65% |
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Synthesis of DSDMA and DODMA: (0248) DSDMA and DODMA were synthesized using the respective alkyl bromides with methodology derived from that of a DOTMA precursor (Feigner et al, PNAS USA, 84, 7413-7417 (1987)). 3-(Dimethylamino)-1,2-propanediol (714 mg, 6 mmol) and 95percent sodium hydride (NaH, 1.26 g, 50 mmol) were stirred in benzene (30 mL) under argon for 30 minutes. The correct (either oleyl or stearyl) alkyl bromide (5.0 g, 15 mmol) was added and the reaction refluxed under argon for 18 hours. The reaction mixture was then cooled in an ice bath while quenching via the slow addition of ethanol. Following dilution with a further 150 mL of benzene, the mixture was washed with distilled water (2×150 mL) and brine (150 mL), using ethanol (20 mL) to aid phase separation if necessary. The organic phase was dried over magnesium sulphate and evaporated. The crude product was purified on a silica gel (Kiesel Gel 60) column eluted with chloroform containing 0-5percent methanol. Column fractions were analyzed by thin layer chromatography (TLC) (silica gel, chloroform/methanol 9:1 v/v, visualized with molybdate) and fractions containing pure product (Rf=0.5) were pooled and concentrated. The product was decolorized by stirring for 30 minutes in a suspension of activated charcoal (1 g) in ethanol (75 mL) at 60° C. The charcoal was removed by filtration through Celite, and the ethanol solution concentrated to typically yield 2.4 g (65percent) of pure product. 1H-NMR (DSDMA): deltaH 3.65-3.32 (m, 7H, OCH, 3×OCH2), 2.45-2.31 (m, 2H, NCH2), 2.27 (s, 6H, 2×NCH3), 1.61-1.45 (m, 4H, OCH2CH2), 1.40-1.17 (m, 60H, Hstearyl), 0.86 (t, 6H, CH2CH3). 1H-NMR (DODMA): deltaH 5.4-5.27 (m, 4H, 2×CH?CH), 3.65-3.35 (m, 7H, OCH, 3×OCH2), 2.47-2.33 (m, 2H, NCH2), 2.28 (s, 6H, 2×NCH3), 2.06-1.94 (m, 8H, 4×CH2CH?CH), 1.61-1.50 (m, 4H, OCH2CH2), 1.38-1.20 (m, 48H, Holeyl), 0.88 (t, 6H, CH2CH3). |