CN102876741B - Method for preparing myristyl serinate under lipase catalysis - Google Patents
Method for preparing myristyl serinate under lipase catalysis Download PDFInfo
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- CN102876741B CN102876741B CN201210321681.2A CN201210321681A CN102876741B CN 102876741 B CN102876741 B CN 102876741B CN 201210321681 A CN201210321681 A CN 201210321681A CN 102876741 B CN102876741 B CN 102876741B
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Abstract
The invention discloses a method for preparing myristyl serinate under lipase catalysis, belonging to the technical field of biocatalysis. The method comprises the following steps: in a complex system of a phosphate buffer solution and n-hexane, carrying out esterification reaction by serine and tetradecyl alcohol (myristyl alcohol) under lipase catalysis, and synthesizing the myristyl serinate, wherein the reaction temperature is 20-60 DEG C. The method for preparing the serine myristate under lipase catalysis disclosed by the invention has the advantages of moderate and safe reaction conditions, single product, easiness in purification process and good selectivity and the like, and provides a new way for preparing the myristyl serinate by bioanalysis.
Description
Technical field
The invention belongs to the preparation field of tetradecyl alcohol serine ester, particularly relate to the method for the synthetic tetradecyl alcohol serine ester of a kind of enzyme-catalyzed change, belong to biocatalysis technology field.
Background technology
Tetradecyl alcohol serine ester, synthetic ceramide type compound Trihydroxypalmitamido dydrmyristyl ether as by name in Ceramide HO3TM(chemistry, France Sederma S. A. exploitation), PMS (chemistry Palmitoyl myristyl serinate by name, CAS:15602-32-9, Korea S Pacific Ocean company develops) and Ceramide PC-104(chemical name 1, 3-bis-(N-(2-hydroxyethyl)-palmitoylamino)-2-hydroxypropane, Korea S Pacific Ocean company exploitation) etc. key intermediate, by Serine and long chain alkane alcohol-1-ten methane alcohol (tetradecyl alcohols, 1-tetradecanol, myristyl alcohol) esterification and generating, following formula is the structural formula of tetradecyl alcohol serine ester.
Ceramide type compound is the latest generation wetting Agent for Printing Inks of in recent years developing; the hydrophilic lipid of tool; very approaching with the speciality structure that forms keratoderma; can penetrate into skin; with the water combination in stratum corneum; form a kind of reticulated structure, pin moisture, there is the function of protection, skin care and moisturizing.A lot of results of study show in addition, and ceramide type compound can prevent anaphylaxis dermatosis and the brown class of check melanin.The nineties in last century, Japanese cosmetics of super quality city brings into use ceramide type compound, and up to the present this compounds is fast-developing with the rate of increase of annual 15% left and right as a kind of beauty treatment raw material of novelty, and the market requirement constantly expands.Rate of increase at this compounds of Switzerland with annual 35% left and right develops rapidly, except adding in makeup ceramide type compound, application in functional foodstuff is also very extensive, become at present a large focus of functional ingredient, by taking ceramide type compound, after intestinal absorption, enter blood circulation, make skin cells obtain good recovery and regeneration, play the effect delaying senility.More external famous cosmetics companies have released one after another in 10 years in the past containing the Novel advanced makeup of ceramide type compound, as skin type and hair care category product, and red in moisturizing, lipstick, muffin, eye shadow and perfumed soap etc.
The current domestic tetradecyl alcohol serine ester of also not producing, the main Shi of the production Korea S of this compounds and more American-European developed countries, production method is to utilize concentrated hydrochloric acid as catalyzer, high temperature reflux (75 ~ 95 ℃) 7-20 hour, the main drawback of this method is selectivity poor (Serine easily lactonizes), productive rate is low, later stage purification process is loaded down with trivial details, contaminate environment, consume energy high, synthetic product colour is darker, product purity is low etc., and and lipase has stereospecificity and high-efficiency catalytic activity, make radical reaction occur in needed position, and subsequent disposal, product purification is simpler, be applicable to suitability for industrialized production.
