Synthesis of 2-Substituted 9-Oxa-Guanines {5-Aminooxazolo 5,4-D Pyrimidin-7(6H)-Ones} and 9-Oxa-2-Thio-Xanthines{5-Mercaptooxazolo 5,4-D Pyrimidin-7(6H)-Ones}

Oxazolo[5,4-d] pyrimidines can be considered as 9-oxa-purine analogs of naturally occurring nucleic acid bases. Interest in this ring system has increased due to recent reports of biologically active derivatives. In particular, 5-aminooxazolo[5,4-d]pyrimidine-7(6H)-ones (9-oxa-guanines) have been shown to inhibit ricin. The preparation of a series of 2-substituted 5-aminooxazolo[5,4-d] pyrimidin-7(6H)-ones and related 5-thio-oxazolo[5,4-d] pyrimidines is described, including analogs suitable for further elaboration employing "click" chemistry utilizing copper-catalyzed Huisgen 1,3-dipolar cycloadditions. Two of the compounds prepared were found to inhibit ricin with IC(50) ca. 1-3 mM.