CN102964377A - Method for preparing natural L-alpha-glycerol phosphatidylcholine - Google Patents
Method for preparing natural L-alpha-glycerol phosphatidylcholine Download PDFInfo
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- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title abstract description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 title abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000000047 product Substances 0.000 claims abstract description 31
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 30
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- 239000002244 precipitate Substances 0.000 claims abstract description 11
- 239000006228 supernatant Substances 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims abstract description 9
- 238000001556 precipitation Methods 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- KIZQNNOULOCVDM-UHFFFAOYSA-M 2-hydroxyethyl(trimethyl)azanium;hydroxide Chemical compound [OH-].C[N+](C)(C)CCO KIZQNNOULOCVDM-UHFFFAOYSA-M 0.000 claims description 14
- 229940042880 natural phospholipid Drugs 0.000 claims description 11
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 7
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- 230000008030 elimination Effects 0.000 claims description 5
- 238000003379 elimination reaction Methods 0.000 claims description 5
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 5
- 238000001291 vacuum drying Methods 0.000 claims description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 235000010469 Glycine max Nutrition 0.000 claims description 3
- 244000068988 Glycine max Species 0.000 claims description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 210000002969 egg yolk Anatomy 0.000 claims description 3
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 0.000 abstract description 8
- 239000002904 solvent Substances 0.000 abstract description 6
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 abstract description 4
- 229940067606 lecithin Drugs 0.000 abstract description 4
- 239000000787 lecithin Substances 0.000 abstract description 4
- 235000010445 lecithin Nutrition 0.000 abstract description 4
- 239000002778 food additive Substances 0.000 abstract description 3
- 235000013376 functional food Nutrition 0.000 abstract description 3
- 230000036541 health Effects 0.000 abstract description 3
- 238000005809 transesterification reaction Methods 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 abstract 2
- 229940075419 choline hydroxide Drugs 0.000 abstract 2
- 230000020176 deacylation Effects 0.000 abstract 1
- 238000005947 deacylation reaction Methods 0.000 abstract 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 10
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 8
- 229940083466 soybean lecithin Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 239000002994 raw material Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 150000002730 mercury Chemical class 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 230000007096 poisonous effect Effects 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- RNVYQYLELCKWAN-RXMQYKEDSA-N [(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)OC[C@@H](CO)O1 RNVYQYLELCKWAN-RXMQYKEDSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- WOLYOHIQBLTAHM-UHFFFAOYSA-N 2-hydroxyethyl-dimethyl-[(oxo-lambda5-phosphanylidyne)methyl]azanium tetramethylazanium Chemical compound C[N+](C)(C)C.C[N+](C)(CCO)C#P=O WOLYOHIQBLTAHM-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- BIZAESXWKCHPME-UHFFFAOYSA-N C(C)[N+](CC)(CC)CC.P(=O)#C[N+](CCO)(C)C Chemical compound C(C)[N+](CC)(CC)CC.P(=O)#C[N+](CCO)(C)C BIZAESXWKCHPME-UHFFFAOYSA-N 0.000 description 1
- MJJLPVTVJUMSCE-UHFFFAOYSA-N CCCCC.[P] Chemical compound CCCCC.[P] MJJLPVTVJUMSCE-UHFFFAOYSA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002551 biofuel Substances 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 229960004788 choline alfoscerate Drugs 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001924 fatty-acyl group Chemical group 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- SUHOQUVVVLNYQR-MRVPVSSYSA-O glycerylphosphorylcholine Chemical compound C[N+](C)(C)CCO[P@](O)(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-O 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- PYJNAPOPMIJKJZ-UHFFFAOYSA-N phosphorylcholine chloride Chemical compound [Cl-].C[N+](C)(C)CCOP(O)(O)=O PYJNAPOPMIJKJZ-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- CQBPOPVKDNHISM-UHFFFAOYSA-N propane-1,2,3-triol;propan-2-one Chemical compound CC(C)=O.OCC(O)CO CQBPOPVKDNHISM-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
