Cationic lipid exhibiting improved intracellular dynamics
a cationic lipid and intracellular kinetic technology, applied in the direction of microencapsulation, organic chemistry, microorganism ingredients, etc., can solve the problems of insufficient nucleic acid delivery efficiency achieved by the lipid membrane structure using these cationic lipids, high nucleic acid delivery efficiency of lipid membrane structures with an appropriate pka, and safety concerns, so as to influence the efficiency of endosomal escape and promote endosomal escape , the effect of high membran
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example 1
[Example 1] Synthesis of O—Ph—P3C1
[0176]While O—Ph—P3C1 was produced by the method of the formula (2), the production thereof is not limited to this method.
[0177]The formula (2)
Acid Anhydridation of Oleic Acid
[0178]Oleic acid (manufactured by NOF CORPORATION) (70.0 g, 248 mmol) was dissolved in chloroform (560 g) at room temperature, and the mixture was cooled to 10-15° C. Thereto was added dropwise a suspension of DCC (manufactured by Osaka
[0179]Synthetic Chemical Laboratories, Inc.) (25.1 g, 121 mmol) dissolved in chloroform (140 g), and the mixture was reacted at 10-25° C. for 2 hr. The reaction solution was filtered, and the filtrate was concentrated by an evaporator. The obtained is concentrate was re-dissolved in hexane (210 g), and insoluble material was removed by filtration. The obtained filtrate was concentrated by an evaporator to give oleic anhydride (64.2 g). 1H-NMR spectrum (600 MHz, CDCl3) of oleic anhydride 60.86-0.90 ppm (t, 6H), δ1.25-1.40 ppm (m, 40H), δ1.61-1.68;...
example 2
[Example 2] Synthesis of O—Ph—P4C1
[0186]O—Ph—P4C1 was synthesized by the same synthetic pathway as in Example 1.
[0187]Bis{2-[4-(hydroxymethyl)piperidyl]ethyl}disulfide (di-4PM form) 0.340 g, 0.975 mmol) synthesized by the method described in patent document 2,4-oleoyloxyphenylacetic acid (0.853 g, 2.05 mmol), and DMAP (0.0477 g, 0.390 mmol) were dissolved in chloroform (10.2 g) at room temperature. Thereto was added EDC (0.561 g, 2.93 mmol), and the mixture was reacted at 30-35° C. for 3 hr. The reaction solution was washed twice with 20% brine (6.80 g) and dehydrated using magnesium sulfate (0.340 g). Magnesium sulfate was filtered off, and the filtrate was concentrated in an evaporator to give a crude 30 product (0.900 g). The obtained crude product was subjected to column purification to give O—Ph—P4C1 (0.629 g).
[0188]1H-NMR spectrum (600 MHz, CDCl3) of O—Ph—P4C1 60.86-0.90; (t, 6H), 61.27-1.42; (m, 44H), 61.62-1.76; (m, 10H), 61.96-2.00; (m, 12H), 62.52-2.56; (m, 4H), 62.64-2.67...
example 3
[Example 3] Synthesis of O—Ph—P4C2
[0189]O—Ph—P4C2 was synthesized by the same synthetic pathway as in Example 1.
[0190]Bis{2-[4-(2-hydroxyethyl)piperidyl]ethyl}disulfide (di-4PE form) (0.350 g, 0.929 mmol) synthesized by the method described in patent document 2,4-oleoyloxyphenylacetic acid (0.813 g, 1.95 mmol), and DMAP (0.0454 g, 0.372 mmol) were dissolved in chloroform (10.5 g) at room temperature. Thereto was added EDC (0.534 g, 2.79 mmol), and the mixture was is reacted at 30-35° C. for 4 hr. The reaction solution was washed twice with 20% brine (7.00 g) and dehydrated using magnesium sulfate (0.350 g). Magnesium sulfate was filtered off, and the filtrate was concentrated in an evaporator to give a crude product (1.10 g). The obtained crude product was subjected to column purification to give O—Ph—P4C2 (0.722 g).
[0191]1H-NMR spectrum (600 MHz, CDCl3) of O—Ph—P4C2 60.86-0.90; (t, 6H), 61.22-1.42; (m, 46H), 61.54-1.76; (m, 12H), 61.94-2.03; (m, 12H), 62.52-2.56; (m, 4H), 62.62-2.6...
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