Stereochemical Studies of Nucleosides and Nucleotides

人们普遍认为，核苷糖基键周围的反式构象是核苷和核苷酸与利用它们的各种酶相互作用的重要决定因素之一。为了阐明这种相互作用的立体化学性质，环状核苷将是有用的。在这方面，糖基扭角被碳桥固定在适当程度的环核苷被认为是有用的模型。本文综述了嘧啶类和嘌呤类c -环核苷的合成结果。介绍了它们的一些磷酸盐的合成及其某些生物学特性。碳桥嘧啶环核苷的合成。制备了以下新化合物：5′-脱氧-6,5′-甲尿嘧啶；2“-deoxy-6 2”-ethanouridine;2“-deoxy-6 2”-methanouridine;6、2 ' -methanouridine;6、3 ' -methanouridine;6、3 ' -methanocytidine;6、3 ' -methanothymidine;6、5 ' -cyclo-2 ', 5 ' 5 ' -di-deoxyuridine 6日-cyclo5的脱氧胸苷;6,5'-环-5'-脱氧-5'-羟乙基尿嘧啶及其相关中间体。5'-脱氧-6,5'-环嘧啶的2',3'-环磷酸是胰腺核糖核酸酶（RNase）的底物。3'-磷酸是强抑制剂。这意味着核糖核酸酶识别反形式的嘧啶核苷。碳桥嘌呤环核苷的合成。新合成的化合物有：2′-脱氧-8,2′-乙醇腺苷；3“-deoxy-8 3”-ethanoadenosine;8、2 ' -ethanoadenosine;2“-deoxy-8 2”-methanoadenosine;8、2 ' -methanoadenosine;8,2'-甲烷鸟苷及其α异头物。8,2'-环腺苷是腺苷脱氨酶的底物，而8,3'-环腺苷则不是。5'-羟基的构象对底物与酶的结合也可能是重要的。对部分环核苷进行了抗肿瘤（L1210）和抗病毒（hsv - 1）性能测试。在100 <微> g/ml水平下，均无明显活性。

It has been generally recognized that the syn-anti conformation around the glycosylic linkages of nucleosides is one of the important determinants in the interaction of nucleosides and nucleotides with various enzymes utilizing them. To elucidate the stereochemistry of such interactions, the cyclonucleosides would be useful. In this respect, cyclonucleosides where the glycosyl torsion angle is fixed in an appropriate degree by the carbon bridge is regarded as useful model. This report summarized the result of synthesis of C-cyclonucleosides of pyrimidines and purines. Synthesis of some their phosphates and certain biological properties are also described.1. Synthesis of carbon-bridged pyrimidine cyclonucleosides.The following new compounds have been prepared: 5'-deoxy-6,5'-methanouridine; 2'-deoxy-6,2'-ethanouridine; 2'-deoxy-6,2'-methanouridine; 6,2'-methanouridine; 6,3'-methanouridine; 6,3'-methanocytidine; 6,3'-methanothymidine; 6,5'-cyclo-2',5'-di-deoxyuridine 6,5'-cyclo5'-deoxythymidine; 6,5'-cyclo-5'-deoxy-5'-hydroxyethyluridine, and related intermediates.2. The 2',3'-cyclic phosphates of 5'-deoxy-6,5'-cyclouridines were the substrates of pancreatic ribonuclease (RNase). The 3'-phosphates were strong inhibitors. This means that the RNase recognizes the anti form of the pyrimidine nucleosides.3. Synthesis of carbon-bridged purine cyclonucleosides.The following compounds were newly synthesized: 2'-deoxy-8,2'-ethanoadenosine; 3'-deoxy-8,3'-ethanoadenosine; 8,2'-ethanoadenosine; 2'-deoxy-8,2'-methanoadenosine; 8,2'-methanoadenosine; 8,2'-methanoguanosine and its alpha anomer. The 8,2'-cyclo-adenosines were the substrates of adenosine deaminase whereas the 8,3'-compound was not. The conformation of the 5'-hydroxyl group may also be important for the binding of the substrate to the enzyme.4. Some of the cyclonucleosides were tested for the antitumor (L1210) and antiviral (HSV-I) properties. None of them showed distinct activities to a level of 100 <micro> g/ml.