ALLENES IN THE SYNTHESIS OF BIOACTIVE MOLECULES

这项提议的目标是发展环氧化化学。 改进的合成方法学，用于 高度功能化的生物分子的制备 利息。这是集中在生成相应的 烯二环氧化合物及其后续的亲核加成反应 这些活性中间体的反应。这件事的范围 化学，包括区域和立体化学特征以及 它在手性合成中的应用潜力将被定义为 分子间和分子内亲核试剂导致多官能团 分别为无环和杂环结构的产物。 在生物活性分子合成中的应用 包括皮质类固醇、吡咯烷和哌啶模型 生物碱、糖、亚烷基内酯和含氧复合体 四氢呋喃和-吡喃。海洋天然抗菌剂 产品比塞酮将成为一项综合研究的目标 说明了这种化学反应。将制定的方法学将 可用于合成所引用的各种类型的分子 和他们的类似物，特别是那些高度 功能化。其中许多化合物显示出重要的 包括抗生素在内的具有治疗价值的生物活性， 抗肿瘤、特定的酶抑制特性等 这项研究的结果应该有助于更好地理解 这些材料的性质和功能。

The goal of this proposal is to develop the epoxidation chemistry of allenes into improved synthetic methodology for the preparation of highly functionalized molecules of biological interest. This is focused on the generation of the corresponding allene diepoxides and the subsequent nucleophilic addition reactions of these reactive intermediates. The scope of this chemistry, including regio- and stereochemical features as well as its potential for use in chiral synthesis, will be defined for both inter- and intramolecular nucleophiles leading to polyfunctional products of acyclic and heterocyclic structure, respectively. Proposed applications to the synthesis of bioactive molecules include models for corticoid steroids, pyrrolidine and piperidine alkaloids, sugar, alkylidene lactones, and complex oxygenated tetrahydrofurans and -pyrans. The antimicrobial marine natural product Bissetone will be the target of a synthetic study illustrating this chemistry. The methodology to be developed will be of use in the synthesis of the various types of molecules cited and their analogs, especially those with a high degree of functionalization. Many of these compounds display important biological activity of therapeutic value including antibiotic, antineoplastic, specific enzyme inhibitory properties, etc. The results of this study should facilitate a better understanding of the nature and function of these materials.