Collect. Czech. Chem. Commun. 1990, 55, 1801-1811

Synthesis of 3'-azido-2',3'-dideoxy-6-methyluridine, 2',3'-dideoxy-6-methyluridine and 2',3'-dideoxy-2',3'-didehydro-6-methyluridine

Hubert Hřebabeckýa, Antonín Holýa and Eric De Clercqb

a Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6, Czechoslovakia
b Rega Institut, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium


3'-Azido-2',3'-dideoxy-6-methyluridine (VIb) was prepared, together with its N3-isomer VIIb, by opening the 2,3'-bond in anhydronucleoside III with lithium azide in dimethylformamide and subsequent detritylation. The anhydro derivative III was synthesized from 2'-deoxy-6-methyluridine (I) by tritylation, mesylation and closure of the 2,3'-anhydro bond with 1,8-diazabicyclo[5.4.0]undec-7-ene. Dideoxy derivative XV was prepared by Barton deoxygenation of phenoxythiocarbonyl derivative IX followed by desilylation with tetrabutylammonium fluoride. Reduction of bis(phenoxythiocarbonyl) derivative XV with tributyltin hydride afforded 2',3'-dideoxy-2',3'-didehydro derivative XVI. The compound XV was obtained from arabinosyl derivative XIII which arises, along with 5,6-dihydro derivative XIV, by reaction of anhydronucleoside XII with lithium hydroxide in aqueous methanol. Desilylation of compound XVI with tetrabutylammonium fluoride resulted in quantitative removal of 6-methyluracil.