Phosphorus, Sulfur, and Silicon, 178:1199–1209, 2003 Copyright C  Taylor & Francis Inc. ISSN: 1042-6507 print DOI: 10.1080/10426500390200477 SOME 2 0 -MODIFIED 4 0 -THIONUCLEOSIDES VIA SULFUR PARTICIPATION AND SYNTHESIS OF THIO-AZT FROM 4 0 -THIOFURANOID 1,2-GLYCAL Najim A. Al-Masoudi, a Yaseen A. Al-Soud, b and Ahmed I. Khodair c Universit ¨ at Konstanz, Konstanz, Germany; a University of Al al-Bayt, Al-Mafraq, Jordan; b and Tanta University (Kafr-El-Sheikh), Tanta, Egypt c (Received September 20, 2002; accepted October 31, 2002) ThioAZT 14 was synthesized in eight steps from D-arabinose derivative 4 via the new thiofuranoid 1,2-glycal, 5-O-Acetyl-1,2,4-trideoxy-1,4- epithio-3-O- p-toluenesulfonyl-D-threo-pent-1-enitol (8). Ribosylation of the thiosugar 6 with thymine afforded regioselectively the nucleo- side 16. Treatment of 16 with sodium azide in hot DMF gave, after spontaneous intramolecular displacment, the 2 0 -azido-xylo derivative 18, which furnished the free nucleoside 19 on treatment with methano- lic ammonia. Similarly, treatment of 16 with sodium ethylthiolate in boiling methanol led to inversion in configuration and gave, after sev- eral intramolecular displacments, via the sulfur participation, the 2 0 ,3 0 - diethylthiolate-ribo derivative 23. Deblocking of 23 with methanolic ammonia afforded the free nuclaoside 24. Keywords: Antiviral agents; ribosylation; sulfur paricipation; thioAZT; 4 0 -thiofuraniod glycal There has been increasing interest in recent years in the synthesis of nucleosides from sugar precursors in which the furanose ring atom is replaced by a sulfur atom and led to promising antiviral or antitu- mor nucleosides, such as 4 0 -thiothymidine (1),4 0 -thio-2 0 deoxyxytidine (2), 1 and 4 0 -thioangustmycin C (3). 2 This interest has stimulated the synthesis of this class of nucleosides, especially those modified at We thank Miss A. Frieml and Mr. H¨ agele for the NMR experiments and the mass spectra measurements, respectively. Address correspondence to N. A. Al-Masoudi, Fakult¨ at f¨ ur Chemie, Universit ¨ at Konstanz, Postfach 5560, Konstanz, D-78457 Germany. E-mail: Najim.Al-Masoudi@uni- konstanz.de 1199