Uses
5-Iodo-2'-deoxycytidine is used in the construction of DNA oligomers to enable structural studies and photoactivated cross-linking. It is used in the synthesis of other modified nucleosides, such as 5-ethynylferrocenyl-2-deoxycytidine used in semiconductor electrodes and 10-(2-deoxyβ-D-ribofuranosyl)pyrimido[4,5:4,5]pyrimido[1,6-a]indole-6,9(7H)-dione (dCPPI).
Synthesis
General procedure for the synthesis of 4-amino-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one (dC) from 4-amino-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-iodopyrimidin-2(1H)-one: in a flame-dried round-bottom flask In a flame-dried round-bottom flask, 10.0 g of dC (44.0 mmol, 1.0 eq.), 7.70 g of iodine (26.4 mmol, 0.6 eq.) and 11.4 g of mCPBA (70%, 46.2 mmol, 1.05 eq.) were dissolved in 120 mL of DMF. The reaction mixture was stirred at room temperature for 2 h and subsequently evaporated to dryness (a small amount of DMF residue was acceptable in subsequent column chromatography). Purification by column chromatography (eluent ratio: DCM/MeOH/H2O/NH3 190:10:0.6:0.6 → 90:10:0.6:0.6) afforded 9.71 g (63% yield) of target compound 1 as an orange solid. The product characterization data were as follows: 1H NMR (400 MHz, CDCl3/MeOD) δ (ppm) = 8.46 (s, 1H), 6.13 (t, 3J = 6.0 Hz, 1H), 4.34 (dt, 3J = 4.7, 6.3 Hz, 1H), 3.93 (dt, 3J = 3.0, 4.3 Hz, 1H), 3.84 (dd. 3J = 3.0, 2J = 12.1 Hz, 1H), 3.72 (dd, 3J = 3.2, 2J = 12.1 Hz, 1H), 2.39 (dd, 3J = 4.8, 6.3, 2J = 13.7 Hz, 1H), 2.20-2.09 (m, 1H).13C NMR (101 MHz, MeOD) δ (ppm) = 163.9, 153.9, 150.9, 89.5, 88.3, 71.5, 62.2, 56.2, 42.5. HRMS (ESI+) Calculated C9H13IN3O4+ [M+H]+: 353.9945, Measured: 353.9944. Melting point range: 133-135°C (Decomposition). IR (ATR). 3191 (w), 1718 (m), 1642 (s), 1286 (m), 1087 (s), 957 (s), 750 (m).
References
[1] Organic Letters, 2010, vol. 12, # 24, p. 5671 - 5673
[2] Patent: WO2012/62907, 2012, A1. Location in patent: Page/Page column 13; 14
[3] Patent: US2013/237697, 2013, A1. Location in patent: Paragraph 0052-0055
[4] Synthesis, 2009, # 23, p. 3957 - 3962
[5] Patent: US2012/178919, 2012, A1. Location in patent: Page/Page column 4
