Pergamon S0040-4020(96)00289-X Tetrahedron, Vol. 52, No. 19, pp. 6759-6780, 1996 Copyright © 1996 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0040-4020/96 $15.00 + 0.00 Transformations of Thiopyrimidine and Thiopurine Nucleosides Following Oxidation with Dimethyldioxirane. Raffaele Saladino,* Enrico Mincione, Claudia Crestini, and Maurizio Mezzetti DipartimentoAgrochimico Agrobiologico Universit~ degli studi di Viterbo "La Tuscia", via San Camillode LeUis,01100 Viterbo,Italy. Abstract: A general and convenient method for the synthesis of several pyrimidine and purine nucleosides by selective oxidation of thionucleosideswith dimethyidioxiraneis reported. Thioketo moieties in the C-4 position of the pyrimidine ring, and in the C-6, and C-8 positionsof the purine ring are the domain of oxidative nucleophilic substitution.Thioketo moieties in the C-2 position of both parine and pyrimidine ringsare the domainof desulfarization or formation of disulfides. Copyright © 1996 Elsevier Science Ltd In the chemislry of nucleosides general methods for the synthesis of biologically important derivatives starting from thiopyrimidine and thiopurine nucleosides have been developed. 1 Moreover, chemical transformations of thiopyrimidine and thiopurine nucleosides have been proposed as key reactions in a number of biochemical processes including metabolic pathways2 and structural modifications of transfer-ribonucleic acids (t-RNAs). 3 Among the various synthetic methods reported,4 only the direct nucleophilic substitution of the mercapto moiety with alcohols or amines in a sealed tube at high temperature5 has became a standard procedure. 6 In the presence of C-5 substituents on the thiopyrimidine ring, or in the presence of heavily hindered amines, 7 the conversion shows varying degrees of success as well as limitations due to side reactions.4b In the course of our studies on the chemistry of nucleic acid components 8 we have employed the oxidation of 2-thiouracils,9 pyrimidine-2-thione, 10 4-thiopyrimidine, and 6-thiopurine nucleosides, 11 with ozone for site-specific introduction of alkoxyl or alkylamino groups at C-2 uracil and pyrimidine or C-6 purine residues, respectively. The method is quite general and affords cytosine and adenosine nucleosides routinely in acceptable yields, even if, the ozonolysis of the C-5,6 uracil double bond to give 5-substituted hydantoin derivatives becames an undesirable side reaction in the presence of C-5 electron-releasing substituents. 11,12,13 Recently, we have also shown that dimethyldioxirane (indicated only as DMDO in the continuation of the paper), a powerful and selective oxidant with performs under strictly neutral conditions, 14 reacts under mild reaction conditions with the C-5,6 double bond of pyrimidine nucleosides 15,16 and with the C,N-7,8 double bond of caffeine and purine nucleosides 17 to give C-5,6 pyrimidine epoxidation or C-8 purine hydroxylation. Preliminary studies on the oxidation of 4-thiopyrimidine and 6-thiopurine nucleosides 18,19 with DMDO have 6759