Trimethylsilyl triflate → Guanine

Participants

Reaction Conditions

Reaction Steps

To 5 g (17.65 mmol) of N-[6-(phenylmethoxy)-1H-purin-2-yl]-acetamide was added 150 mL of dry CH3CN and 9.60 mL (38.34 mmol) of BSA and this mixture was stirred at 80° C. for 3 h. At this time, 15.65 g (33.80 mmol) of 2-deoxy-2-[(trifluoroacetyl)amino]-β-D-glucopyranose-1,3,4,6-tetraacetate was added followed by 6.80 mL (35.30 mmol) of TMSOTf. This mixture was heated with stirring at 80° C. for 12 hours. At this time, the reaction mixture was poured into 200 mL of saturated, aqueous NaHCO3 and this mixture was extracted twice with EtOAc. The combined organic layers were washed once with H2O and brine before drying over MgSO4. The crude product was obtained by filtration and concentration of the filtrate in vacuo to a brownish foam. The glycosylation product was obtained by silica gel column chromatography eluted with 50% to 75% EtOAc / hexanes. Appropriate fractions were collected and further purified by normal phase preparative HPLC eluting prepacked silica cartridges with 50% EtOAc/hexanes. In this manner, 1.75 g (15% yield) of the desired product, N-[6-(phenylmethoxy)-9-[3,4,6-tris-O-acetyl-2-deoxy-2-[(trifluoroacetyl)amino]-β-D-glucopyranosyl]-1H-purin-2-yl]acetamide, was isolated. 1H NMR: (CDCl3): guanine H-8 8.42 (s, 1H), anomeric H-1 6.19 (d, 1H), benzyl methylene 5.62 (m, 2H), N-acetamide methyl 2.30 (s, 3H). FAB-MS: m/z 667 for (M+1))+.

Provenance & Evidence