JPH04282394A - Production of phosphatidylcholine - Google Patents
Production of phosphatidylcholineInfo
- Publication number
- JPH04282394A JPH04282394A JP12561291A JP12561291A JPH04282394A JP H04282394 A JPH04282394 A JP H04282394A JP 12561291 A JP12561291 A JP 12561291A JP 12561291 A JP12561291 A JP 12561291A JP H04282394 A JPH04282394 A JP H04282394A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- phosphatidylcholine
- flash chromatography
- diacylglycero
- oxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 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 15
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 238000003818 flash chromatography Methods 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract 4
- 239000000126 substance Substances 0.000 claims description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 abstract description 11
- 150000003512 tertiary amines Chemical class 0.000 abstract description 4
- 239000007795 chemical reaction product Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 description 22
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- OLSFRDLMFAOSIA-UHFFFAOYSA-N 2-chloro-1,3,2-dioxaphospholane Chemical compound ClP1OCCO1 OLSFRDLMFAOSIA-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 150000001982 diacylglycerols Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- OQQOAWVKVDAJOI-UHFFFAOYSA-N (2-dodecanoyloxy-3-hydroxypropyl) dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCC OQQOAWVKVDAJOI-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- NYKRTKYIPKOPLK-UHFFFAOYSA-N 1-bromo-2-dichlorophosphoryloxyethane Chemical compound ClP(Cl)(=O)OCCBr NYKRTKYIPKOPLK-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- FGPNKELZRNZASJ-UHFFFAOYSA-M 2-bromoethyl(trimethyl)azanium;2,4,6-trinitrophenolate Chemical compound C[N+](C)(C)CCBr.[O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O FGPNKELZRNZASJ-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- -1 ODS Chemical compound 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000005703 Trimethylamine hydrochloride Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000006177 alkyl benzyl group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical compound COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- SZYJELPVAFJOGJ-UHFFFAOYSA-N trimethylamine hydrochloride Chemical compound Cl.CN(C)C SZYJELPVAFJOGJ-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【０００１】0001
【産業上の利用分野】本発明は、ホスファチジルコリン
の改良された製造法に関するものである。FIELD OF THE INVENTION This invention relates to an improved method for producing phosphatidylcholine.
【０００２】0002
【従来の技術】ホスファチジルコリンは、乳化剤，分散
剤あるいはリポソーム製剤として広く食品，化粧品，医
薬品等の分野で使用されている。ホスファチジルコリン
の製造は、天然由来の原料を用いる方法と非天然由来の
原料から製造する場合がある。しかし、天然由来の場合
は微量成分の除去が困難であるとともに、最終生成物に
好ましくない成分が残存したり、反応工程が複雑であっ
たり、収率，反応時間，副生成物の面で問題がある。こ
のように、天然由来の原料を用いてホスファチジルコリ
ンを製造する方法は、リポソーム，乳化剤および医薬品
原料など生体内に直接投与する場合には必ずしも適当で
はない。BACKGROUND OF THE INVENTION Phosphatidylcholine is widely used as an emulsifier, dispersant, or liposome preparation in the fields of foods, cosmetics, pharmaceuticals, etc. Phosphatidylcholine may be produced using naturally derived raw materials or non-naturally derived raw materials. However, in the case of natural sources, it is difficult to remove trace components, undesirable components may remain in the final product, the reaction process is complicated, and there are problems in terms of yield, reaction time, and by-products. There is. As described above, the method of producing phosphatidylcholine using naturally derived raw materials is not necessarily suitable for direct administration into living organisms such as liposomes, emulsifiers, and pharmaceutical raw materials.
