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Purines. Part XVI
Author(s) -
Mosselhi Mosselhi A.,
Pfleiderer Wolfgang
Publication year - 2010
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201000254
Subject(s) - chemistry , xanthine , purine , acetylation , purine metabolism , stereochemistry , catalysis , base (topology) , medicinal chemistry , organic chemistry , biochemistry , enzyme , mathematics , gene , mathematical analysis
A series of N ‐substituted 8‐aminoxanthines (=8‐amino‐3,7(or 3,9)‐dihydro‐1 H ‐purine‐2,6‐diones) 8 – 16 and 34 – 37 were synthesized from the corresponding 8‐nitroxanthines 1 – 7, 30 – 33 , and 8‐(phenylazo)xanthines 17 and 18 by catalytic reduction. Another approach was derived from 6‐amino‐5‐(cyanoamino)uracils (= N ‐(6‐amino‐1,2,3,4‐tetrahydro‐2,4‐dioxopyrimidin‐5‐yl)cyanamides) 23, 24 , and 27 by base‐catalyzed cyclization yielding 25 – 28 . All 8‐aminoxanthines 8 – 29 and 34 – 37 were acetylated to the corresponding 8‐(acetylamino)xanthines 40 – 57 , and prolonged heating led to 8‐(diacetylamino)xanthines 58 and 59 . Several 8‐aminoxanthines 8 – 13 were diazotized forming 8‐diazoxanthines 60 – 64 . Coupling reactions of isolated 62 and 64 and intermediary formed 8‐diazoxanthines with 1,3‐dimethylbarbituric acid (=1,3‐dimethylpyrimidine‐2,4,6(1 H ,3 H ,5 H )‐trione; 66 ) resulted in 5‐[(xanthin‐8‐yl)diazenyl]‐1,3‐dimethylbarbituric acids=3,7(or 3,9)‐dihydro‐8‐[2‐(1,2,3,4‐tetrahydro‐1,3‐dimethyl‐2,4‐dioxopyrimidin‐5‐yl)diazenyl]‐1 H ‐purine‐2,6‐diones) 67 – 80 . The newly synthesized xanthine derivatives were characterized by the determination of their p K a values, the UV‐ and NMR spectra, as well as elemental analyses.