Synthesis of bicyclic pyrimidine derivatives as ATP analogues.
Synthesis of bicyclic pyrimidine derivatives as ATP analogues.
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DOI：
10.1021/jo015647w
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发表时间：
2001-07
期刊：
影响因子：
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通讯作者：
G. Makara;William Ewing;Yao Ma;E. Wintner
中科院分区：
文献类型：
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作者：
G. Makara;William Ewing;Yao Ma;E. Wintner
报道了一种以嘌呤依赖蛋白为靶点的双环嘧啶衍生物的高效通用固相合成方法。关键中间体4，6-二取代-5-氨基嘧啶的合成涉及在三相环境中使用1，1 '-二辛基紫精还原相应的硝基衍生物。温和的还原条件使得能够使用任何酸不稳定的固体载体以及宽范围的组合取代基，从而使得能够合成高度多样化的双环嘧啶的大文库。替代还原条件与氯化锡（II）和结构反应性的研究进行了讨论。
A highly efficient and general solid-phase synthesis of bicyclic pyrimidine derivatives that target purine dependent proteins is reported. The synthesis of the key intermediate, 4,6-disubstituted-5-amino-pyrimidine, involved reduction of the corresponding nitro derivatives using 1,1'-dioctyl-viologen in a triphasic milieu. The mild reduction conditions enable the use of any acid labile solid support as well as a wide range of combinatorial substituents, thus enabling the synthesis of large libraries of highly diverse bicyclic pyrimidines. Alternative reduction conditions with tin(II) chloride and structure-reactivity studies are discussed as well.