Thymidine → HCID 67704911, Verbindung

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

2-Amino-6-n-propoxy-9H-purine was prepared by displacement of the chlorine group on 2-amino-6-chloropurine (Aldrich Chemical Company) by propanol (Aldrich Chemical Company) in the presence of sodium hydride. 2-Amino-6-n-propoxy-9H-purine (0.50 g, 2.6 mmoles) was dissolved in dimethylformamide (5 ml, DMF) and dimethylsulphoxide (5 ml, DMSO). 3'-Deoxy-3'-fluorothymidine (0.76 g, 3.1 mmoles) and 30 ml 10 mM potassium phosphate buffer, pH 6.8, containing 0.04% potassium azide were added. Purified purine nucleoside phosphorylase (7,500 I.U.) and thymidine phosphorylase (3750 I.U.) adsorbed onto 5 ml DEAE-cellulose resin were added to the reaction mixture and the suspension stirred at 37° C. After 24 days, the reaction was filtered and the filtrate applied to a series of coupled columns. The initial column contained AG1-X2 (OH-form, 2.5×10 cm) while the second column contained Amberlite XAD-2 resin (2.5×20 cm). After sample application, the columns were washed with water (500 ml) and the product eluted with methanol. Product-containing fractions were then flash chromatographed down a silica gel column (4.8×20 cm) using dichloromethane:methanol (95:5) as eluant. Solvent was evaporated in vacuo and lyophilisation yielded 0.46 g of 2-amino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-propoxy-9H-purine (56%): mp 128° C.;

Herkunft & Nachweise