6-Alkynylpurines bearing electronacceptor substituents: Preparation, reactivity in cycloaddition reactions and cytostatic activity

M. Křováček, H. Dvořáková, I. Votruba, I. Císařová, D. Dvořák
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引用次数: 3

Abstract

While direct Sonogashira coupling of 6-halopurines with methyl propiolate and with propargyl aldehyde was not successful, the corresponding orthoester and propargyl aldehyde diethylacetal reacted smoothly. Such prepared orthoester was then converted to the desired methylester by methanolysis, the acetal was too stable to be hydrolyzed. The obtained 6-ethynylpurines, bearing orthoester, acetal, methoxycarbonyl and for comparison also the phenyl substituent on the ethynyl group, were subjected to the cycloaddition reaction with cyclopentadiene, diazomethane and phenylazide. Electron deficient alkynylpurines were considerably more reactive in this reaction compared to the not activated phenylethynyl derivative. The prepared alkynylpurines exhibited medium cytostatic activity (IC 50 = 2.6–15 μM), while the cycloadducts were inactive.
含电子受体取代基的6-炔基嘌呤:制备、环加成反应活性和细胞抑制活性
虽然6-卤嘌呤与丙酸甲酯和丙炔醛的Sonogashira直接偶联不成功,但相应的正酯和丙炔醛二乙基缩醛反应顺利。所制备的正构酯通过甲醇水解转化为所需的甲基酯,缩醛太稳定而不能水解。与环戊二烯、重氮甲烷和苯基肼进行环加成反应,得到6-乙基嘌呤,含正酯、缩醛、甲氧羰基和乙基上的苯基取代基。与未激活的苯乙基衍生物相比,缺电子炔基嘌呤在该反应中具有明显的活性。所制备的炔基嘌呤具有中等的细胞抑制活性(ic50 = 2.6 ~ 15 μM),而环加合物无活性。
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