Collect. Czech. Chem. Commun.
2011, 76, 1487-1527
https://doi.org/10.1135/cccc2011176
Published online 2011-12-16 14:15:30
6-Alkynylpurines bearing electronacceptor substituents: Preparation, reactivity in cycloaddition reactions and cytostatic activity
Martin Křováčeka, Hana Dvořákováb, Ivan Votrubac, Ivana Císařovád and Dalimil Dvořáka,*
a Department of Organic Chemistry, Institute of Chemical Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic
b Laboratory of NMR Spectroscopy, Institute of Chemical Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic
c Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
d Department of Inorganic Chemistry, Charles University in Prague, Hlavova 2030, 128 40 Prague 2, Czech Republic
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: Alkynylpurines; Cytotoxicity; Cycloaddition reactions.
References: 18 live references.
