Statistical Optimization Applied to Simultaneous Determination of Maprotiline, Desipramine, and Moclobemide by Capillary Zone Electrophoresis

Summary. A method of Capillary Zone Electrophoresis (CZE) for separation of three most-frequently prescribed antidepressants in the market: maprotiline, desipramine, and moclobemide was developed. The proposed method is fully validated for a ternary laboratory mixture but it is also suitable for individual determination of the investigated components in pharmaceutical dosage forms. Since the preliminary investigations did not show complete separation because of close migration time of desipramine and maprotiline, a complete set, 2³ experimental design was applied. All the factors that affect separation as well as their mutual interactions were investigated. Voltage, temperature of capillary and the pH of phosphate buffer were independent variables or factors to be investigated in two levels. Applying response surface methodology, from experimental points the appropriate graphs were constructed and optimal chromatographic conditions for the separation were defined. The optimum conditions were: running voltage of 20 kV, phosphate buffer (pH = 2.35), temperature 25°C, and UV detection at 200 nm. An uncoated (fused silica) capillary (50 μm i.d.) with a total length of 50 cm and a distance of 47 cm between the injection and detection points was used.     

Diels-alder reactions with 2-(Arylsulfinyl)-1,4-benzoquinones: effect of aryl substitution on reactivity, chemoselectivity, and pi-facial diastereoselectivity

Diels-Alder reactions of (SS)-2-(2'-methoxynaphthylsulfinyl)-1, 4-benzoquinone (1b), 2-(p-methoxyphenylsulfinyl)-1,4-benzoquinone (1c), and 2-(p-nitrophenylsulfinyl)-1,4-benzoquinone (1d) with cyclopentadiene are reported. These cycloadditions allowed the highly chemo- and stereoselective formation of both diastereoisomeric endo-adducts resulting from reaction on the unsubstituted double bond C(5)-C(6) of quinones working under thermal and Eu(fod)(3)- or BF(3).OEt(2)-catalyzed conditions. The synthesis of endo-adduct [4aS,5S,8R,8aR,SS]-9d resulting from cycloaddition on the substituted C(2)-C(3) double bond was achieved in a chemo- and diastereoselective way from quinone 1d in the presence of ZnBr(2). The reactivity and selectivity of the process proved to be dependent on the electron density of the arylsulfinyl group.     

High stereocontrol in aldol reaction with ketones: enantioselective synthesis of beta-hydroxy gamma-ketoesters by ester enolate aldol reactions with 2-acyl-2-alkyl-1,3-dithiane 1-oxides

The asymmetric aldol reaction of 1,2-diketones, masked as nonracemic 2-acyl dithiane oxides, with lithium enolates derived from several esters and lactones, proceeds with a high degree of stereocontrol at both carbonyl and enolate prochiral centers, the stereocontrol mainly determined by the configuration of the sulfoxide sulfur atom. The sense of induced stereochemistry observed for ester enolates is different from that seen for lactone enolates. Hydrolysis of the dithiane oxide units of the major diastereoisomerically pure aldol products affords enantiomerically pure tertiary alpha-substituted beta-hydroxy-gamma-ketoesters.