New method for preparing (R)-1,2-di-fatty acid glycerol phosphatidyl glyceride

A fatty acid glycerol phosphatidylglycerol, a new method technology, applied in the field of medicine and chemical industry, can solve the problems of using heavy metals or highly toxic oxidants, not suitable for industrial production, complex routes, etc., achieve good optical stability, easy introduction, mild reaction Effect

Inactive Publication Date: 2016-10-05
江苏东南纳米材料有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has disadvantages such as complicated routes, lengthy steps, and the use of heavy metals or highly toxic oxidants, and is not suitable for industrial production.

Method used

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  • New method for preparing (R)-1,2-di-fatty acid glycerol phosphatidyl glyceride
  • New method for preparing (R)-1,2-di-fatty acid glycerol phosphatidyl glyceride
  • New method for preparing (R)-1,2-di-fatty acid glycerol phosphatidyl glyceride

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Effect test

Embodiment 1

[0026] Preparation of (R)-1,2-distearoyl-[(2-cyanoethoxy)-(diisopropylamino)-phosphooxy]glyceride (R=CH 3 (CH 2 ) 16 )(method one)

[0027] Under argon protection, (S)-1,2-glyceryl stearate (0.62 g, 1 mmol) was dissolved in 10 mL of anhydrous dichloromethane, and 1 mL of diisopropylethylamine was added. At 0°C, 2-cyanoethyldiisopropylphosphoramidate chloride (0.43 mL, 2 mmol) was added dropwise, and the mixture was allowed to react overnight at room temperature. Add 10 mL of saturated aqueous sodium bicarbonate solution to terminate the reaction, extract with dichloromethane, dry the organic layer over anhydrous sodium sulfate, concentrate, and recrystallize the crude product from ethyl acetate-petroleum ether to obtain 0.62 g of (R)-1,2-dihard Fatty acyl-[(2-cyanoethoxy)-(diisopropylamino)-phosphooxy]glycerides, yield 75%.

Embodiment 2

[0029] Preparation of (R)-1,2-distearoyl-[(2-cyanoethoxy)-(diisopropylamino)-phosphooxy]glyceride (R=CH 3 (CH 2 ) 16 )(Method Two)

[0030] Under argon protection, (S)-1,2-glyceryl stearate (0.62g, 1 mmol) was dissolved in 10 mL of anhydrous dichloromethane, and 5-ethylthiotetrazolium (0.13g, 1 mmol), bis(diisopropylamino)(2-cyanoethoxy)phosphine (0.24 g, 1 mmol) was added dropwise, and heated to reflux to react overnight. Add 10 mL of saturated aqueous sodium bicarbonate solution to terminate the reaction, extract with dichloromethane, dry the organic layer over anhydrous sodium sulfate, concentrate and recrystallize the crude product from ethyl acetate-petroleum ether to obtain 0.57 g of (R)-1,2-distearyl Acyl-[(2-cyanoethoxy)-(diisopropylamino)-phosphoryloxy]glycerides, yield 69%.

Embodiment 3

[0032] (R)-1,2-Distearoyl-[(2-cyanoethoxy)-(2,2-dimethyl-1,3-dioxo-4-yl)methoxy-]phospholipid Preparation of acylglycerides (R = CH 3 (CH 2 ) 16 )

[0033] (R)-1,2-distearoyl-[(2-cyanoethoxy)-(diisopropylamino)-phosphoryloxy]glyceride (0.82 g, 1 mmol) in 10 mL of anhydrous acetonitrile, Then 15 mL of anhydrous acetonitrile solution of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane (180 μL, 1.5 mmol) and 2.5% tetrazole (5 mL) was added dropwise into the above solution and stirred at room temperature for 1 hour. Concentrate to dryness, add 0.1 M iodine tetrahydrofuran-water-pyridine (9:1:0.1) mixed solution to the concentrate, stir and react for 1 hour, then concentrate to dryness, add chloroform, then use sodium sulfite The aqueous solution and saturated brine were washed, the organic layer was anhydrous sodium sulfate, concentrated and directly used in the next reaction.

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Abstract

The invention discloses a preparing method for di-fatty acid glycerol phosphatidyl glyceride. The preparing method includes the steps that (S)-1,2-fatty glyceride serves as a raw material, and is reacted with 2-cyano ethyl diisopropyl chloro -amidophosphoric acid or di-(diisopropyl amino) (2-cyano ethyoxyl) phosphine and 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolame in sequence, then phosphate ester is generated under the condition of iodine oxidation, finally all protecting groups are removed under the ammonia water condition and the weak acid condition, and the (R)-1,2-di-fatty acid glycerol phosphatidyl glyceride is obtained. According to the method, the raw materials are low in cost and easy to obtain, the reaction conditions are mild, the steps are simple, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine and chemical industry, and in particular relates to a preparation method of (R)-1,2-difatty acid glycerol phosphatidylglyceride. Background technique [0002] Phospholipids are an important part of biological membranes. The two long hydrocarbon chains they contain are lipophilic, and the phosphate radicals they contain are hydrophilic, so that they can form closed bilayers in aqueous media and can be used as lipids. The material is used in the pharmaceutical industry. In particular, (R)-1,2-difatty acid glycerol phosphatidylglycerides have high purity, good stability, and stronger antioxidant capacity than natural phospholipids, and are very suitable for preparing liposomes. It is an indispensable and ideal additive excipient in body drug preparations. [0003] At present, there are few reports on the synthesis of (R)-1,2-difatty acid glycerol phosphatidylglycerides. CN103864840 obtains (S)-1,2...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/09
CPCY02P20/55
Inventor 吉民王冬冬李锐顾惠龙
Owner 江苏东南纳米材料有限公司
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