Preparation method of disulfide bond-containing dual-response functional molecule and hydrogel microsphere and application thereof
A hydrogel microsphere, dual response technology, applied in the field of large-scale cell culture, can solve the problems of low porosity and inapplicability to large-scale cell culture
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Embodiment 1
[0086] Synthesis of ANB-1
[0087]
[0088] (1) Synthesis of compound a2
[0089] Compound a1 (1.5g, 0.01mol) was dissolved in 100mL of tetrahydrofuran, 10mL of 1.68mol / L NaOH solution and p-toluenesulfonyl chloride (1.9g, 0.01mol) were added under stirring condition, and reacted at room temperature for 9h. After the reaction, the pH was adjusted to be neutral, the organic solvent in the system was removed by rotary evaporation as much as possible, and an appropriate amount of ethyl acetate and deionized water were added for extraction twice. The organic phase was dried with anhydrous sodium sulfate and the solvent was concentrated, and purified by silica gel column to obtain compound a2.
[0090] The physical parameters of compound a2 are: 1 H NMR (400MHz, DMSO-d6), δ(ppm): 7.74(d, 2H), 7.35(d, 2H), 3.83(t, J=6.24Hz, 2H), 3.21(t, J=6.35Hz, 2H),2.81(m,4H),2.42(s,3H). 13 C NMR (101MHz, DMSO), δ (ppm): 147.53, 144.67, 131.52, 125.56, 62.54, 61.96, 41.83, 36.88, 22.47. MS ...
Embodiment 2
[0110] The synthetic route of NNB-1:
[0111]
[0112] (1) Synthesis of a10
[0113] Cystamine hydrochloride compound a9 (15g, 0.1mol) was added to a 500mL single-necked round-bottomed flask, and 150mL of methanol was added for dissolution. BOC anhydride (di-tert-butyl dicarbonate) (21g, 0.1mol) and triethylamine ( 43mL, 0.3mol) was dissolved in 100mL of methanol, and slowly added dropwise to the flask under stirring at room temperature, and reacted with stirring at room temperature for 0.5 hours after the dropwise addition was completed. After the reaction, the methanol was spin-dried to obtain a white solid crude product, which was added with 1M NaHPO 4 The solution was 200 mL, and the aqueous phase was washed with 2×100 mL ether. The aqueous phase was adjusted to pH=9 with 1M NaOH, extracted with 2×100 mL ethyl acetate, the organic phase was separated, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain compound a10 a...
Embodiment 3
[0125] The synthetic route of NAB-1:
[0126]
[0127] The synthesis method of NAB-1 refers to the synthesis method of NNB-1. First, the intermediate a14 is prepared according to the third step in the synthesis method of NNB-1, and then the compound NAB-1 is obtained by deprotection according to the fourth step.
[0128] The physical parameters of NAB-1 are: 1 H NMR(400MHz,DMSO-d6),δ(ppm):6.65-6.57(m,2H),6.40-6.34(m,2H),4.45(s,2H),3.51(t,2H),3.12-2.81 (m,6H). 13 C NMR (101MHz, DMSO), δ (ppm): 167.63, 158.27, 136.18, 122.35, 114.73, 62.68, 39.11, 38.28, 36.74, 35.77. MS (ESI): m / z: Calcd.for C 12 h 17 N 5 o 2 S 2 Na + [M+Na] + :350.1Found:350.1.
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