【０００３】一方、非天然由来の原料を用いてホスファ
チジルコリンを製造する方法は、出発原料の由来が明確
であるため副生成物の予想も比較的容易である。製造法
としては、２−ブロモエチル＝ホスホロジクロリダート
を用いて合成するＨｉｒｔらの方法，リン酸ジエステル
第四級アンモニウム塩に１，２−ジブロモエタンで反応
させることにより得られるアルキル＝（２−ブロモエチ
ル）メチル＝ホスファートをトリメチルアミンで処理す
る方法，アルキルベンジルエステル銀塩を（２−ブロモ
エチル）トリメチルアンモニウム＝ピクラートでアルキ
ル化したのち、脱ベンジル化する方法，さらに２−クロ
ロ−２−オキソ−１，３，２−ジオキサホスホランの誘
導体に第三級アミンを反応させてホスファチジルコリン
を合成する方法（フランス特許第１５５１０６０号）等
が知られている。On the other hand, in the method of producing phosphatidylcholine using raw materials of non-natural origin, the origin of the starting raw materials is clear, so it is relatively easy to predict by-products. Examples of production methods include the method of Hirt et al., which synthesizes using 2-bromoethyl phosphorodichloridate, and the method of alkyl=(2- A method of treating bromoethyl)methyl phosphate with trimethylamine, a method of alkylating an alkylbenzyl ester silver salt with (2-bromoethyl)trimethylammonium picrate and then debenzylating it, and a method of debenzylating 2-chloro-2-oxo-1, A method is known in which phosphatidylcholine is synthesized by reacting a 3,2-dioxaphosphorane derivative with a tertiary amine (French Patent No. 1551060).
【０００４】0004
【発明が解決しようとする課題】しかしながら、これら
のいずれの方法も、生成物の分取乃至精製については触
れるところが少ない。分取精製手段としては、一般にオ
ープンカラム法，ＨＰＬＣ法などが考えられるが、処理
量，コスト面などで必ずしも満足できるものとはいえな
いのが現状である。[Problems to be Solved by the Invention] However, in all of these methods, there is little mention of separation or purification of the product. Generally, open column methods, HPLC methods, etc. can be considered as preparative purification methods, but at present these methods are not necessarily satisfactory in terms of throughput, cost, etc.
【０００５】本発明はこれらの問題点を解決するための
もので、適切な分取乃至精製法を用いて収率良くホスフ
ァチジルコリンを製造する方法を提供することを目的と
する。The present invention is intended to solve these problems, and aims to provide a method for producing phosphatidylcholine in good yield using appropriate fractionation and purification methods.
【０００６】[0006]
【課題を解決するための手段】本発明は、ホスファチジ
ルコリンの製造法に関するものであって、下記の一般式
（Ｉ）または（ＩＩ）で表されるジアシルグリセロ−１
，３，２−ジオキサホスホラン−２−オキシドと一般式
（ＩＩＩ）で表される第三級アミンとを反応させて、一
般式（ＩＶ）または（Ｖ）で表されるホスファチジルコ
リンを製造する際に、フラッシュクロマトグラフィーを
用いて目的物を分取することを特徴とするホスファチジ
ルコリンの製造法である。[Means for Solving the Problems] The present invention relates to a method for producing phosphatidylcholine, which comprises diacylglycero-1 represented by the following general formula (I) or (II).
, 3,2-dioxaphosphorane-2-oxide and a tertiary amine represented by general formula (III) are reacted to produce phosphatidylcholine represented by general formula (IV) or (V). This method of producing phosphatidylcholine is characterized by separating the target product using flash chromatography.
【化１】[Chemical formula 1]
【化２】[Case 2]
【化３】[C3]
【化４】[C4]
【化５】
（式中Ｒ１，Ｒ２はアルキル基を示し、分岐を有しても
よい。Ｒ３，Ｒ４およびＲ５はアルキル基を示す。）embedded image (In the formula, R1 and R2 represent an alkyl group and may have a branch. R3, R4 and R5 represent an alkyl group.)
【
０００７】フラッシュクロマトグラフィーは、１９７８
年Ｓｔｉｌｌらによって提唱された分取方法の１つであ
り（Ｊ．Ｏｒｇ．Ｃｈｅｍ．４３（１４）２９２３，１
９７８）、耐圧性のあるカラムを使用して圧力をかけて
移動相を流下させるクロマトグラフィー法である。この
方法は、オープンカラム法に比べ加圧で移動相を流下さ
せるため、処理時間が大幅に軽減できる。また、。ＨＰ
ＬＣ法と比べた場合、１回の処理量が格段に多く、設備
面においても低コストで処理することができる。[
Flash chromatography was introduced in 1978.