Abstract
本发明公开了一种天然L-α-甘油磷脂酰胆碱的制备方法，将已知磷脂酰胆碱含量的天然卵磷脂溶于甲基叔丁基醚，滤去不溶物后调节温度至5～55°C；在该温度条件下，按照无水低碳醇与磷脂酰胆碱摩尔比为3:1～600:1加入无水低碳醇和氢氧化胆碱，搅拌反应0.25～4个小时；倒掉上清液，将油状沉淀物用无水乙醇溶解并用甲基叔丁基醚沉淀，沉淀完全后弃上清，再反复用无水乙醇溶解并用甲基叔丁基醚沉淀2～3次，将得到的油状产物真空干燥。本发明的方法以氢氧化胆碱为催化剂，甲基叔丁基醚为溶剂，通过磷脂酰胆碱与无水低碳醇进行酯交换反应，得到GPC或以GPC为主的天然卵磷脂脱酰基物；工艺简单，反应条件温和安全，并能保障所得产物作为功能食品添加剂及医药保健品的安全性。The invention discloses a preparation method of natural L-alpha-glycerol phosphatidylcholine. The natural lecithin with known phosphatidylcholine content is dissolved in methyl tert-butyl ether, and the temperature is adjusted to 5 ~55°C; at this temperature, add anhydrous low-carbon alcohol and choline hydroxide according to the molar ratio of anhydrous low-carbon alcohol to phosphatidylcholine of 3:1-600:1, and stir for 0.25-4 hours Pour off the supernatant, dissolve the oily precipitate with absolute ethanol and precipitate with methyl tert-butyl ether, discard the supernatant after the precipitation is complete, then repeatedly dissolve with absolute ethanol and precipitate with methyl tert-butyl ether for 2 to 3 Once, the resulting oily product was dried in vacuo. The method of the present invention uses choline hydroxide as a catalyst, methyl tert-butyl ether as a solvent, and carries out transesterification reaction between phosphatidylcholine and anhydrous low-carbon alcohol to obtain GPC or natural lecithin deacylation mainly based on GPC The process is simple, the reaction conditions are mild and safe, and the safety of the obtained product as a functional food additive and medical and health product can be guaranteed.
Description
Technical field
The present invention relates to medicine, functional foodstuff industry and catalysis technical field, be specifically related to the preparation method of a kind of natural L-α-glyceryl phosphatide phatidylcholine.
Background technology
L-α-glyceryl phosphatide phatidylcholine (L-α-glycerophosphocholine is hereinafter to be referred as GPC) is the aqueous phospholipid of naturally occurring a kind of uniqueness in the human body.Studies show that GPC not only can improve different steps crowd's memory capability and cognitive ability, especially to the elderly, can effectively prevent and treat senile dementia, and the elderly's cerebral apoplexy phenomenon is had certain restraining effect; Simultaneously, it can also promote the release of human growth hormone, and teen-age height is made moderate progress, and also can effectively regulate middle-aged people's hormone balance, plays the effect of beauty treatment, delaying senility.Therefore, GPC can be widely used in medicine, healthcare products and functional foodstuff industry.
In recent years, some have occurred and contained the functional health product of GPC and other natural phospholipid deacylated tRNA base thing, but producer adopts the method for chemosynthesis to produce GPC mostly both at home and abroad.EP0486100 is by D-acetone glycerol and 2-oxygen-2-chloro-1, after the reaction of 3-diepoxy phosphorus pentane again with Trimethylamine 99 open loop condensation, the used raw material of this process is unstable, needs pressurized operation in the simultaneous reactions process, the condition harshness.EP0502357 then reacts D-acetone glycerol and Tosyl chloride to 18h first under 0 ° of C, obtain the acetone glycerol p-toluenesulfonic esters, again with the condensation reaction of phosphorylcholine tetramethyl ammonium, can obtain product GPC after the hydrolysis, although this method has been avoided the problem of pressurized operation, but still exist raw material unstable, the problem that complex process and cost are higher.The disclosed scheme of CN101544667A is after first Racemic glycidol being made the Racemic glycidol p-toluenesulfonic esters, prepare GPC with the condensation of phosphorylcholine tetraethyl-ammonium salt again, avoided the defective of raw material Racemic glycidol purifying difficulty, but the reaction process more complicated, total recovery is lower.The disclosed scheme of WO2007145476 is to utilize 2，3-epoxy-1-propanol and phosphorylcholine under the condition that Isopropylamine exists, and carries out nucleophilic addition and prepares GPC, obtained certain producing effects, but in the process material purity has been had relatively high expectations, and reaction yield is low.Usually, complex process, the yield by the synthetic GPC of chemical method low and used poisonous chemical raw material, its product to be used for food and there is very large potential safety hazard in medical aspect more.
