Description
2''-C-Methylcytidine (2CMC) is a ribonucleoside with broad-spectrum antiviral activity. It reduces the number of viral plaques in BHK-21 cells infected with dengue type 2, reovirus type 1, West Nile, and yellow fever RNA viruses with EC
50 values of 95, 26, 80, and 75 μM, respectively. 2CMC inhibits hepatitis C virus (HCV) replication (EC
50 = 2.2 μM in a replicon assay) and protects MDBK cells from infection with bovine virus diarrhea virus (BVDV; EC
50 = 2.2 μM) and human coronavirus (HCoV; EC
50 = 90 μM). It also reduces infectious virus yield in BHK-21 cells infected with foot-and-mouth disease virus (FMDV; EC
50 = 6.4 μM) and swine vesicular disease virus (SVDV; EC
50 = 45.2 μM).
In vivo, 2CMC reduces viral shedding to undetectable levels in a mouse model of persistent norovirus infection.
Chemical Properties
White to Off-White Powder
Uses
2’-C-Methyl Cytidine (cas# 20724-73-6) is a compound useful in organic synthesis.
Biochem/physiol Actions
2′-C-Methylcytidine is a potent inhibitor of the HCV NS5B RNA polymerase. 2′-C-Methylcytidine was the first nucleoside NS5B inhibitor that showed clinical efficacy. 2′-C-Methylcytidine was found to be effective against the 17D vaccine strain of yellow fever virus YFV in cell culture.
Synthesis
Example 2: Synthesis of 2'-C-methylcytidine (4)
A methanolic solution of saturated NH3 (250 mL) was added to the compound of Example 1 (5.4 g, 8.0 mmol) and the reaction mixture was stirred overnight at room temperature. Upon completion of the reaction, the solvent was removed by rotary evaporation and the residue was purified by silica gel column chromatography with the eluent CH2Cl2/MeOH/NH3 (8.3:1.5:0.2) to afford 4-amino-1-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidin-2(1H)-one as a white solid, yield 80%.
TLC analysis (CH2Cl2/MeOH/NH3, 8.3:1.5:0.2): Rf = 0.13.
1H NMR (500 MHz, MeOD) δ: 8.13 (d, 1H, J6,5 = 7.5 Hz, H-6), 6.02 (s, 1H, H-1'), 5.89 (d, 1H, J5,6 = 7.5 Hz, H-5), 3.99-3.96 (dd, J = 1.9 Hz, 12.45 Hz, 1H, H-5'), 3.93 -3.91 (m, 1H, H-4'), 3.82-3.77 (m, 2H, H-3' and H-5''), 1.10 (s, 3H, -CH3).
13C NMR (125 MHz, MeOD) δ: 167.5 (C-4), 158.5 (C-2), 143.1 (C-6), 95.9 (C-5), 93.9 (C-1'), 83.8 (C-4'), 80.2 (C-2'), 73.7 (C-3'), 60.8 (C-5'), 20.5 (-CH3).
HRMS (ESI+) calculated value C10H15N3O5Na [M + Na]+ 280.0904, measured value 280.0901.
References
[1] Organic and Biomolecular Chemistry, 2015, vol. 13, # 18, p. 5158 - 5174
[2] Patent: WO2015/158913, 2015, A1. Location in patent: Page/Page column 37