It is one of the preparative methods proposed by Still et al. (J. Org. Chem. 43 (14) 2923, 1
978) is a chromatography method in which a pressure-resistant column is used to force the mobile phase to flow down. This method allows the mobile phase to flow down under pressure compared to the open column method, so the processing time can be significantly reduced. Also,. HP
When compared with the LC method, the amount of processing at one time is significantly larger, and processing can be performed at low cost in terms of equipment.
【０００８】フラッシュクロマトグラフィーの基本的な
システムは、０．１〜１０００ｌの容量の耐圧性カラム
を使用し、コンプレッサーで加圧して移動相を流下させ
る。カラム流速は線速度（ＳＶ値）で１〜２０ｃｍ／ｍ
ｉｎが適当であり、コンプレッサーの圧力で調整を行う
。分取はＵＶ，ＲＩ等の検出器を用いて必要な画分を取
る。また、用いる充填剤はシリカゲル，ＯＤＳ，イオン
交換樹脂等、必要に応じて選択する。The basic system of flash chromatography uses a pressure-resistant column with a capacity of 0.1 to 1000 liters, and pressurizes it with a compressor to cause the mobile phase to flow down. Column flow rate is 1 to 20 cm/m in linear velocity (SV value)
In is appropriate, and the pressure is adjusted by the compressor pressure. For fractionation, necessary fractions are taken using a UV, RI, etc. detector. Further, the filler to be used may be selected from silica gel, ODS, ion exchange resin, etc. as necessary.
【０００９】前記のジアシルグリセロ−１，３，２−ジ
オキサホスホラン−２−オキシドの合成法としては、グ
リセロールと２−クロロ−２−オキソ−１，３，２−ジ
オキサホスホランを反応後、アシル基を導入する方法，
ジアシルグリセロールとエチレン＝ホスホロクロリダイ
トを反応後、酸化させる方法，三塩化リンを出発原料と
して２−クロロ−２−オキソ−１，３，２−ジオキサホ
スホランを合成後、ジアシルグリセロールと反応させる
方法などがある。しかし、以上は例示であり、本発明は
これらに限定されない。[0009] As a method for synthesizing the diacylglycero-1,3,2-dioxaphosphorane-2-oxide, glycerol and 2-chloro-2-oxo-1,3,2-dioxaphosphorane are reacted. After that, the method of introducing an acyl group,
A method in which diacylglycerol and ethylene phosphorochloridite are reacted and then oxidized. 2-chloro-2-oxo-1,3,2-dioxaphosphorane is synthesized using phosphorus trichloride as a starting material, and then reacted with diacylglycerol. There are ways to do this. However, the above are examples, and the present invention is not limited thereto.
