Abstract:

(Chemical Equation Presented) 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. 1 × 106 s-1 and is highly stereoselective affording only the (5′S)-diastereomer. © 2007 American Chemical Society.

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