8-位取代嘌呤衍生物的合成与机理研究

以9 -苄基嘌呤和碘代丁二酰亚胺(NIS)为原料,研究开发了8 碘9 -苄基嘌呤合成的新方法。较佳反应条件为:反应溶剂THF,反应温度70 ℃,n(9 苄基嘌呤)∶n(NIS)=1∶2.5,反应时间48 h。在此条件下,产品收率达87%以上。另外,以(Ph3P)2PdCl2为催化剂,对8 碘9 苄基嘌呤与有机基锡试剂RSnBu3 之间的Stille 偶合反应进行了研究。得到较佳反应条件为:反应温度80~100 ℃,n(8 碘9 苄基嘌呤)∶n(RSnBu3)∶n((Ph3P)2PdCl2)= 1 0∶1 2∶0.05,反应时间24 h。在上述条件下,产品收率为91%(R=乙烯基)、86%(R=2 噻吩基)、90%(R=2 呋喃基)、80%(R=苯乙炔基)和42%(R=苯基)。采用1 H NMR、13 C NMR、MS、碳氢相关谱(HETCOR)和远程碳氢相关谱(Long Range HETCOR)等分析手段对所得产物结构进行了表征,证明其结构正确,并对两步反应的机理进行了探讨。

Studies on Synthesis and Reaction Mechanism of 8-Substituted-purine Derivatives

Iodo-9-benzylpurine was synthesized by using 9-benzylpurine and N-iodosuccinimide(NIS) as raw materials. Under the optimum reaction conditions of reaction temperature 70 ℃, n(9-benzylpurine):n(NIS) =1.0∶2.5 and reaction time 48 h, the yield of product was over 87%. Moreover, the Stille coupling reaction between 8-iodo-9-benzylpurine and RSnBu 3(R=vinyl, 2-thienyl, 2-furyl, phenylethynyl and phenyl) was studied using (Ph 3P) 2PdCl 2 as catalyst. Under the optimum reaction conditions of reaction temperature 80~100 ℃, n(8-iodo-9-benzylpurine)∶n(RSnBu 3)∶n (Ph 3P) 2PdCl 2] = 1.0∶1.2∶0.05 and reaction time 24 h, the yield of product was 42%~91%.The product was characterized by 1H-NMR, 13C-NMR, MS, HETCOR and Long Range HETCOR and the reaction mechanism was discussed.