【００１０】0010
【実施例】（１）２−クロロ−２−オキソ−１，３，２
−ジオキサホスホランの合成
三塩化リン２．４モルを乾燥塩化メチレン４００ｍｌに
溶解し、かきまぜながらエチレングリコール２．４モル
を滴下した。塩化水素の発生がおさまったのち、溶媒を
留去し残留物を減圧蒸留しエチレン＝ホスホロクロリダ
イトを得た。ｂｐ６７．５〜６８．５℃／４５ｍｍＨｇ
，収率８５％（文献値Ｈ．Ｊ．Ｌｕｃａｓ．ｅｔ ａ
ｌ，Ｊ．Ａｍ．Ｃｈｅｍ．Ｓｏｃ．，７２，５４９１（
１９５０）から６６〜６８℃／４７ｍｍＨｇ）。エチレ
ン＝ホスホロクロリダイト２．０モルを３００ｍｌに溶
解し、かきまぜながら乾燥酸素を吹き込んだ。発熱がお
さまったのち、さらに１時間酸素を通じた。減圧留去後
、残留物を減圧留去した。ｂｐ１２０．０℃／３ｍｍＨ
ｇ，収率７０％（文献値Ｊ．Ｒ．Ｃｏｘ Ｊｒ．，Ｆ
．Ｈ．Ｗｅｓｔｈｅｉｍｅｒ，Ｊ．Ａｍ．Ｃｈｅｍ．Ｓ
ｏｃ．，８０，５５４１（１９５８）から９０℃／０．
８ｍｍＨｇ）。[Example] (1) 2-chloro-2-oxo-1,3,2
-Synthesis of Dioxaphosphorane 2.4 mol of phosphorus trichloride was dissolved in 400 ml of dry methylene chloride, and 2.4 mol of ethylene glycol was added dropwise while stirring. After the generation of hydrogen chloride subsided, the solvent was distilled off and the residue was distilled under reduced pressure to obtain ethylene phosphorochloridite. bp67.5-68.5℃/45mmHg
, yield 85% (literature value H.J. Lucas et a
l, J. Am. Chem. Soc. ,72,5491(
1950) to 66-68°C/47mmHg). 2.0 mol of ethylene phosphorochloridite was dissolved in 300 ml, and dry oxygen was blown into the solution while stirring. After the fever subsided, oxygen was passed for an additional hour. After evaporation under reduced pressure, the residue was evaporated under reduced pressure. bp120.0℃/3mmH
g, yield 70% (literature value J.R. Cox Jr., F.
．． H. Westheimer, J. Am. Chem. S
oc. , 80, 5541 (1958) to 90°C/0.
8mmHg).
【００１１】（２）１，２−ジラウロイルグリセロール
−１，３，２−ジオキサホスホラン−２−オキシドの合
成
１，２−ジラウロイルグリセロール０．３６モルとトリ
メチルアミン０．４モルのアセトン１０００ｍｌ溶液に
５〜１０℃で２−クロロ−２−オキソ−１，３，２−ジ
オキサホスホラン０．３６モルを滴下した。滴下後、室
温で６時間かきまぜた後、ドライボックス中でトリメチ
ルアミン塩酸塩を濾別した。(2) Synthesis of 1,2-dilauroylglycerol-1,3,2-dioxaphosphorane-2-oxide 1,2-dilauroylglycerol 0.36 mol and trimethylamine 0.4 mol in acetone 1000ml 0.36 mol of 2-chloro-2-oxo-1,3,2-dioxaphosphorane was added dropwise to the solution at 5-10°C. After the dropwise addition, the mixture was stirred at room temperature for 6 hours, and trimethylamine hydrochloride was filtered off in a dry box.
【００１２】（３）１，２−ジラウロイルグリセロ−３
−ホスファチジルコリンの合成
ステンレススチール製の円筒型オートクレーブに、１，
２−ジラウロイルグリセロ−１，３，２−ジオキサホス
ホラン−２−オキシドとトリメチルアミン０．４モルを
吸収させたアセトン溶液を加えて６０℃で２０時間反応
させた。析出した結晶を吸引濾過後、アセトンで再結晶
させて１，２−ジラウロイルグリセロ−３−ホスファチ
ジルコリンの粗反応物を得た。上記の反応物０．２モル
をメタノールに溶解後、フラッシュクロマトグラフィー
に供した。充填剤は、平均粒子系６０μｍのシリカゲル
を１０ｋｇ使用し、メタノールを移動相とし、線速度５
ｃｍ／ｍｉｎで処理した。ＵＶを検出器として使用し、
１，２−ジラウロイルグリセロ−３−ホスファチジルコ
リンの画分を分取した。収率３０％（純度９５％）。１
Ｈ−ＮＭＲ（δ，ＣＤＣｌ３）：０．８９（ｑ，６Ｈ，
ＣＨ３−），１．２８（ｓ，３２Ｈ，−ＣＨ２−），１
．５８（ｍ，２Ｈ，−ＣＨ２−ＣＨ２−Ｃ＝Ｏ），２．
２９（ｍ，２Ｈ，−ＣＨ２−Ｃ＝Ｏ），３．３９（ｓ，
９Ｈ，Ｎ（ＣＨ３）３），３．８３（ｓ（ｂｒ），２Ｈ
，−ＣＨ２−ＣＨ２−Ｎ），３．９４（ｍ，２Ｈ，３−
ｐｏｓｉｔｏｎ ｏｆ ｇｌｙｃｅｒｏｌ），４．
１３（ｓ（ｂｒ），２Ｈ，−ＣＨ２−ＣＨ２−Ｎ），４
．４０（ｍ，１Ｈ，１−ｐｏｓｉｔｏｎ ｏｆ ｇ
ｌｙｃｅｒｏｌ），５．２０（ｍ，１Ｈ，２−ｐｏｓｉ
ｔｏｎｏｆ ｇｌｙｃｅｒｏｌ）(3) 1,2-dilauroylglycero-3
- Synthesis of phosphatidylcholine In a stainless steel cylindrical autoclave, 1.
