SYNTHESIS OF OPTICALLY PURE OXYGENATED CYCLOPENTANOIDS

拟议研究的具体目标是： (1)发展了一种有效的对映收敛方法 制备光学纯的中间体（保护的 4，5-二羟基-2-环戊烯-1-酮），其在合成 各种生物活性的含氧环戊烷酸。 (2)优化该中间体在开发中的利用 抗肿瘤碳环核苷，（-）-neplanocin A的合成， 通过探索一些合成途径。 (3)利用（1）中开发的中间体和化学 在（2）中探索了合成许多neplanocin A类似物（其中 基础成分已经改变）用于筛选抗肿瘤和/或 抗病毒剂。 (4)将（1）中所述的中间体转化为光学纯形式 “（-）-碳环核糖”的合成及其向抗生素的转化 （-）-红霉素。 (5)证明（1）中所述的中间体在本发明中的效用。 光学纯前列腺素和其他生物学物质的合成 有趣的天然产品。 (6)合成含有烯酮或 用于筛选潜在enont功能， 结构/活性关系，特别是作为DNA聚合酶 抑制剂，用于这类化合物作为抑制剂。

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.