6-Alkynylpurines bearing electronacceptor substituents: Preparation, reactivity in cycloaddition reactions and cytostatic activity
- 16 December 2011
- journal article
- Published by Institute of Organic Chemistry & Biochemistry in Collection of Czechoslovak Chemical Communications
- Vol. 76 (12), 1487-1527
- https://doi.org/10.1135/cccc2011176
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 (IC50 = 2.6–15 μM), while the cycloadducts were inactive.Keywords
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