Synthesis of [1,3, NH2-15N3] (5′S)-8,5′-cyclo-2′-deoxyguanosine†

To facilitate NMR studies and low-level detection in biological samples by mass spectrometry, [1,3, NH2-15N3] (5′S)-8,5′-cyclo-2′-deoxyguanosine was synthesized from imidazole-4,5-dicarboxylic acid in 21 steps. The three 15N isotopes were introduced during the chemo-enzymatic preparation of [1,3, NH2-15N3]-2′-deoxyguanosine using an established procedure. The 15N-labeled 2′-deoxyguanosine was converted to a 5′-phenylthio derivative, which allowed the 8-5′ covalent bond formation via photochemical homolytic cleavage of the C–SPh bond. SeO2 oxidation of C-5′ followed by sodium borohydride reduction and deprotection gave the desired product in good yield. The isotopic purity of the [1,3, NH2-15N3] (5′S)-8,5′-cyclo-2′-deoxyguanosine was in excess of 99.94 atom% based on liquid chromatography–mass spectrometry measurements. Copyright © 2013 John Wiley & Sons, Ltd.