HCID 67175249, compound → 2'-C-Methylcytidine

Participants

Reaction Steps

Walton et al. described the synthesis of 2′-C-methyladenosine from 2-C-methyl-D-ribono-lactone (Walton et al., J. Am. Chem. Soc., 88(19):4524-5 (1966)). In this case, the lactone was converted into its 2,3,5-tri-O-benzoyl derivative, and then reduced with bis(3-methyl-2-butyl)borane to provide an anomeric mixture of 2,3,5-tri-O-benzoyl-2-C-methyl-D-ribofuranose (Id.). Attempts at separating the anomeric mixture both on acid-washed alumina and on silica gel resulted in rearrangement to 1,3,5-tetra-O-benzoyl-2-C-methyl-α-D-ribofuranose (Id.). In order to avoid rearrangement, the additional steps of treating the mixed anomers with benzoyl chloride in pyridine to obtain 1,2,3,5-tetra-O-benzoyl-2-C-methyl-(α)/(β)-D-ribofuranose, and of isolating the final product by chromatography were needed (Id.). Later Walton et al. described the synthesis of 2′-C-methyl-5-fluorocytidine, 2′-C-methyl-5-fluorouridine, and 2′- and 3′-C-methylcytidine via the Hilbert-Johnson reaction (Walton et al., Antiviral Nucleosides 12:306-309 (1969)). However, unexpectedly large amounts of O-glycoside formed when 2′-C-methylcytidine was synthesized from N-acetylcytosine-mercury, and mercury itself is a toxic reagent whose avoidance is desirable (Id.). In both synthetic procedures described by Walton et al., the final product yield was only about 11%.

Provenance & Evidence