Reaktionsschritte
The malonic acid (73) (5.48 g, 18.0 mmol) was refluxed in pyridine/water (1:1) (20 mL) until no diacid remained (SiO2 :EtOH-EtOAc (1:1) +1% AcOH; rf 0.26). The reaction mixture was cooled, diluted with water (50 mL), and acidified with 10% sulphuric acid (50 mL). The resulting solution was left at 0° C. overnight to crystallize. The brown solid was filtered off and dried to yield 2-acetamido-3-(3-indolyl)butanoic acid isomer A (74A) (1.30 g, 28%); δ H (300M Hz; d6 -DMSO), 1.32 (3H, J 9 Hz, CH3), 1.84 (3H, s, CHH3CO), 3.46-3.55 (1H, m, indCH(CH3)-), 4.58-4.67 (1H, m, CH(COOH)NHAc), 6.93-7.19 (3H, m), 7.34 (1H, d, J 8 Hz, amide NH), 7.54 (1H, J 8 Hz, indole 7-H), 8.04 (1H, d, J 9 Hz, indole-4H), 10.81 (1H brs, indole NH), ca 12.4 (vbrs, CO2H). The filtrate was extracted with ethyl acetate (4×100 mL). The ethyl acetate extracts were combined and washed with water (2×50 mL) then extracted with 10% sodium hydrogen carbonate (2×100 mL). The sodium hydrogen carbonate extract was acidified with 4N sulphuric acid then extracted with ethyl acetate (2×75 mL). The ethyl acetate solution was washed with water (2×25 mL) then evaporated to dryness to give a beige foam, 2-acetamido-3-(3-indolyl)butanoic acid isomer B (74B) (2.17 g, 46%); δ H (300M Hz, d6 -DMSO), 1.32 (3H, d, J 7 Hz, CH3), 1.84 (3H, s, CH3CO), 3.50 (1H, M, ind CH(CH3)-), 4.66 (1H, m, CH(COOH)NHAc), 6.93-719 (3H, m), 7.34 (1H, d, J 8 Hz, amide NH), 7.63 (1H, d, J 8 Hz, indole 7-H), 7.84 (1H, d, J 9 Hz, indole 4-H), 10.83 (1H, s, indole NH), ca 12.5 (vbrs, CO2H).
