Synthesis of 3,7,8‐15N3‐N1‐(β‐D‐erythro‐pentofuranosyl)‐5‐guanidinohydantoin

Abstract

Abstract3,7,8‐15N3‐N1‐(β‐D‐erythro‐pentofuranosyl)‐5‐guanidinohydantoin was synthesized from the oxidation of 1,7,NH2‐15N3‐8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine with 2 equivalents of Ir(IV) in pH 4.5 potassium phosphate buffer. The synthesis of 1,7,NH2‐15N3‐8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine started with bromination of 1,7,NH2‐15N3‐2′‐deoxyguanosine. The resulting 1,7,NH2‐15N3‐8‐bromo‐7,8‐dihydro‐2′‐deoxyguanosine reacted with sodium benzyloxide to afford 1,7,NH2‐15N3‐8‐benzyloxy‐7,8‐dihydro‐2′‐deoxyguanosine. Subsequent catalytic transfer hydrogenation of 1,7,NH2‐15N3‐8‐benzyloxy‐7,8‐dihydro‐2′‐deoxyguanosine with cyclohexene and 10% Pd/C yielded 1,7,NH2‐15N3‐8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine. Purification of 3,7,8‐15N3‐N1‐(β‐D‐erythro‐pentofuranosyl)‐5‐guanidinohydantoin was first carried out on a C18 column and the product was further purified on a graphite column. ESI‐MS was used to confirm the identity and to determine the isotopic purity of all the labeled compounds. The isotopic purity of 3,7,8‐15N3‐N1‐(β‐D‐erythro‐pentofuranosyl)‐5‐guanidinohydantoin was 99.4 atom% based on LC‐MS measurements. Copyright © 2003 John Wiley & Sons, Ltd.