| 15.8% |
Stage #1: 9,10-anthracene dicarboxylic acid With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; O‐(1H‐benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 1h;
Stage #2: D-Phe-Gly-OMe In N,N-dimethyl-formamide for 240h;
Stage #3: In N,N-dimethyl-formamide for 104h; |
2, Ant-(CO-Gly-Phe-OMe)2:
9,10-anthracenedicarboxyl acid (251.8mg, 0.95mmol), HOBt (271.8mg, 2.01mmol), TBTU (644.3g, 2.01mmol) and DIPEA (1.4mL, 8mmol) were stirred at room temperature in DMF (20mL). After 1h, H-Gly-Phe-OMe (720mg, 2.14mmol) was added to the reaction mixture and stirring was continued for 6 day (approximately 140h). Another batch of HOBt, TBTU, DIPEA and H-Gly-Phe-OMe was added twice to the mixture. One after stirring for 3 days (approximately 64h) and another 2 days (40h) later. Then H2O (250mL) was added to the reaction mixture and the compound was extracted with ethyl acetate (3×300mL). Volume was reduced to ∼100mL on rotary evaporator and washed with NaHCO3 (sat., aq.), dried over Na2SO4, filtered and twice purified with flash chromatography on a prepacked silica column using a 40% → 80% ethyl acetate gradient in hexane, resulting in mono and bis derivate mixture. 150mg of obtained mixture was dissolved in ethyl acetate (150mL) and left in the refrigerator (4°C) overnight. Volume was then reduced to ∼20ml and left in the refrigerator. Precipitation occurred and the next day liquid was decanted and the precipitate was washed with hexane (2×5 mL) and dried in vacuum. Yield: 104.7mg (0.15mmol, 15.8%). (0011) 1H NMR (CDCl3, 300.13MHz) δ/ppm: 3.10 (2H, dd, J1=13.9Hz, J2=5.8Hz, β1), 3.16 (2H, dd, J1=13.9Hz, J2=5.7Hz, β2), 3.72 (6H, s, Me), 4.02-4.26 (∼4H, m, α1+EtAc), 4.85 (2H, dd, J1=5.8Hz, J2=5.7Hz, α), 6.66 (2H,d, J=7.7Hz, NH2), 7.0 (2H, t, J=8.0, NH1), 7.10-7.32 (m, under peak of solvent, Phe), 7.46 (4H, m, H2, broad), 8.00 (4H, m, H1, broad); 13C NMR (CDCl3, 75.47MHz) δ/ppm: 38.0 (β), 43.4 (α1), 52.6 (Me), 53.7 (α), 125.5 (1), 127.1 (2), 127.4 (p-Phe), 127.5 (9A), 128.8 (o-Phe), 129.5 (m-Phe), 133.1 (9), 135.9 (i-Phe), 168.3 (C1A), 169.9 (C2A), 171.8 (C1E); IR (KBr) ν/cm-1: 3297 (sharp, medium; ν N-HPhe), 3239 (weak expanded, weak; ν N-HGly), 3063 (sharp, weak; ν C-HPhe), 3032 (sharp, weak; ν C-Hanthr.), 2942 (sharp, weak; νas C-H(CH3)), 2920 (shoulder, weak; νas C-H(CH2)), 1764, 1749 (sharp, medium; ν C=Oester), 1680 (sharp, strong; ν C=Oamide-Phe), 1637 (expanded, strong; ν C=Oamide-Gly), 1568 (shoulder), 1545 (weak expanded, strong; amid II ν C-N, δ -N-H), 1521 (shoulder); ESI-MS m/z: 123, 288.2, 316.2, 341.2, 359.2, 381.2, 526.4, 554.4, 582.4, 703.1 ([M+H]+), 714.5, 725.1 ([M+Na]+), 739.4, 799.3, 825, 849.3, 1054.8,1065.7, 1076.8, 1127.8; UV/VIS λ/nm (ε/dm3 mol-1 cm-1): 259 (1.57×105), 352 (8.42×103), 370 (1.30×104), 389 (1.25×104). |
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