Summary of the invention
The method that the object of this invention is to provide synthetic Serine 14 esters of a kind of water and organic phase compound system enzyme-catalyzed change, synthetic method of the present invention improves the selectivity of esterification, the productive rate of Serine 14 esters reaches more than 80%, and reaction conditions is gentle, the method reaction conditions is safe, gentle, purifying is easy, and step is few, is convenient to suitability for industrialized production.Reaction equation:
Technical scheme of the present invention: the method for tetradecyl alcohol serine ester is prepared in the catalysis in organic phase and water compound system of a kind of lipase, according to following step, carry out: (1) take phosphate buffered saline buffer and normal hexane is reaction medium, with lipase-catalyzed Serine and tetradecyl alcohol, carry out esterification, synthetic tetradecyl alcohol serine ester
(2) after esterification finishes, filtered and recycled lipase, reaction liquid extracts 2 times by the ethyl acetate of same volume, 40 ~ 60 ℃ of vacuum of extraction liquid are revolved and steamed evaporative removal ethyl acetate, through silica gel column chromatography separating purification, obtain tetradecyl alcohol serine ester sterling, purity reaches more than 95%;
Wherein the described lipase of step (1) is Novozym 435; Lipozyme RMIM; Wherein said phosphate buffered saline buffer is the 0.1M phosphate buffered saline buffer of pH=6.98, the volume ratio of phosphate buffered saline buffer and normal hexane is 1:1 ~ 4:3, the condition of esterification is that substrate serine concentration is 50 ~ 150g/L, the mol ratio of Serine and tetradecyl alcohol is 1:1-1:5, the mass ratio of Serine and lipase is 10:1 ~ 10:4, esterification reaction temperature is 20 ~ 60 ℃, 18 ~ 60 hours stirring reaction time.
Wherein the solvent of the silica gel column chromatography separating purification described in step (2) is ethyl acetate, and elutriant is normal hexane: ether: acetic acid=88:10:2.
The present invention has reaction conditions gentleness, good reaction selectivity, and reaction product is single, and transformation efficiency is high, and product safety, subsequent purification are processed the plurality of advantages such as simple easy.Therefore, the present invention provides new approach for Biological preparation tetradecyl alcohol serine ester.
Accompanying drawing explanation
Wherein the HPLC of Fig. 1 tetradecyl alcohol serine ester schemes,
The mass spectrum of Fig. 2 tetradecyl alcohol serine ester.
Embodiment
Lipase of the present invention comprises that Novozym 435(derives from
candida antarctica); Lipozyme RMIM (derives from
rhizomucor miehei) all purchased from Novozymes Company.With specific embodiment, technical scheme of the present invention is described further below.
In the present invention, adopt HPLC to analyze the content of product tetradecyl alcohol serine ester in assaying reaction, chromatographic condition is OD-H chiral column, 30 ℃ of column temperatures, and moving phase is V (normal hexane): V (Virahol)=90:10, flow velocity is 1mL/min.Detector is light scattering detector (ELSD).
embodiment 1
Synthesizing of tetradecyl alcohol serine ester: take 2g Serine and add dissolving in 10mL 0.1M phosphate buffered saline buffer (pH=6.98), be placed in 50mL tool plug ground Erlenmeyer flask, and then add 10mL normal hexane (phosphate buffered saline buffer and normal hexane volume ratio 1:1) and 1g tetradecyl alcohol, lipase 0.1g, be placed in 30 ℃ of constant-temperature tables, 120rpm, reaction result follows the tracks of detection by thin-layer chromatography TLC and sampling HPLC analyzes.React after 24 hours, productive rate reaches more than 68%.Remove by filter lipase, with the extraction of 10 ~ 15mL ethyl acetate, ethyl acetate and normal hexane are removed in 40-50 ℃ of underpressure distillation, obtain white meat cardanol serine ester crude product.
With 200-300 order silica gel wet method dress post, elutriant is normal hexane: ether: acetic acid=88:10:2, with a small amount of elutriant, dissolve tetradecyl alcohol serine ester crude product, wet method loading, TLC follows the tracks of wash-out process, and the elutriant that contains single product obtaining is merged to evaporate to dryness, obtains white monoesters crystal, obtain tetradecyl alcohol serine ester sterling (purity is more than 95%), mass spectroscopy molecular weight is that its theoretical molecular of 300.9(is 301).
The HPLC figure of Fig. 1 tetradecyl alcohol serine ester sterling (HPLC testing conditions: OD-H chiral column, 30 ℃ of column temperatures,
v (normal hexane) : V ( virahol) =90:10, flow velocity is 1mL/min, ELSD detector), retention time is that 2.576min. Fig. 2 is tetradecyl alcohol serine ester sterling LC-MS figure, as can be seen from Figure 2, the molecular weight of tetradecyl alcohol serine ester is 300.9, conforms to theoretical molecular 301.
