Hydrochloric Acid → (2R,3S)-1-(Phenanthrene-2-carbonyl)-piperazine-2,3-dicarboxylic acid

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Reaction Conditions

Reaction Steps

2-Carboxyphenanthrene (2 g, 0.009 mol) was suspended in dry benzene (50 ml) and heated under reflux in the presence of thionyl chloride (5 ml) for 5 hr. The solvent was removed and the corresponding acid chloride was used without further purification. Piperazine-2,3-dicarboxylic acid (0.508 g, 0.003 mol) was dissolved in a 0.991 M aqueous sodium hydroxide solution (9.4 ml, 0.009 mol), dioxane (10 ml) was added and the solution was cooled to 0° C. A solution of the acid chloride (0.84 g, 0.0035 mol) in dioxane (10 ml) was added to the reaction mixture. The reaction was warmed to room temperature and stirred for 2-3 hr. The reaction mixture was acidified to pH 2-3 with aqueous HCl. The solid was filtered, dissolved in dioxane/ H2O (50:50) and bound to an ion exchange resin (Dowex-AG50 H+ form) chromatography column. It was eluted with dioxane/H2O (50:50) until organic impurities are removed. The column was eluted with 10% aqueous pyridine and the ninhydrin fractions were combined. The solvent was removed and the solid was crystallised from H2O to give a white solid (0.128 g, 12%). m.p.=218.1-221.7 ° C. (dec.); 1H NMR (300 MHz, NaOD/ D2O) 7.7-8.8 (m, 9H, Ar), 5.6 (d, 0.5H, CH—CO2H, JAB=2.6Hz), 4.8 (d, 0.5H, CH—CO2H, JAB=2.6Hz), 4.4 (d, 0.4H, CH—CO2H, JAB=12.0Hz), 3.6 (d, 0.4H, CH—CO2H, JAB=12.0Hz), 2.5-3.8 (m, 4H, N—CH2CH2—NH); Elemental analysis calculated for C21,H18N2O5. 2.3H2O C:60.07, H:5.44, N:6.67. Found C:60.06, H:5.38, N: 6.85. The cis-isomerism was confirmed by COSEY 1H NMR.

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