PH sensitive phospholipid molecule and preparation method as well as application thereof

A phospholipid and molecular technology, applied in the field of biomedicine, can solve the problems of complex synthesis, inconvenient detection, poor acid response, etc., and achieve the effect of simple operation, high stability and mild process conditions

Active Publication Date: 2016-04-06
EAST CHINA NORMAL UNIV +1
View PDF3 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] One of the purposes of the present invention is to provide a novel pH-sensitive phospholipid molecule with pentaerythritol as a skeleton, the pH-sensitive phospholipid molecule is an acid-sensitive phospholipid molecule, to solve the problem of complex synthesis in the prior art, inconvenient detection, and the response to acid Bad question

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • PH sensitive phospholipid molecule and preparation method as well as application thereof
  • PH sensitive phospholipid molecule and preparation method as well as application thereof
  • PH sensitive phospholipid molecule and preparation method as well as application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] The synthesis of embodiment 1 compound III

[0069]

[0070] Dissolve 1.2g (6.6mmol) of the compound represented by formula (II) in 18mL of DMF, add 1.82g of potassium carbonate (13.2mmol) and 1.28g (10.6mmol) of allyl bromide, and heat to about 60°C under nitrogen protection Reaction 3h. DMF was distilled off under reduced pressure, then extracted with ethyl acetate, washed with saturated ammonium chloride, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=2:1) ​​to obtain 1.1 g of a light yellow solid compound represented by formula (III), with a yield of 75.34%.

[0071] 1 HNMR (400MHz, CDCl 3 )δ10.36(s,1H),6.10(s,2H),6.09–6.00(m,1H),5.44(dd,J=17.3,1.4Hz,1H),5.35(dd,J=10.5,1.2Hz ,1H), 4.61(d,J=5.4Hz,2H),3.88(s,6H).

Embodiment 2

[0072] The synthesis of embodiment 2 compound IV

[0073]

[0074] 1.0g (4.5mmol) of the compound represented by formula (III), 6.13g (45.1mmol) of pentaerythritol, 5g of molecular sieves, 80mg (0.42mmol) of p-toluenesulfonic acid monohydrate were dissolved in 25mL of DMF, under the protection of nitrogen, the temperature was raised to about 60°C, Reaction 15h. DMF was distilled off under reduced pressure, and 10 mL of saturated NaHCO was added 3 Solution, 5-10mL of water, stirred for 30min, filtered with suction, dried the filter cake, and beat with EA:PE=2:1 to obtain 1.4g of the compound represented by formula (IV) as a white solid, with a yield of 91.50%.

[0075] 1 HNMR(400MHz,DMSO)δ6.19(s,2H),6.04(ddd,J=22.4,10.5,5.3Hz,1H),5.72(s,1H),5.41(dd,J=17.3,1.4Hz,1H ),5.27(dd,J=10.5Hz,1.2Hz,1H),4.58(d,J=5.2Hz,2H),4.46(m,2H),3.84-3.76(m,4H),3.72(s,6H ),3.59(d,J=11.2Hz,2H),3.20(s,2H).

Embodiment 3

[0076] The preparation of embodiment 3 compound 5

[0077]

[0078] 1.4g (4.1mmol) compound shown in formula (IV), capric acid 1.77g (10.3mmol), 4-dimethylaminopyridine 0.1g (0.8mmol), be dissolved in 35mL dichloromethane, under ice bath, batchwise Add 2.12g (10.3mmol) N,N'-dicyclohexylcarbodiimide, after the addition is complete, react at room temperature for 2.5h. The solid was removed by suction filtration, the filtrate was washed with saturated ammonium chloride solution, saturated sodium bicarbonate solution, saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=10:1→6:1→5:1, a small amount of triethylamine was added to the developing solvent) to obtain 2.5 g of the compound shown in formula (5) as a white solid. The yield was 93.83%.

[0079] 1 HNMR (400MHz, CDCl 3 )δ6.12(s,2H),6.08–5.98(m,1H),5.96(s,1...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
particle sizeaaaaaaaaaa
particle diameteraaaaaaaaaa
particle diameteraaaaaaaaaa
Login to view more

Abstract

The invention discloses a novel pH sensitive phospholipid molecule taking pentaerythritol as a skeleton, and a preparation method as well as application of the phospholipid molecule, and particularly relates to the novel pH sensitive phospholipid molecule shown as a formula (I). The phospholipid molecule can form a liposome in an aqueous solvent; acetal bond is sensitive to an acid environment, so that the liposome can be quickly dissociated under an acidic condition, and thus an aim of quickly releasing load is achieved. The phospholipid molecule has the characteristics of ultraviolet absorption, easy detection and no cytotoxicity to tumor cell, and has great potential in becoming an acid sensitive medicinal material; the formula (I) is shown in the description.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a pH-sensitive phospholipid molecule with pentaerythritol as a skeleton and a preparation method and application thereof. Background technique [0002] Phospholipids are amphiphilic molecules with a hydrophilic nitrogen or phosphorus head at one end and a long hydrophobic (oleophilic) hydrocarbon chain at the other end. According to the main chain structure of phospholipids, it can be divided into phosphoglycerides and sphingomyelins, that is, the phospholipids composed of glycerol are called glycerophospholipids, and the phospholipids composed of sphingosine are called sphingomyelins. Phospholipids are important components of biological membranes and the main constituents of liposome bilayers, and can be used as emulsifiers and surfactants. [0003] Liposome is a spherical closed vesicle formed by phospholipids dispersed in water, encapsulating a part of the water phase. It...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/655A61K9/127A61K47/24
CPCA61K9/127A61K47/24C07F9/6552
Inventor 罗宇常淑媛罗恬许程桃王思洋
Owner EAST CHINA NORMAL UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap