Tri-O-acetylguanosine

White Solid

2.2 mL of acetic anhydride (22 mmol) was added dropwise to a suspension of guanosine (2 g, 7.0 mmol) (dried for 2 days over P2.2 mL of acetic anhydride (22 mmol) was added dropwise to a suspension of commercially available guanosine (2 g, 7.0 mmol), triethylamine (7.7 mL, 55.2 mmol) and N, N-(dimethylamino)pyridine (92 mg, 0.75 mmol) in 27 mL of acetonitrile at 0oC. The mixture was stirred until it became homogeneous and kept an additional 1 hr at room temperature. The reaction was quenched with methanol (2.3 mL). The volume was reduced to 1/3 using a rotary evaporator and diethyl ether was added dropwise to induce precipitation of a fine white powder. The product was collected by filtration, washed with diethyl ether, and then stirred for 2 hr with acetone (30 mL) at 50 C. The filtrate produced 2.8 g (98percent) of a fine white powder.A suspension of 113 g (0.4 mol) of dry guanosine (6.1), acetic anhydride (240 mL, 2.5 mol), dry pyridine (120 mL) and dry DMF (320 mL) was heated for 3.75 hours at 75°C without allowing the temperature to exceed 80°C. The clear solution was then transferred to a 3L Erlenmyer flask and filled with 2-propanol. Upon cooling the solution to room temperature crystallization was initiated and allowed to proceed at 4°C overnight. The white solid filtrate was filtered, washed with 2-propanol and recrystallized from 2-propanol to give 6.2 (96percent). 1H NMR (300 Mhz, CDCl3) δ 8.20 (s, 1H, H-8), 6.17 (d, J= 5.41 Hz, 1 H, H-1') 5.75 (t, J= 5.39 Hz, 1H, H-2'), 5.56 (t, J = 5.0, H-3'), 4.41 (m, 3H, H-4', 5'), 2.14 (s, 3H, Ac), 2.11 (s, 3H, Ac), 2.10 (s, 3H, Ac). 13C NMR (300 MHz, CD3OD) δ 171.0, 170.3, 1702, 157.7, 154.8, 152.4, 136.7, 117.7, 85.5, 80.4, 73.0, 71.3, 64.0, 31.3, 21.2, 21.0.Guanosine 1 (11.3 g, 40 mmol) and N, N-dimethylaminopyridine (366 mg, 3 mmol, 0.07 equiv) were dissolved in 500 mL acetonitrile. After addition of triethylamine (22.9 mL, 158.4 mmol) and AcTo a stirred suspension of guanosine (5.0 g, 17.7 mmol) in MeCN (65 mL) was added Et3N (6.47 mL, 46.5 mmol) and DMAP (0.22 g, 1.8mmol). The resulting suspension was cooled in an ice bath prior to dropwise addition of Ac2O (5.84 mL, 61.84 mmol). Once the addition was completed, the mixture was allowed to reach room temperature and was stirred for a further 2 h. The reaction was quenched by the addition of MeOH (6.5 mL) and concentrated in vacuo to a white semi-solid precipitate which was boiled with iPrOH and filtered, leaving the product as a white solid. (5.79 g, 80percent). 1H NMR (500 MHz, DMSO-d6): δ (ppm) 10.70 (1H, s, NH); 7.91 (1H, s, H8); 6.49 (2H, s, NH2); 5.98 (1H, d, 3JH1'H2' = 6.1Hz, H1'); 5.79 (1H, t, 3JH2'H3' = 6.0 Hz, H2'); 5.50 (1H, dd, 3JH3'H4' = 4.2, H3'); 4.37 (1H, dd, 3JH5''H4' = 3.8 and 2JH5H5 =11.5 Hz, H5); 4.31 (1H, m, H4); 4.26 (1H, dd, 3JH5H4 = 5.7 Hz, H5'); 2.11 [3H, s, (CH3)3']; 2.04 [3H, s, (CH3)5']; 2.03 [3H, s, (CH3)2']. 13C NMR (125 MHz, DMSOd6): δ (ppm) 170.89 [(CO)5']; 170.24 [(CO)3']; 170.07 [(CO)2']; 157.46 (C6); 154.75 (C2); 151.95 (C4); 136.45 (C8); 117.74 (C5); 85.35 (C1'); 80.40 (C4'); 72.93 (C2'); 71.18 (C3'); 63.92 (C5'); 21.34 [(CH3)5']; 21.20 [(CH3)3'] and 21.01 [(CH3)2'].Guanosine (6) 8.40 g (29.7 mmol) and 0.2 g of dimethylaminopyridine were suspended in a mixture of ethyldimethylamine 8.8 g (120 mmol), acetic anhydride 10.2 g (100 mmol) and acetonitrile 100 mL. The reaction mixture was stirred for 60 minutes at room temperature until the solution becomes clear. Methanol was added to the reaction mixture and the solvents were removed under vacuum. The product was recrystallized from isopropanol, washed with acetone and dried to give 6a as pure product. Yield 9.6 g (79percent)Step A: Guanosine (1) (90 g, 387.9 mmol) was dissolved in dry pyridine and DMF (95.4 mL) followed by the addition of acetic anhydride (191.15 mL, 2420.0 mmol) and the reaction mixture was stirred at 75 °C for 4.15 h. The resultant clear solution was mixed with 2-propanol and maintained at 4 °C for overnight to afford white solid which was recrystallized from 2-propanol, 10percent methanol in chloroform to afforded compound2in 70percent yield.Spectral data is consistent with the literature.General procedure: Nucleoside/nucleotide (2; 100 mM) and N-acetyl imidazole (1a;10 equiv) were dissolved in water (pH 8; adjusted with 4 MNaOH). The solution was incubated at r.t. for 4 h, and NMR spectra were periodically acquired. The product was purified byreverse-phase (C18) flash coumn chromatography (eluted at pH4 with 100 mM NH4HCO2/MeCN = 98:2 to 80:20). The fractions containing 5 were lyophilised to yield a white powder.

Molecular Weight:409.35
XLogP3:-0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:10
Rotatable Bond Count:8
Exact Mass:409.12336258
Monoisotopic Mass:409.12336258
Topological Polar Surface Area:173
Heavy Atom Count:29
Complexity:743
Undefined Atom Stereocenter Count:4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes