Molecules 2015, 20
9401
MPEG5000-Val-HCPT (4c): 1H-NMR (DMSO-d6) δ (ppm): 8.69 (s, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.19
(d, J = 8.8 Hz, 1H), 7.91 (s, ,1H), 7.65 (d, J = 7.6 Hz, 1H), 7.35 (s, 1H), 6.54 (s, 1H), 5.43 (s, 2H), 5.30
(s, 2H), 4.29–4.32 (m, 1H), 4.17–4.20 (m, 1H), 4.03–4.06 (m, 1H), 3.44–3.68 (s, mPEG), 3.24 (s, 3H),
2.14–2.18 (m, 1H), 1.86–1.89 (m, 2H), 0.98–1.01 (m, 6H), 0.89 (t, J =7.2 Hz, 3H).
1
HCPT-Val-PEG2000-Val-HCPT (4d): H-NMR (DMSO-d6) δ (ppm): 8.68 (s, 2H), 8.43 (d, J = 8.0 Hz,
2H), 8.19 (d, J = 9.2 Hz, 2H), 7.91 (d, J = 2.4 Hz, 2H), 7.63–7.66 (dd, J = 9.2, 2.4 Hz, 2H), 7.35 (s,
2H), 6.53 (s, 2H), 5.43 (s, 4H), 5.30 (s, 4H), 4.28–4.32 (m, 2H), 4.17–4.20 (m, 2H), 4.02–4.06
(m, 2H), 3.45–3.66 (s, PEG), 2.13–2.18 (m, 2H), 1.84–1.91 (m, 4H), 0.98–1.01 (m,12H), 0.89 (t,
J = 7.2 Hz, 6H).
HCPT-Val-PEG20000-Val-HCPT (4e): 1H-NMR (DMSO-d6) δ (ppm): 8.70 (s, 2H), 8.45 (d, J = 7.2 Hz,
2H), 8.20 (d, J = 8.8 Hz, 2H), 7.93 (s, 2H), 7.65–7.67 (d, J = 7.6, 2H), 7.37 (s, 2H), 6.55 (s, 2H), 5.44
(s, 4H), 5.32 (s, 4H), 4.21–4.31 (m, 4H), 4.06–4.08 (m, 2H), 3.52–3.69 (s, PEG), 2.17–2.18 (m, 2H),
1.89 (m, 4H), 1.01 (m, 12H), 0.83 (t, J = 7.2Hz, 6H).
1
HCPT-Val-PEG300-Val-HCPT (4f): H-NMR (DMSO-d6) δ (ppm): 8.66 (s, 2H), 8.44 (d, J = 8.0 Hz,
2H), 8.17 (d, J = 8.8 Hz, 2H), 7.90 (s, 2H), 7.63 (d, J = 8.4, 2H), 7.34 (s, 2H), 6.53 (s, 2H), 5.43 (s,
4H), 5.28 (s, 4H), 4.18–4.33 (m, 4H), 4.03–4.07 (m, 2H), 3.50–3.65 (s, PEG), 2.16–2.17 (m, 2H),
1.85–1.91 (m, 4H), 0.98–1.00 (m, 12H), 0.89 (t, J = 7.2 Hz, 6H).
MPEG2000 (4-nitrophenyl) carbonate (1b): Methoxypolyethylene glycol 2000 (mPEG2000, 3.0 g,
1.5 mmol) was dissolved in anhydrous CH2Cl2 (15 mL). Triethylamine (4.2 mL, 30.0 mmol) and
4-nitrophenyl chloroformate (1.2 g, 6.0 mmol) were added at 0 °C and the mixture was stirred at room
temperature for 3 h. The mixture was concentrated under vacuum, purified by column chromatography
(CH2Cl2/CH3OH, 25:1, v/v) and recrystallized from ethyl ether to afford compound 1b (2.6 g, 80%
yield). 1H-NMR (DMSO-d6) δ (ppm): 8.32(d, J = 9.2 Hz, 2H), 7.57(d, J = 9.2 Hz, 2H), 4.38–4.36 (m,
2H), 3.71–3.42 (s, mPEG), 3.24 (s, 3H).
mPEG2000-OCO-HCPT (5): To a stirred solution of HCPT (150.0 mg, 0.4 mmol) in anhydrous DMF
were added triethylamine (0.24 mL, 1.7 mmol) and compound 1b (0.6 g, 0.3 mmol). The reaction
mixture was stirred at 60 °C for 45 min, diluted with water, and extracted with CH2Cl2. The organic
layer was combined, dried with anhydrous sodium sulfate, concentrated under vacuum, purified by
column chromatography (CH2Cl2/CH3OH, 25:1, v/v) and recrystallized with ethyl ether to give
compound 5 (350.0 g, 55% yield). 1H-NMR (DMSO-d6) δ (ppm): 8.70 (s, 1H), 8.24 (d, J = 9.2 Hz, 1H),
8.05 (d, J = 2.4 Hz, 1H), 7.78–7.81 (dd, J = 9.2, 2.4 Hz, 2H), 7.36 (s, 1H), 6.55 (s, 1H), 5.44 (s, 2H),
5.31 (s, 2H), 4.39 (t, 2H), 3.75–3.41 (s, mPEG), 3.24 (s, 3H), 1.82–1.93 (m, 2H), 0.89 (t, J = 7.2 Hz, 3H).
MPEG2000 4-methylbenzenesulfonate (7): mPEG2000 (3.0 g, 1.5 mmol) was dissolved in anhydrous
CH2Cl2 (15.0 mL). Triethylamine (4.2 mL, 29.8 mmol) and 4-methoxybenzenesulfonyl chloride (0.9 g,
5.1 mmol) were added at 0 °C. The mixture was heated to reflux for 5 h, diluted with CH2Cl2, and
washed with 1 N HCl and brine. The organic layer was dried with anhydrous sodium sulfate,
concentrated under vacuum and purified by recrystallization with ethyl ether to give compound 7