鸟嘌呤核苷-3′,5′-环磷酸衍生物的合成及生物活性研究

本文报道用三价磷试剂与保护的鸟嘌呤核苷反应,经碘氧化生成鸟嘌呤核苷-3′,5′-环磷酸酯和磷酰胺,并对它们的生物活性做了初步研究,N~2-二甲胺基甲烯基-2′-叔丁基二甲基硅基鸟嘌呤核苷-3′,5′-环磷酸酯和磷酰胺对小鼠肝癌腹水细胞的DNA和RNA合成有一定的抑制作用。N~2-二甲胺基甲烯基鸟嘌呤核苷-3′,5′’-环磷酸丁酯的两个磷原子构型不同的异构体可激活腺苷酸环化酶,使大鼠成骨肉瘸细胞株ROS 17/2.8的cAMP水平增高。

SYNTHESIS AND BIOLOGICAL ACTIVITY OF DERIVATIVES OF GUANOSINE 3',5'-CYCLIC PHOSPHATE

Methyl, n-butyl 2'-TBDMS-N~2-DMF-guanosine 3', 5'-cyclic phosphate and 2'-TBDMS-N~2-DMF-guanosine 3', 5'-cyclic diethyl-phosphoramidate were synthesized by reation of protected guanosine with trivalent phosphorus reagents in the presence of tetrazole followed by oxidation. The reaction occurred stereospecifically.Protected guanosine 3', 5'-cyclic phosphotriesters and N, N'-diethylphosphoramidate were shown to have inhibitary activity on the synthesisof DNA and RNA in mouse liver tumor cell. Diastereoisomers of n-butyl N~2-substituted guanosine 3', 5'-cyclic phosphate have been shown to activate adenylate cyclase in vitro.