Stereochemical Studies of Nucleosides and Nucleotides

人们普遍认为，核苷糖基键周围的顺反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，环己糖苷将是有用的。在这方面，其中糖基扭转角通过碳桥以适当程度固定的环己基糖苷被认为是有用的模型。本文综述了嘧啶和嘌呤的C-环己基糖苷的合成结果。本文还介绍了它们的一些磷酸酯的合成及某些生物学性质.碳桥嘧啶环核苷的合成：5 ′-脱氧-6，5 ′-甲尿苷; 2 ′-脱氧-6，2 ′-乙尿苷; 2 ′-脱氧-6，2 ′-甲尿苷; 6，2 ′-甲尿苷; 6，3 ′-甲尿苷; 6，3 ′-甲胸苷; 6，5 ′-环-2 ′，5 ′-二-脱氧尿苷; 6，5 ′-环5 ′-脱氧胸苷; 6，5 '-环-5'-脱氧-5 '-羟乙基尿苷和相关中间体。5 ′-脱氧-6，5 ′-环尿苷的2 ′，3 ′-环磷酸是胰核糖核酸酶（RNase）的底物。3 '-磷酸盐是强抑制剂。这意味着核糖核酸酶识别嘧啶核苷的反式。3.碳桥嘌呤环己苷的合成：新合成了以下化合物：2 ′-脱氧-8，2 ′-乙醇腺苷; 3 ′-脱氧-8，3 ′-乙醇腺苷; 8，2 ′-乙醇腺苷; 2 ′-脱氧-8，2 ′-甲氧腺苷; 8，2 ′-甲氧腺苷; 8，2 ′-甲氧鸟苷及其α异头体。8，2 ′-环腺苷是腺苷脱氨酶的底物，而8，3 ′-化合物不是。5 '-羟基的构象对于底物与酶的结合也可能是重要的。4.测试了一些环己基糖苷的抗肿瘤（L1210）和抗病毒（HSV-1）性质。在100 μ g/ml的水平下，它们均未显示出明显的活性<micro>。

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.