Synthesis of the Hilbert-Johnson glycosylation products by other methods

Abstract

2-Deoxyribofuranosylations of 4-methoxy-2(l //)-pyrimidinone (I) and its 5-methyl derivative II were performed by the silylation and mercuri procedures leading exclusively to anomeric nucleosides, and the steric course was examined. Ribofuranosylation and glucopyranosylation when performed according to the mercuri process, lead to mixtures of N 1- and 02-glycosyl derivatives; the steric course is explained by involvement of the subsequent O -> N transglycosyla tion. In connection with investigations on utilization of the Hilbert-Johnson reaction as a complementary nucleosidation method, attention has been paid to the preparation of versatile Hilbert-Johnson products by some other procedures such as the silylation and mercuri process. In systematic investigations on the silylation method, Wittenburg1 also used 5-methyl-4-ethoxy-2(l#)-pyrimidinone, the glycosylation of which affords nucleosides in fair yields. Glycosylations of 4-alkoxy-2(lH )-pyrimidinones by the mercuri procedure were reported by other authors 2-4 . The preparation of protected l-glycosyl-4-methoxy-2(lH)-pyrimidinones was performed with the use of 4-methoxy-2(lH)-pyrimidinone (/) and its 5-methyl derivative II as the starting material. In 2-deoxyribofu ranosylations according to the silylation method, the pyrimidinones I and II were converted into the 4-methoxy-2-trimethylsilyloxypyrimidines III and IV, resp., which were treated with one equivalent of 3,5-di-0-p-to luyl-2-deoxy-D-ribofuranosyl chloride (F) in acetonitrile in the presence of mercuric acetate. Within several minutes at room temperature, the pyrimidine III afforded a 45% yield of nucleosides VI and VIII in the anomeric ratio a/P equal to 0-8. From the pyrimidine IV, the nucleosides VII and IX (anomeric ratio, 0-75) were obtained in 57% yield. In both cases, the yields of anomeric pairs are higher and the anomeric ratios are more favourable with respect to the formation of the P-anomer than in 2-deoxyribofu ranosylations of 2,4-dimethoxypyrimidines in the presence of mercuric salts5; similar results have been reported by Wittenburg 1.