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它们广泛的生物和药物活性以及它们复杂的结构和立体中心阵列有关。发展一种对映选择性的方法来合成安霉素类抗生素利福霉素S和链霉素D，氢化物类抗生素巴菲霉素A1和叶绿茶碱是本提案的主要目标。这些目标分子的选择是基于它们广泛的生物活性和挑战，代表了在它们的聚丙酸单位中发现的不同碳构型的阐述。近年来，人们对它们的研究和利用（以及一些半合成材料）产生了浓厚的兴趣

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.