Pyridine → O6-Methyl-2'-deoxyguanosine

Reaktionsgleichung

[C@@H:1]1([N:9]2[C:19]3[N:18]=[C:16]([NH2:17])[NH:15][C:13](=[O:14])[C:12]=3[N:11]=[CH:10]2)[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.N1C=C[CH:23]=[CH:22][CH:21]=1>>[CH:22]([O:14][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:19]=2[N:18]=[C:16]([NH2:17])[N:15]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1)([CH3:23])[CH3:21].[CH3:21][O:14][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:19]=2[N:18]=[C:16]([NH2:17])[N:15]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.[CH2:21]([O:14][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:19]=2[N:18]=[C:16]([NH2:17])[N:15]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1)[CH3:22]

Komponenten

Edukt 2

HCID 1049Pyridine

HCID 135398592Deoxyguanosine

Produkt 3

HCID 73317O6-Methyl-2'-deoxyguanosine

HCID 99549O6-Ethyldeoxyguanosine

HCID 158855Guanosine, 2'-deoxy-6-O-(1-methylethyl)-

Versuchsvorschrift

O6 -Methyldeoxyguanosine, O6 -ethyldeoxyguanosine and O6 -isopropyldeoxyguanosine are synthesized according to the published procedure of Fathi et al. (Tetrahedron Lett. 31:319-322, 1990). Trifluoroacetic anyhydride (2.3 mL, 16 mmol) is added to a cooled (0° C.) solution of 2'-deoxyguanosine (2 mmol, available from Sigma Chemical Company) in pyridine (10 mL). After 10 minutes, the appropriate alkoxide (4.3 g) in 300 mL of the appropriate alcohol (sodium methoxide in methanol for O6 -methyldeoxyguanosine, sodium ethoxide in ethanol for O6 -ethyldeoxyguanosine, sodium isopropoxide in isopropyl alcohol for O6 -isopropyldeoxyguanosine) is added dropwise and the reaction mixture is stirred for 24 hours (or 60 hours for the ethyl derivative and two days for the isopropyl derivative). The reaction is quenched with a solution of pyridinium hydrochloride (made from 12 mL pyridine and 4 mL of hydrochloric acid) and the excess acid destroyed with sodium bicarbonate (2 g). The mixture is then evaporated to dryness, resuspended in water and purified on a DYNAMAX (Rainin Instrument Co.) reversed-phase HPLC column using a gradient of 2-5% acetontrile in water over 45 minutes to yield O6 -methyldeoxyguanosine, O6 -ethyldeoxyguanosine or O6 -isopropyledeoxyguanosine, depending upon the particular alkoxide used above.