ALLENES IN THE SYNTHESIS OF BIOACTIVE MOLECULES

该提案的目标是发展环氧化化学 的改进合成方法， 高度官能化的生物分子的制备 兴趣 这是集中在相应的一代 丙二烯二环氧化物和随后的亲核加成 这些反应中间体的反应。 这个范围 化学，包括区域和立体化学特征以及 它的潜力，用于手性合成，将被定义为两个 分子间和分子内亲核试剂， 无环和杂环结构的产物。 生物活性分子合成的建议应用 包括皮质类固醇、吡咯烷和哌啶模型 生物碱、糖、亚烷基内酯和复合氧化物 四氢呋喃和β-吡喃。 海洋天然抗菌剂 产品Bissetone将成为合成研究的目标 说明了这种化学反应。 拟制定的方法将 可用于合成所引用的各种类型的分子 及其类似物，特别是那些具有高度 功能化 这些化合物中的许多显示出重要的 具有治疗价值的生物活性，包括抗生素， 酶抑制特性、特异性酶抑制特性等。 这项研究的结果应有助于更好地了解 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.