Nitropyrene Pollutants: Photochemical Transformations

大环内酯类和离子载体抗生素的合成一直被认为是合成有机研究中非常活跃的领域。这些靶分子的吸引力与它们广泛的生物学和药用活性以及它们的复杂结构和立体生成中心的排列有关。这项建议的主要目标是建立一种对映体选择性方法，用于合成阿霉素类抗生素利福霉素S和链霉素D，以及湿润类抗生素巴菲洛霉素A1和伊莱草素。这些目标分子的选择是基于它们广泛的生物活性和挑战，这代表了在它们的聚丙酸酯单元中发现的不同碳构型的阐述。近年来，人们对其研究和利用产生了极大的兴趣(以及一些半合成的 在这一领域产生的大量和不断增加的科学文献证明了作为治疗剂的药物)。已报道的这些目标的合成方法，就像许多其他聚丙酸酯体系一样，通常是基于羟醛和相关的化学。我们想要证明，环氧化物是一种可行的替代品，它们的使用可以纳入到这些非常重要的目标化合物的一般、灵活和立体选择性的路线中。我们的方法是一种简单和重复的方法，基于高烯丙醇的立体选择性环氧化，然后通过有机丙烷化学进行裂解。使用这种方法，我们可以控制甲基和羟基的构型，这是每个不同的聚丙酸酯单元的特征。 不仅可以实现本研究中提出的所需的化学转化。将审查关键反应的范围、局限性、立体选择性和机制含义。虽然我们的方法将应用于这些特定的目标，但原则上，它应该适用于许多其他聚丙酸酯体系，并将为合成类似物打开大门，这些类似物可以提供增加或修改生物活性和治疗潜力的机会。由于这是一种反复的方法，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.