Independent generation of C5'-nucleosidyl radicals in thymidine and 2'-deoxyguanosine.
The synthesis of the C5' tert-butyl ketone of thymidine 1a and 2'-deoxyguanosine 2 is achieved by reaction of 5'-C-cyano derivatives with tert-butyl lithium followed by acid hydrolysis. The 5'R configuration is assigned by X-ray crystal structure determination of an opportunely protected derivative of 1a. The (5'S)-isomers of both nucleosides are not stable, and a complete decomposition occurs in the reaction medium. The photochemistry of 1a and 2 effectively produced the thymidin-5'-yl radical and the 2'-deoxyguanosin-5'-yl radical, respectively. In the thymidine system, the C5' radical is fully quenched in the presence of a physiological concentration of thiols. In the 2'-deoxyguanosine system, the C5' radical undergoes intramolecular attack onto the C8-N7 double bond of guanine leading ultimately to the 5',8-cyclo-2'-deoxyguanosine derivative. The cyclization of the 2'-deoxyguanosin-5'-yl radical occurs with a rate constant of ca. 1x10(6) s-1 and is highly stereoselective affording only the (5'S)-diastereomer.
Manetto
Antonio
A
ISOF, Consiglio Nazionale delle Ricerche Via P. Gobetti 101, 40129 Bologna, Italy.
Georganakis
Dimitris
D
Leondiadis
Leondios
L
Gimisis
Thanasis
T
Mayer
Peter
P
Carell
Thomas
T
Chatgilialoglu
Chryssostomos
C
D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000138:chemical synthesis / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010782:Photolysis; D013936:Thymidine / Q000138:chemical synthesis / Q000737:chemistry*
D005609:Free Radicals; D007659:Ketones; D003849:Deoxyguanosine; D013936:Thymidine