AKIRA Matsuda Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (90157313)
AKIHIKO Nomura Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (10001041)
KIYOMI Tsuchida Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 教務職員 (60088862)
HIDEO Inoue Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (80088856)
KAZUNOBU Miura Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (70001980)
|Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1986: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1985: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1984: ¥5,800,000 (Direct Cost: ¥5,800,000)
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.