Synthetic and oxidative studies on 8-(arylamino)-2'-deoxyguanosine and -guanosine derivatives.
Facile aerial oxidation is a general feature of guanine ribo- and 2'-deoxyribonucleosides that are substituted at the 8-position by an aminoaryl group. In previous work, it had been suggested that two of the major oxidation products are a pair of diastereomers having a spiro structure. These were presumed to be related by a chiral difference at the spiro carbon atom. The pattern of the oxidative process involves a contraction of the pyrimidine ring. It was thought to be analogous to that suggested by other investigators for the oxidation of uric acid, but for which no really definitive evidence had been presented. We have been able now to isolate in a crystalline state one of the diastereomers produced by the aerial oxidation of 8-phenylaminoguanosine under alkaline conditions. Analysis by X-ray diffraction has now confirmed the type of spiro structure promulgated previously. These findings also imply that spiro compounds are likely to be produced during the aerial oxidation of any 8-arylaminoguanine nucleoside or 2'-deoxynucleoside. In addition, this work adds considerable weight to the results of Poje and Sokolic-Maravic who proposed that a spiro intermediate is produced during the aerial oxidation of uric acid (12,13). However, they found this compound to be unstable to base, in contrast to the arylaminoguanine oxidation products. In the course of the above work we showed that the 8-arylamino derivatives of guanosine can be converted by the Barton deoxygenation method to the corresponding 2'-deoxyribonucleosides. This makes available a number of the latter compounds, which are not easily prepared by other methods.
Johnson
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Pharmacological Sciences Department, State University of New York at Stony Brook.
Huang
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Yu
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D018736:DNA Adducts / Q000138:chemical synthesis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
D018736:DNA Adducts; D006151:Guanosine; D003849:Deoxyguanosine