogenic centers while an aromatic ring serves as a latent beta-dicarbonyl unit. Extension of this strategy to the synthesis of tetra- and higher polyketides, structural subunits of many important biomolecules, will be examined.