SYNTHESIS OF OPTICALLY PURE OXYGENATED CYCLOPENTANOIDS

建议进行的研究的具体目的如下： (1)发展了一种高效的对映体收敛方法 生产光学纯中间体(受保护的中间体 4，5-二羟基-2-环戊烯-1-酮)在合成环戊烯-1-酮中具有广泛的用途 具有生物活性的含氧环烯类化合物的种类。 (2)该中间体在开发中的优化利用 抗肿瘤碳环核苷(-)-奈普兰星A的合成， 通过探索一些合成途径。 (3)在(1)中开发的中间体的利用及其化学 在(2)中探索以合成许多奈普兰菌素A类似物(其中 碱基成分已改变)用于筛选为抗肿瘤和/或 抗病毒药物。 (4)将(1)中提到的中间体转化为光学纯形式 “(-)-碳环核糖”及其向抗生素的转化 (-)-阿司匹林。 (5)第(1)款所述中间体的效用演示 光学纯前列腺素及其他生物制剂的合成 有趣的天然产品。 (6)含有烯酮或 用于筛查的潜在Enont功能，以努力确定 结构/活性关系，特别是作为DNA聚合酶 作为抗肿瘤药物的这类化合物的抑制剂。

The specific aims of the research proposed are: (1) The development of an efficient method for the enantioconvergent production of an optically pure intermediate (a protected 4,5-dihydroxy-2-cyclopenten-1-one) of broad utility in the synthesis of a variety of biologically active oxygenated cyclopenanoids. (2) Optimization of the utilizaton of this intermediate in the development of a synthesis of the antitumor carbocyclic nucleoside, (-)-neplanocin A, by exploration of a number of synthetic pathways. (3) Utilization of the intermediate developed in (1) and the chemistry explored in (2) to synthesize a number of neplanocin A analogues (in which the base component has been altered) for screening as antitumor and/or antiviral agents. (4) Conversion of the intermediate noted in (1) into an optically pure form of "(-)-carbocyclic ribose" and conversion of this to the antibiotic (-)-aristeromycin. (5) Demonstration of the utility of the intermediate noted in (1) in the synthesis of an optically pure prostaglandin and other biologically interesting natural products. (6) Synthesis of simplified prostanoid targets which contain enone or latent enont functionality for screening in an effort to establish structure/activity relationships, particularly as DNA polymerase inhibitors, for compounds of this class as antineoplastic agents.