From the natural matters such as soybean lecithin or Ovum Gallus domesticus Flavus lecithin through hydrolysis slough aliphatic side chains and obtain GPC be its as the more favourable preparation approach of Medicines and Health Product and functional food additives, compare with chemical method, side reaction is less, product is more natural.The disclosed scheme of US2864848 adopts water-soluble mercury salt to make catalyzer, and the phosphatide emulsion is prepared GPC in boiling Water Under solution, though raw material is natural, product yield is low, and separates poisonous mercury salt complex process.The disclosed scheme of EP0217765 and WO90/13552 all adopts sodium methylate as catalyzer, prepare GPC by the alcoholysis soybean lecithin, this process is higher to ingredient requirement, saponification reaction just can occur in the existence of a small amount of water, a large amount of organic solvents and water have been used in the product separation process simultaneously, both increase cost, caused again environmental pollution.Document [Chem.Phys.lipid.4.104 (1970)] has been reported the technique take tetrabutylammonium as catalyst for ester exchange reaction, although gentle than mercury salt, the residual edible safety that still affects product of 4-butyl ammonium.The disclosed scheme of CN102516292A is as catalyzer with low-boiling amine, by natural phospholipid reaction preparation GPC, reaction conditions is gentle, the time is short, product purity is high, and catalyzer can reclaim use together by distillation mode and methyl alcohol, simplified preparation technology, but low-boiling amine does not still possess the characteristic of totally nontoxic, and there be certain threat in a large amount of uses of methyl alcohol to the security of production process and product; There is production safety hidden danger in ether as solvent in this technique simultaneously.
Summary of the invention
For existing prepare take natural phosphatidyl choline as raw material that the catalyzer that exists in the GPC technique is poisonous, solvent ether uses dangerous, reactant methanol that there are the problems such as security hidden danger in technique and product.The present invention has proposed the preparation method of a kind of natural L-α-glyceryl phosphatide phatidylcholine on the basis of lot of experiments.This preparation method is take bursine as catalyzer, and methyl tertiary butyl ether carries out transesterification reaction as solvent by phosphatidylcholine and nontoxic low-carbon alcohol, obtains GPC or take GPC as main natural phospholipid deacylated tRNA base thing.
In order to achieve the above object, the present invention adopts following technical scheme:
The preparation method of a kind of natural L-α-glyceryl phosphatide phatidylcholine, concrete preparation process is as follows:
The natural phosphatidyl choline of known phosphatidylcholine content is dissolved in methyl tertiary butyl ether, adjusts the temperature to 5～55 ° of C behind the elimination insolubles; Under this temperature condition, be 3:1～600:1 according to anhydrous low-carbon alcohol and phosphatidylcholine mol ratio, add the pure and mild catalyzer bursine of anhydrous low-carbon, the consumption that makes bursine in the reaction system is every liter of 1～30mmol, stirring reaction 0.25～4 hour; Reaction is outwelled supernatant liquor after finishing; with oily throw out anhydrous alcohol solution; and precipitate with methyl tertiary butyl ether; the fully rear abandoning supernatant of precipitation; repeatedly precipitate 2～3 times with anhydrous alcohol solution and with methyl tertiary butyl ether again; the oily product that obtains is carried out vacuum-drying under the condition that Vanadium Pentoxide in FLAKES exists, namely obtain take the mixture of glyceryl phosphatide phatidylcholine as main natural phospholipid deacylated tRNA base thing.
Further, described anhydrous low-carbon alcohol adopts a kind of in methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol or the isopropylcarbinol.
Further, described natural phosphatidyl choline is from the extract of soybean, yolk or pluck, and wherein the content of phosphatidylcholine is 20%～98%.
The mixture of the natural phospholipid deacylated tRNA base thing that the present invention obtains comprises glyceryl phosphatide phatidylcholine (GPC), L-ALPHA-GPE (GPE) and glyceryl phosphatide acyl Serine (GPS); because three's character is similar; and have similar physiological function and health-care effect; when therefore being used as the additive of medicine, healthcare products and functional foodstuff in industry, the three can be combined together use.Simultaneously its content is relevant with raw material, when the phosphatidylcholine content in the natural Yelkin TTS is 80% when above, obtains the higher GPC of purity.Reaction principle of the present invention is as follows:
Wherein, R1 and R2 represent the aliphatic hydrocarbon of C13-C25; R3 represents
With
In a kind of, three kinds of materials that obtain are respectively GPC, GPE and GPS.
Beneficial effect of the present invention is as follows:
1, bursine is as the effective shift reaction of catalysis fatty acyl group of catalyzer, and the reaction times is short, mild condition; And can keep phosphoramide bond stability in the feed composition, thereby keep the peculiar structure of natural phospholipid.Simultaneously, choline is the common food additive, a small amount of residually also can not affect its safe handling even have in product.
2, used in the reaction process that toxicity is little, boiling point is high and used the methyl tertiary butyl ether of safety to be solvent, so that preparation process and product are more safe and reliable.
3, the methyl alcohol during preferred green dehydrated alcohol replacement classical inverse is answered has ensured further that as reactant products therefrom is used for the security of healthcare products and medicine.
