Nitropyrene Pollutants: Photochemical Transformations

大环内酯和离子载体抗生素的合成仍然被认为是有机合成研究的一个非常活跃的领域。这些靶分子的吸引力与其广泛的生物学和医学活性以及其复杂的结构和立体中心阵列有关。本提案的主要目标是开发用于合成安莎霉素抗生素利福霉素S和静脉曲张链球菌素D以及乙内酰抗生素巴弗洛霉素A1和elaiophylin的对映选择性方法。这些靶分子的选择是基于其广泛的生物活性和代表在其聚丙酸酯单元中发现的不同碳构型的阐述的挑战。近年来，对它们的研究和利用（以及一些半合成的 衍生物）作为治疗剂的应用已经通过在该领域产生的广泛和不断增加的科学文献得到证实。与许多其他聚丙酸酯系统一样，这些目标的报道合成方法通常基于羟醛和相关化学。我们希望证明环氧化物是一种可行的替代品，它们的使用可以纳入这些非常重要的目标化合物的通用，灵活和立体选择性路线。我们的方法是一个简单和重复的，是基于高烯丙醇的立体选择性环氧化，然后通过有机铝烷化学裂解。通过这种方法，我们可以控制表征每个不同聚丙酸酯单元的甲基和羟基的构型。 不仅在这项研究中提出的所需的化学转化将被完成。的范围，限制，立体选择性和关键反应的机械影响将被检查。虽然我们的方法将应用于这些特定的目标，原则上，它应该适用于许多其他聚丙酸酯系统，并将打开大门的合成类似物，可以提供机会，增加或修改的生物活性和治疗潜力。由于这是一种迭代方法，从长远来看，它可能适合于自动化和组合应用。

The synthesis of macrolide and ionophore antibiotics continues to be regarded as a very active area of synthetic organic research. The attractiveness of these target molecules is related to their broad range of biological and medicinal activity together with their complex structure and array of stereogenic centers. The development of an enantioselective methodology for the synthesis of the ansamycin antibiotics rifamycin S and streptovaricin D, and the hygrolide antibiotics bafilomycin A1 and elaiophylin is the main goal of this proposal. The selection of these target molecules is based on their extensive biological activity and the challenge that represents the elaboration of the different carbon configurations found in their polypropionate units. In recent years a great interest in their study and utilization (and that of some semisynthetic derivatives) as therapeutic agents has been evidenced by the extensive and increasing scientific literature being generated in this area. The reported synthetic approaches to these targets, as for many other polypropionate systems, have been usually based on aldol and related chemistry. We would like to demonstrate that epoxides are a viable alternative and that their use can be incorporated into a general, flexible and stereoselective route to these very important target compounds. Our approach is a simple and reiterative one, and is based on the stereoselective epoxidation of homoallylic alcohols followed by their cleavage via organoalane chemistry. With this methodology we can control the configuration of the methyl and hydroxyl groups which characterize each distinct polypropionate unit. Not only the desired chemical transformations proposed in this study will be accomplished. The scope, limitations, stereoselectivity and mechanistic implications of the key reactions will be examined. Although our methodology will be applied to these specific targets, in principle, its should be applicable to many other polypropionate systems and will open the door for the synthesis of analogues which can presents opportunities for increased or modified biological activity and therapeutic potential. Since this is a reiterative approach, in the long term, it may be suitable for automation and combinatorial application.