SYNTHESIS, STRUCTURE, AND REACTIVITY OF ADENOSINE CYCLIC 3',5'-PHOSPHATE BENZYL TRIESTERS
SYNTHESIS, STRUCTURE, AND REACTIVITY OF ADENOSINE CYCLIC 3',5'-PHOSPHATE BENZYL TRIESTERS
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DOI：
10.1021/jm00217a008
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发表时间：
1977-01-01
影响因子：
7.3
通讯作者：
SCHLAEGER, EJ
中科院分区：
文献类型：
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作者：
ENGELS, J;SCHLAEGER, EJ
用不同的重氮烷烃（R = H, CH3, C6H5, o-NO2C6H4,p-CH3C6H4）处理游离酸，合成了一系列环[c]AMP三酯。得到的非对映异构体混合物被分离成轴向组分和赤道组分。研究了化合物的水解和光降解性邻硝基苯基酯的光解作用。然后测试所有化合物激活cAMP依赖性蛋白激酶的能力，并作为cAMP磷酸二酯酶的底物，结果显示对任何一种酶几乎没有影响。在一项生物试验中，苯三酯能够渗透到c6大鼠胶质瘤细胞中，并诱导细胞形状的典型形态学改变，这是已知的高水平cAMP细胞。cAMP的苯三酯似乎是有用的衍生物，可以有效地和特异性地转化为母体核苷酸。生物活性磷酸二酯的苄基衍生物可为生物学和药理学研究提供有用的工具。
A series of triesters of cyclic[c]AMP was synthetized by treatment of free acid with various diazoalkanes (R = H, CH3, C6H5, o-NO2C6H4,p-CH3C6H4). The resulting diastereomeric mixtures were separated into their axial and equatorial components. Hydrolysis of the compounds and photolysis of the photolabile o-nitrobenzyl ester were examined. All compounds were then tested for their ability to activate the cAMP-dependent protein kinase and serve as a substrate for the cAMP phosphodiesterase showing almost no effect on either enzyme. In a biological assay the benzyl triesters were able to penetrate into C 6 rat glioma cells and induce the typical morphological alteration of the cell shape known for high cellular levels of cAMP. The benzyl triesters of cAMP appear to be useful derivatives which can be efficiently and specifically converted to the parent nucleotide. Benzyl derivatives of biologically active phosphodiesters may provide a useful tool for study in biology and pharmacology.