New syntheses of 2′-C-methylnucleosides starting from d-glucose and d-ribose

Synthesis of 5-O-benzyl-2-C-β-fluoromethyl-1,2,3-tri-O-acetyl- D-ribofuranose

“…This transformation has been described for the related 5-O-trityl derivative. 17 The reaction was quite slow, presumably because the formaldehyde and open-chain ribose aldehyde are in low concentration. The product (15) was isolated as a pair of anomers (2:1 ratio).…”

“…The stereochemistry obtained at C-2 can be readily explained by Figure 1, in which the formaldehyde preferentially approaches the enol syn to the adjacent hydrogen, that being the smaller substituent. The anomeric hydroxyl of 16 was protected as the pivalate ester from which a single anomer (17) was obtained by recrystallisation. Heating 17 with tetrabutylammonium fluoride in tetrahydrofuran failed to yield any 18, which was perhaps not entirely unexpected given the steric hindrance and electronic deactivation by the oxygen substituents.…”

“…δ H (CDCl 3 , 400 MHz) approx. 17 values of <3 Hz and > 5Hz are typical for α-and β-anomers, respectively. The coupling constants J 3,4 were found to be 3.7 and 7.6 Hz, consistent with α-and β-stereochemistry, respectively.…”

Synthesis of (2′S)-2′-Deoxy-2′-C-methylpurine Nucleosides and Their Phosphoramidites

“…In the first one, d-glucose is conveniently transformed into the corresponding 2'-C-methylribose; then a glycosylation step with the appropriate base affords the riboside analogue. This strategy is usually lengthy and affords low yields [14]. The second type of preparation involves the addition of organometallic reagents to the 2'-keto derivative of the nucleoside, followed by deoxygenation of the resulting alcohol [15].…”

“…(2'S)-2'-Deoxy-2'-C-methylpurine Ribosides 12 and 14. To test whether the 2'-methylpurine ribosides have any biological activity, we prepared (2'S)-2'-deoxy-2'-Cmethyladenosine (12) and (2'S)-2'-methyl-2'-C-deoxyinosine (14) from the common intermediate 8a via the reactions depicted in Scheme 3. Treatment of 8a with an ammonia solution in THF at 908 under pressure gave compound 9.…”