Embodiment
The preparation method of natural L-α of the present invention-glyceryl phosphatide phatidylcholine, concrete preparation process is as follows:
The natural phosphatidyl choline of known phosphatidylcholine content is dissolved in methyl tertiary butyl ether, adjusts the temperature to 5～55 ° of C behind the elimination insolubles; Under this temperature condition, be 3:1～600:1 according to anhydrous low-carbon alcohol and phosphatidylcholine mol ratio, add the pure and mild catalyzer bursine of anhydrous low-carbon, the consumption that makes bursine in the reaction system is every liter of 1～30mmol, stirring reaction 0.25～4 hour; Reaction is outwelled supernatant liquor after finishing; with oily throw out anhydrous alcohol solution; and precipitate with methyl tertiary butyl ether; the fully rear abandoning supernatant of precipitation; repeatedly precipitate 2～3 times with anhydrous alcohol solution and with methyl tertiary butyl ether again; the oily product that obtains is carried out vacuum-drying under the condition that Vanadium Pentoxide in FLAKES exists, namely obtain take the mixture of glyceryl phosphatide phatidylcholine as main natural phospholipid deacylated tRNA base thing.
Even described catalyzer bursine has a small amount of residual its safe handling that also can not affect in product, its free choline is additive commonly used in the food.
Described methyl tertiary butyl ether toxicity is little, boiling point is high and use safety, and the methyl tertiary butyl ether among the present invention is available other energy dissolving lecithin and safety low-poison solvents also.
Described dehydrated alcohol also can be used a kind of the substituting in methyl alcohol, n-propyl alcohol, Virahol, propyl carbinol or the isopropylcarbinol, but preferred dehydrated alcohol.This is because dehydrated alcohol has environmental protection and the advantage such as renewable, has guaranteed that products therefrom is used for the security of healthcare products and medicine.
Described natural phosphatidyl choline is from the extract of soybean, yolk or pluck, and wherein the content of phosphatidylcholine is 20%～98%.
Catalyzer among the present invention is not only applicable to the preparation of L-α-glyceryl phosphatide phatidylcholine, also applicable to the extensive transesterification reaction such as the preparation of biofuel.The natural phospholipid deacylated tRNA base thing that simultaneously the present invention makes both can directly apply to medicine, healthcare products and functional food field, also can be used as the precursor of semi-synthetic phosphatide, for the preparation of the required synthetic phospholipid of pharmaceutical preparation.
Embodiment 1
Be that 40% soybean lecithin is dissolved in the 38mL methyl tertiary butyl ether with 5g phosphatidylcholine content, the elimination insolubles, add round-bottomed flask and place thermostat water bath to be heated to 40 ° of C, under this temperature condition, adding 1.2mL dehydrated alcohol and 0.8mL concentration is the ethanolic soln of the bursine of 0.3mol/L again, stirring reaction 2 hours.
Reaction is outwelled supernatant liquor after finishing; the oily throw out is dissolved with the 5mL anhydrous methanol; and adding 20mL methyl tertiary butyl ether precipitates; the fully rear abandoning supernatant of precipitation; repeat again 3 times with dissolve with methanol and with the operation of methyl tertiary butyl ether precipitation; at last the oily product that obtains is carried out vacuum-drying under the condition that Vanadium Pentoxide in FLAKES exists; obtaining the 1.021g outward appearance is that flaxen natural phospholipid deacylated tRNA base thing take GPC as the master (is GPC; the mixture of GPE and GPS); after testing; wherein the content of GPC accounts for 50.3% of product total mass, and yield is 76.0%.
Embodiment 2
The difference of present embodiment and embodiment 1 is, be that 60% soybean lecithin is dissolved in the 30mL methyl tertiary butyl ether with 5g phosphatidylcholine content, the elimination insolubles, add round-bottomed flask and place thermostat water bath to be heated to 50 ° of C, under this temperature condition, adding 8mL dehydrated alcohol and 2mL concentration is the ethanolic soln of the bursine of 0.3mol/L again, stirring reaction 1 hour.It is that flaxen after testing, wherein the content of GPC accounts for 73.2% of product total mass take GPC as main natural phospholipid deacylated tRNA base thing (being the mixture of GPC, GPE and GPS) that present embodiment obtains the 1.086g outward appearance, and yield is 78.4%.