embodiment 2
Synthesizing of tetradecyl alcohol serine ester: take 2g Serine and add dissolving in 8mL 0.1M phosphate buffered saline buffer (pH=6.98), be placed in 50mL tool plug ground Erlenmeyer flask, and then add 6mL normal hexane and 1g tetradecyl alcohol (phosphate buffered saline buffer and normal hexane volume ratio 4:3), lipase 0.1g, be placed in 30 ℃ of constant-temperature tables, 120rpm, reaction result follows the tracks of detection by thin-layer chromatography TLC and sampling HPLC analyzes.React after 24 hours, productive rate reaches more than 65%.Remove by filter lipase, with the extraction of 10 ~ 15mL ethyl acetate, ethyl acetate and normal hexane are removed in 40-50 ℃ of underpressure distillation, obtain white meat cardanol serine ester crude product.By embodiment 1 method, cross silicagel column, obtain tetradecyl alcohol serine ester sterling (purity is more than 95%)
embodiment 3
Synthesizing of tetradecyl alcohol serine ester: take respectively 0.5g left and right Serine and 1g left and right tetradecyl alcohol, add the solvent that 15mL is different (acetone, normal hexane, cyclohexane and tetrahydrofuran (THF)), be placed in 4 50mL tool plug ground Erlenmeyer flasks, then add respectively lipase 0.1g, be placed in 30 ℃ of constant-temperature tables, 120rpm, reaction result follows the tracks of detection by thin-layer chromatography TLC and sampling HPLC analyzes.React after 24 hours, productive rate reaches respectively 18%, 32%, 27% and 21%.Remove by filter lipase and Serine, 40-50 ℃ of underpressure distillation, except desolventizing, obtains white meat cardanol serine ester and tetradecyl alcohol mixture.By embodiment 1 method, cross silicagel column, obtain tetradecyl alcohol serine ester sterling (purity is more than 95%).
Claims (2)
1. the method for tetradecyl alcohol serine ester is prepared in lipase catalysis in organic phase and water compound system, it is characterized in that carrying out according to following step: (1) take phosphate buffered saline buffer and normal hexane is reaction medium, with lipase-catalyzed Serine and tetradecyl alcohol, carry out esterification, synthetic tetradecyl alcohol serine ester
(2) after esterification finishes, filtered and recycled lipase, reaction liquid extracts 2 times by the ethyl acetate of same volume, and 40 ~ 60 ℃ of vacuum of extraction liquid are revolved and steamed evaporative removal ethyl acetate, through silica gel column chromatography separating purification, obtain tetradecyl alcohol serine ester sterling;
Wherein the described lipase of step (1) is Novozym 435 or Lipozyme RMIM; Wherein said phosphate buffered saline buffer is the 0.1M phosphate buffered saline buffer of pH=6.98, the volume ratio of phosphate buffered saline buffer and normal hexane is 1:1 ~ 4:3, the condition of esterification is that substrate serine concentration is 50 ~ 150g/L, the mol ratio of Serine and tetradecyl alcohol is 1:1-1:5, the mass ratio of Serine and lipase is 10:1 ~ 10:4, esterification reaction temperature is 20 ~ 60 ℃, 18 ~ 60 hours stirring reaction time.
2. the method for tetradecyl alcohol serine ester is prepared in a kind of lipase according to claim 1 catalysis in organic phase and water compound system, the solvent that it is characterized in that the silica gel column chromatography separating purification that step (2) is wherein described is ethyl acetate, and elutriant is normal hexane: ether: acetic acid=88:10:2.
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| CN101068537A (en) * | 2004-07-16 | 2007-11-07 | 马萨诸塞大学 | Lipid-amino acid conjugates and methods of use |
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Non-Patent Citations (6)
| Title |
|---|
| Geoffrey Hills,et al.Industrial use of lipases to produce fatty acid esters.《European Journal of Lipid Science and Technology》.2003,第105卷601-607. |
| Industrial use of lipases to produce fatty acid esters;Geoffrey Hills,et al;《European Journal of Lipid Science and Technology》;20031231;第105卷;601-607 * |
| 固定化脂肪酶合成肉豆蔻酸异丙酯的研究;尹春华等;《日用化学工业》;20091231;第39卷(第6期);405-408 * |
| 尹春华等.固定化脂肪酶合成肉豆蔻酸异丙酯的研究.《日用化学工业》.2009,第39卷(第6期),405-408. |
| 杨广花等.脂肪酶法催化胆固醇合成胆固醇棕榈酸酯的研究.《安徽农业科学》.2010,第38卷(第25期),13565-13566. |
| 脂肪酶法催化胆固醇合成胆固醇棕榈酸酯的研究;杨广花等;《安徽农业科学》;20101231;第38卷(第25期);13565-13566 * |
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Effective date of registration: 20181011 Address after: 226600 Jiangsu Haian County Qu Tang town industrial concentration area Patentee after: Jiangsu Yok Heng Biotechnology Co., Ltd. Address before: No. 1, Wujin District, Wujin District, Changzhou, Jiangsu Patentee before: Changzhou University |
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