An acetone solution containing 2-dilauroylglycero-1,3,2-dioxaphosphorane-2-oxide and 0.4 mole of trimethylamine was added thereto, and the mixture was reacted at 60°C for 20 hours. The precipitated crystals were suction filtered and then recrystallized with acetone to obtain a crude reaction product of 1,2-dilauroylglycero-3-phosphatidylcholine. After dissolving 0.2 mol of the above reactant in methanol, it was subjected to flash chromatography. The filler used was 10 kg of silica gel with an average particle size of 60 μm, methanol was used as the mobile phase, and the linear velocity was 5.
cm/min. Using UV as a detector,
A fraction of 1,2-dilauroylglycero-3-phosphatidylcholine was collected. Yield 30% (purity 95%). 1
H-NMR (δ, CDCl3): 0.89 (q, 6H,
CH3-), 1.28 (s, 32H, -CH2-), 1
．． 58 (m, 2H, -CH2-CH2-C=O), 2.
29 (m, 2H, -CH2-C=O), 3.39 (s,
9H, N(CH3)3), 3.83(s(br), 2H
, -CH2-CH2-N), 3.94(m,2H,3-
position of glycerol), 4.
13(s(br),2H,-CH2-CH2-N),4
．． 40(m, 1H, 1-position of g
lycerol), 5.20 (m, 1H, 2-posi
ton of glycerol)
【００１３】[0013]
【発明の効果】フラッシュクロマトグラフィーを使用す
ることにより、必要画分を大量にかつ迅速に分取して、
目的物を高純度で得ることができる。また、ホスファチ
ジルコリン製造時に用いたトリメチルアミン等の有臭成
分を効率良く除去できる効果もある。[Effects of the invention] By using flash chromatography, necessary fractions can be quickly separated in large quantities.
The target product can be obtained with high purity. It also has the effect of efficiently removing odor components such as trimethylamine used in the production of phosphatidylcholine.