Embodiment 3
The difference of present embodiment and embodiment 2 only is that phosphatidylcholine content is 95% in the soybean lecithin, and temperature of reaction is 40 ° of C, and the reaction times is 3h.After the reaction bottom oily throw out is dissolved with the 5mL anhydrous methanol, adding the 20mL methyl tertiary butyl ether precipitates again, the fully rear abandoning supernatant of precipitation, repeatedly carry out 3 times with dissolve with methanol and with the operation of methyl tertiary butyl ether precipitation, then carry out vacuum drying treatment under the condition that the product Vanadium Pentoxide in FLAKES is existed, and under the condition that diatomite exists, utilize volume ratio under 4 ° of C, to carry out crystallization for the dehydrated alcohol of 6:4 and the mixed solution of ether, obtain GPC crystal 1.026g.133 ° of C of fusing point,
(10% the aqueous solution), results of elemental analyses is: C, 37.1%; H, 7.80%; N, 5.43%.Take deuterated methanol as solvent,
1The position of main peaks: 4.36 (m, 2H) in the H NMR spectrogram, 3.91 (m, 2H), 3.82 (m, 1H), 3.61 (m, 2H), 3.58 (m, 2H), 3.27 (s, 9H).
Embodiment 4
The difference of present embodiment and embodiment 3 is, is that 90% soybean lecithin is dissolved in the 30mL methyl tertiary butyl ether with 2g phosphatidylcholine content, adds 10mL dehydrated alcohol and 0.145 bursine, 30 ° of C of temperature of reaction, stirring reaction 0.3 hour.Present embodiment obtains the intimate colourless GPC of being of 0.409g outward appearance, and purity is higher, and yield is 67.2%.
Embodiment 5
The difference of present embodiment and embodiment 2 is, be that 90% soybean lecithin is dissolved in the 25mL methyl tertiary butyl ether with 1g phosphatidylcholine content, add round-bottomed flask and place thermostat water bath to be heated to 25 ° of C, under this temperature condition, adding 11.5mL dehydrated alcohol and 3.5mL concentration is the ethanolic soln of the bursine of 0.3mol/L again, stirring reaction 4 hours.Present embodiment obtains the intimate colourless GPC of being of 0.132g outward appearance, and yield is 43.4%.
Embodiment 6
The difference of present embodiment and embodiment 5 is, be that 95% soybean lecithin is dissolved in the 25mL methyl tertiary butyl ether with 0.4g phosphatidylcholine content, regulate its temperature to 5 ° C, under this temperature condition, adding 13mL dehydrated alcohol and 2mL concentration is the ethanolic soln of the bursine of 0.3mol/L again, stirring reaction 4 hours.Present embodiment obtains the intimate colourless GPC of being of 0.0696g outward appearance, and purity is higher, and yield is 54.2%.
Embodiment 7
The difference of present embodiment and embodiment 3 is, adopts propyl carbinol to replace ethanol to react in the reaction.Present embodiment obtains the intimate colourless GPC of being of 0.832g outward appearance, and yield is 54.6%.
Claims (3)
1. the preparation method of natural L-α-glyceryl phosphatide phatidylcholine is characterized in that, concrete preparation process is as follows:
The natural phosphatidyl choline of known phosphatidylcholine content is dissolved in methyl tertiary butyl ether, adjusts the temperature to 5～55 ° of C behind the elimination insolubles; Under this temperature condition, be 10:1～600:1 according to anhydrous low-carbon alcohol and phosphatidylcholine mol ratio, add the pure and mild catalyzer bursine of anhydrous low-carbon, the consumption that makes bursine in the reaction system is every liter of 1～30mmol, stirring reaction 0.25～4 hour; Reaction is outwelled supernatant liquor after finishing; with oily throw out anhydrous alcohol solution; and precipitate with methyl tertiary butyl ether; the fully rear abandoning supernatant of precipitation; repeatedly precipitate 2～3 times with anhydrous alcohol solution and with methyl tertiary butyl ether again; the oily product that obtains is carried out vacuum-drying in the presence of Vanadium Pentoxide in FLAKES, namely obtain take the mixture of glyceryl phosphatide phatidylcholine as main natural phospholipid deacylated tRNA base thing.
2. the preparation method of natural L-α as claimed in claim 1-glyceryl phosphatide phatidylcholine is characterized in that, described anhydrous low-carbon alcohol adopts a kind of in methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol or the isopropylcarbinol.
3. the preparation method of natural L-α as claimed in claim 1-glyceryl phosphatide phatidylcholine is characterized in that, described natural phosphatidyl choline is from the extract of soybean, yolk or pluck, and wherein the content of phosphatidylcholine is 20%～98%.
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| CN115785146A (en) * | 2022-12-09 | 2023-03-14 | 黑龙江八一农垦大学 | Method for preparing glycerol phosphatidylcholine by alkaline process |
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