The first chemical synthesis of 3-methyl-ψ-uridine (5) and its 2′-deoxy analogue (9) has been achieved. ψ-Uridine was trimethylsilylated and the crude product was treated with acetyl chloride, to give the 1-acetyl derivative (3). Crude 3 was methylated with dimethoxymethyldimethylamine and then saponified, to give crystalline 5 in 82% overall yield. Treatment of 5 with 1,3-dichloro-1,1,3,3-tetraiso-propyldisiloxane afforded the 3′,5′-protected product, which was converted into the 2′-O-[(imidazol-1-yl)thiocarbonyl] derivative 7. Reduction of 7 with tributyltin hydride followed by deblocking of the product gave crystalline 2′-deoxy-3-methyl-ψ-uridine (9) in 35% yield from 5.
Bibliographical noteFunding Information:
*Nucleosides, Part 122. This investigation was supported by funds from the National Cancer Institute, U. S. Department of Health and Human Services (Grants CA-08748 and CA-24634). **On leave (1980-1982) from the Center of MoIecular and Macromolecular Studies, Polish Academy of Sciences, L.odz, Poland. ***To whom all correspondence should be addressed.
Copyright 2018 Elsevier B.V., All rights reserved.