Claims (1)
表されるジアシルグリセロ−１，３，２−ジオキサホス
ホラン−２−オキシドと一般式（ＩＩＩ）で表される第
三級アミンとを反応させて、一般式（ＩＶ）または（Ｖ
）で表されるホスファチジルコリンを製造する際に、フ
ラッシュクロマトグラフィーを用いて目的物を分取する
ことを特徴とするホスファチジルコリンの製造法。 【化１】 【化２】 【化３】 【化４】 【化５】 （式中Ｒ１，Ｒ２はアルキル基を示し、分岐を有しても
よい。Ｒ３，Ｒ４およびＲ５はアルキル基を示す。）Claim 1: Diacylglycero-1,3,2-dioxaphosphorane-2-oxide represented by the following general formula (I) or (II) and a tertiary compound represented by the general formula (III) General formula (IV) or (V
) A method for producing phosphatidylcholine, which comprises separating the target product using flash chromatography. [Chemical 1] [Chemical 2] [Chemical 3] [Chemical 4] [Chemical 5] (In the formula, R1 and R2 represent an alkyl group and may have a branch. R3, R4 and R5 represent an alkyl group. .)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12561291A JP2933412B2 (en) | 1991-03-08 | 1991-03-08 | Method for producing phosphatidylcholine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12561291A JP2933412B2 (en) | 1991-03-08 | 1991-03-08 | Method for producing phosphatidylcholine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04282394A true JPH04282394A (en) | 1992-10-07 |
| JP2933412B2 JP2933412B2 (en) | 1999-08-16 |
Family
ID=14914400
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12561291A Expired - Fee Related JP2933412B2 (en) | 1991-03-08 | 1991-03-08 | Method for producing phosphatidylcholine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2933412B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106946936A (en) * | 2016-08-16 | 2017-07-14 | 南京构友生物材料有限公司 | The method that a kind of continuous flow reactor safe and efficient oxygen of 2 chlorine of oxidative synthesis 2 in utilization microchannel closes 1,3,2 dioxaphospholane |
-
1991
- 1991-03-08 JP JP12561291A patent/JP2933412B2/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106946936A (en) * | 2016-08-16 | 2017-07-14 | 南京构友生物材料有限公司 | The method that a kind of continuous flow reactor safe and efficient oxygen of 2 chlorine of oxidative synthesis 2 in utilization microchannel closes 1,3,2 dioxaphospholane |
| CN106946936B (en) * | 2016-08-16 | 2019-01-25 | 南京构友生物材料有限公司 | A method of 2-chloro-2-oxo-1,3,2-dioxaphospholane is synthesized using microchannel continuous flow reactor |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2933412B2 (en) | 1999-08-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1471920B1 (en) | Process for preparing water-soluble phosphonooxymethyl derivatives of alcohol and phenol | |
| US5430169A (en) | Method for preparation of sphingoid bases | |
| KR101278874B1 (en) | Method for preparing of 1-palmitoyl-3-acetylglycerol and Method for preparing of 1-palmitoyl-2-linoleoyl-3-acetyl glycerol using the same | |
| CN101891760A (en) | Improving one's methods of preparation oxidized phospholipids | |
| JP5044965B2 (en) | Method for producing α-glycerophosphorylcholine crystals | |
| US4382035A (en) | Glycerol-3-phosphoric acid halogenoalkyl esters and processes for their preparation and further conversion | |
| US4709083A (en) | Method of making boron analogues | |
| EP0486100A1 (en) | Process for preparing alpha-glycerophosphorylcholine | |
| JPH07291982A (en) | Production of glycerophospholipid | |
| EP0181721B1 (en) | Esters of boron analogues of amino acids | |
| JPH04282394A (en) | Production of phosphatidylcholine | |
| JPS63135395A (en) | Phospholipid derivative and production thereof | |
| JPH0248585A (en) | Phospholipid derivative and production thereof | |
| JP3477631B2 (en) | Purification method of 1,3-bis (3-aminopropyl) -1,1,3,3-tetraorganodisiloxane | |
| JPH0959292A (en) | Production of 4-aminopyrimidine nucleoside | |
| JPH11180929A (en) | Ester derivative | |
| Cheng‐Xiang et al. | Synthesis of 1, 2‐and 1, 3‐cyclic phospholipid conjugates of N1‐(2‐furanidyl)‐N3‐(2‐hydroxyethyl)‐5‐fluorouracil | |
| JP3619277B2 (en) | Method for producing dihydropolyprenyl monophosphate and its intermediate compound | |
| JP2024127824A (en) | Method for producing polyalkylene oxide-modified phospholipids | |
| WO2021132297A1 (en) | Carbacyclic phosphatidic acid compound | |
| WO2024185762A1 (en) | Method for producing polyalkylene oxide-modified phospholipid | |
| JPH07330783A (en) | Production of phosphoric ester derivative | |
| CN111087420A (en) | Preparation method of 1, 2-dipalmitoyl-SN-glycerol-3-phosphoric acid | |
| US20210107857A1 (en) | Method for producing 1-palmitoyl-2-linoleoyl-3-acetyl glycerol | |
| JP2002275187A (en) | Method for producing phosphatidylcholine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |