CN106928286B - N-(N '-oleoyl glutamine acyl)-Glucosamine and preparation method thereof - Google Patents
N-(N '-oleoyl glutamine acyl)-Glucosamine and preparation method thereof Download PDFInfo
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- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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Abstract
N-(N '-oleoyl glutamine acyl)-Glucosamine and preparation method thereof, it is related to technical field of chemical medicine, the DMF solution of oleic acid is reacted and filtered after a certain period of time with n-hydroxysuccinimide (NHS) and dicyclohexylcarbodiimide (DCC) mixing, filtrate is obtained；Glutamine and potassium carbonate are dissolved in the water, filtrate is added dropwise under the conditions of ice-water bath, N- acyl group glutamine solution is obtained after room temperature reaction；By N- oleoyl glutamine solution tune it is neutral after with aminoglucose hydrochloride, sodium bicarbonate, 1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride hybrid reaction, generate N-(N '-oleoyl glutamine acyl)-Glucosamine, it is the good biocompatibility of product, efficient, nontoxic, it can be used for the environmentally protective alcohol-soluble surfactant polymerizeing.
Description
Technical field
The present invention relates to technical field of chemical medicine, and in particular to the preparation method of surfactant.
Background technique
Since surfactant has excellent application performance, have in industrial production and daily life extensive
Application.All the time, people never stopped the R and D to novel surfactant.Especially raw material sources are wide
General, good biocompatibility, the exploitation of the unique surfactant of function one of has been a hot spot of research.
Since surfactant can be aligned in incompatible two-phase interface, this makes surfactant be related to two-phase
There is advantageous advantage in terms of certain properties at interface.When such as emulsion polymerization, surfactant will be often used,
So that reaction solution to be polymerized is dispersed into the state of lotion, the partial size of polymer is obtained in this way up to micron order, and uniform and stable.For
It prepares submicron order (or nanoscale) polymer microballoon, often requires to use a large amount of surfactant in preparation lotion,
And need using cosurfactant (such as small molecule alcohol), to reduce the surface tension of lotion microballoon, to realize microemulsified
Purpose.But due to using the concentration of surfactant high, remaining surfactant tends not to thoroughly elute in polymer,
Large effect often is generated to the property of polymer microballoon.Therefore find that a kind of emulsifying capacity is strong, to the stabilization of lotion droplet
Property it is helpful, and the less big surfactant of dosage becomes a direction to have a great attraction.
Glucosamine also known as gucosamine, are widely present in nature, 2-amino-2-deoxy-D-Glucose usually with
N- acetyl derivative (such as chitin) is present in micro- life in the form of N- sulfuric ester and N- acetyl -3-O- lactic acid ether (muramic acid)
In object, the polysaccharide of animal origin and combination polysaccharide.Its final catabolite as chitin has certain pharmacological function, and
With preferable filming performance, in field of pharmaceutical biology using relatively broad.Contain polyhydroxy in glucosamine molecules structure
And amino, it is good water-soluble outer except itself having, can also carry out N- is acylated, be alkylated, amino acid derivativges and O- are Carboxylation,
Phosphatide, alkene derivatives etc. modify chemical modification.Such as Glucosamine and cholic acid modification are prepared into novel derivative, it can
As the drug or introducing polymerizable groups for the treatment of osteoarthritis as cartilage repair material.But made using Glucosamine
It is actually rare for the report of surfactant.
Amino acid is the basis for constituting protein, is the primitive substance for constituting life.The basic knot of common amino acid
Structure is similar, and different amino acid side chains brings the different functional character of amino acid.Usual amino acid surfactant is mainly
Long chain fatty acyl is introduced on the amino of amino acid, and corresponding surfactant can be obtained after being then neutralized into salt.Commonly
Amino acid has sarcosine, glutamic acid, serine, alanine, picks propylhomoserin, leucine etc., wherein the most normal with sarcosine, glutamic acid
With.Used fatty acid is divided into two kinds of saturation and unsaturation, as oleic acid, oleic acid, cocinic acid, palmitoleic acid, hard oil are sour, pungent
Acid, capric acid etc..Especially unsaturated fatty acid, due to, with double bond, can be used for participating in polymerization reaction in molecular structure,
The surfactant that this can polymerize exploitation is very crucial.
Glucosamine mainly exists with the structure of pyranose, has preferable filming performance.It is generally acknowledged that preferably at
Film properties are advantageous the stabilization at interface.So if this property can be introduced among surfactant, in lotion
Play the role of stable emulsion droplet when polymerization, at the same time it is wished that playing using amino acid hydrophilic side-chains reduces lotion droplet surface
The effect (such as the effect of the small molecular alcohol when preparing microemulsion) of tension, therefore hydrophilic amino acid and Glucosamine are coupled
Afterwards, it is re-introduced into long chain oleophillic base, it is likely that realize the emulsion polymerization of submicrometer structure.In addition, if surfactant itself
Polymerization is participated in, is equivalent to and secures one layer of hydrophilic film on polymerizing microballoons surface, it is (this to melt to the fusion between emulsion droplet
Conjunction is the one of the major reasons for causing emulsion polymerization microballoon to grow up) play certain restriction effect.
Summary of the invention
The present invention is based on the above imaginations to propose a kind of N-(N '-oleoyl glutamine acyl)-Glucosamine, molecular structure
Formula is as follows:
Product of the present invention be it is a kind of with good biocompatibility, it is efficient, nontoxic, can be used for polymerize environmentally protective alcohol it is molten
Property surfactant, although solubility is less big in water, but still can have surface-active.Such surfactant has
Preferable filming performance, property is mild, because it can be participated in polymerization reaction, other than for emulsion polymerization, in biological function
It is had a good application prospect in material.
It is another object of the present invention to propose the above N-(N '-oleoyl glutamine acyl) preparation method of-Glucosamine.
The present invention the following steps are included:
1) DMF solution of oleic acid is mixed and is stirred with n-hydroxysuccinimide (NHS) and dicyclohexylcarbodiimide (DCC)
It mixes reaction to filter after a certain period of time, obtains filtrate；
2) glutamine and potassium carbonate are dissolved in the water, above-mentioned filtrate is added dropwise under the conditions of ice-water bath, drips and is placed on
It reacts at room temperature, N- acyl group glutamine solution is made；
3) pH value of N- oleoyl glutamine solution is adjusted to after neutrality and aminoglucose hydrochloride, sodium bicarbonate, 1-
The mixing of (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride is reacted, and N-(N '-oleoyl glutamine acyl is generated) -
Glucosamine crude product.
Reaction equation of the invention is as follows:
The invention has the advantages that synthetic reaction is simple, high income, reaction can be quantified.Contain since first step reaction has used
(active ester is formed) after long chain fatty acids are activated, NHS is released after being coupled with glutamine, when being coupled with Glucosamine
Aqueous condensation reagent EDC(1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride can be directly added into) it can be in water
Reaction is completed, therefore second step reaction (with amino acid couplings) can carry out third step reaction (with Glucosamine idol without separating
Connection).One pot reaction can be achieved in this way, greatly save reaction time and cost.
Alkali used in oleic acid active ester and glutamine coupling reaction selects potassium carbonate.This is because potassium carbonate and paddy amine acyl
The carboxylic acid of amine acts on forming saleratus, and in addition reaction need not add alkali again, to simplify technique.
Prepare N-(N '-oleoyl glutamine acyl)-Glucosamine crude product when, due to containing in aminoglucose hydrochloride
Hydrochloric acid, therefore neutralized with sodium bicarbonate.Due to the system that reaction system is water phase, using water-soluble 1- (3- dimethylamino third
Base) -3- ethyl-carbodiimide hydrochloride be condensing agent, can make reaction completed in one pot, eliminate intermediary separation trouble.
Surfactant crude product is obtained by process above, fine work can also be obtained using following methods: by N-(N '-oil
Acyl glutamine acyl) after-Glucosamine crude product is dissolved in ethyl alcohol, then it is added drop-wise to distilled water precipitation, the vacuum drying of centrifuging and taking solid phase,
Up to N-(N '-oleoyl glutamine acyl)-Glucosamine fine work.
Detailed description of the invention
Fig. 1 is N-(N '-oleoyl glutamine acyl)-Glucosamine infrared spectrum.
Such as the electron microscope that Fig. 2 is submicrometer structure polymerizing microballoons.
Specific embodiment
(1) first 0.282g(1.0mmol) oleic acid is dissolved in anhydrous DMF, 0.12g(1.05mmol is added) NHS(N- hydroxyl
Succinimide) and 0.226g(1.1mmol) dicyclohexylcarbodiimide (DCC), it filters, obtains after being stirred to react 10~12 hours
Filtrate (I).Glutamine 0.146g(1mmol is taken again) and potassium carbonate 0.138g(1mmol) be dissolved in suitable quantity of water, it is placed in ice water
In bath, filtrate (I) slowly is added dropwise, drips postposition and reacts at room temperature 24 hours, N- acyl amino acid solution is made.
(2) pH of N- oleoyl glutamine solution is adjusted with 3N hydrochloric acid to neutrality, and 0.216g Glucosamine is then added
Hydrochloride, 0.84g sodium bicarbonate, 0.203gEDAC(1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride), in 0
DEG C to reacting at room temperature for 24 hours, it is centrifuged, obtains N-(N '-oleoyl glutamine acyl)-Glucosamine crude product.
(3) by N-(N '-oleoyl glutamine acyl)-Glucosamine crude product is dissolved in ethanol in proper amount, it is added drop-wise to distilled water
It is precipitated, is centrifuged, is dried in vacuo up to the higher product of purity.
(4) N-(N '-oleoyl glutamine acyl prepared by this method)-Glucosamine infrared spectrum it is as shown in Figure 1.
In 3327cm in Fig. 1-1Neighbouring broad peak is mainly O-H, amino (and amide groups) on hydroxyl on Glucosamine
Upper N-H stretching vibration peak, 2926 cm-1~2851 cm-1The stretching vibration peak of c h bond on methyl and methylene is nearby showed,
Therefore it confirmed the presence of long chain alkane structure；1625.68 cm-1Place's absorption is the stretching vibration peak of mainly carbonyl.
(5) result of elemental analysis
Through elemental analysis, each element content are as follows: C61.1%, H9.39%, N7.40%, O22.34%, with notional result basic one
It causes.
It can be seen that achieving N-(N '-oleoyl glutamine acyl using this method)-Glucosamine.
(6) surface tension test in target compound saturated solution:
By N-(N '-oleoyl glutamine acyl)-Glucosamine is dissolved in a certain amount of distilled water, ultrasound 0.5 hour, high speed
It is centrifuged (revolving speed: 12000r/min), supernatant measurement surface tension (sessile drop method) is taken to see the table below:
The surface tension of 1 target compound near saturated solution of table
| Solution concentration (nearly saturation) | Surface tension 10-3N·m-1 |
| 0.097% | 41.7 |
(7) applicating example:
The present invention can be used for the preparation of polymer sub-micron microballoon, and method is as follows.
EGDMA, the 8.2mgAIBN for weighing 0.2973mg, are dissolved in 5mL ethyl acetate, then take 60mL N-(N '-oleoyl
Glutamine acyl) the nearly saturated aqueous solution of-Glucosamine, ethyl acetate solution is slowly added drop-wise in this aqueous solution, N is led to2Gas
15 minutes, ultrasound 15 minutes was placed in 2000r/min in heat collecting type constant-temperature heating magnetic stirring apparatus, 60 DEG C of reaction certain times.
Polymeric solution adds acetone precipitation, and centrifugation is collected precipitating, is added in Soxhlet extractor after being suspended with ethanol in proper amount, extracts 48 hours,
Obtain submicrometer structure polymerizing microballoons.
The electron microscope of submicrometer structure polymerizing microballoons as shown in Figure 2, it is seen that: the partial size of microballoon prepared by this method 50nm~
2000nm, particle size difference is less big (but having certain clustering phenomena), illustrates N-(N '-oleoyl glutamine acyl)-amino Portugal
Grape sugar can be completely used for ethyl acetate/water emulsion polymerization.
Claims (3)
1.N-(N '-oleoyl glutamine acyl)-Glucosamine, molecular structural formula is as follows:
。
2. N-(N '-oleoyl glutamine acyl as described in claim 1) preparation method of-Glucosamine, it is characterised in that packet
Include following steps:
1) DMF solution of oleic acid is reacted into certain time with n-hydroxysuccinimide and dicyclohexylcarbodiimide mixing
After filter, obtain filtrate；
2) glutamine and potassium carbonate are dissolved in the water, above-mentioned filtrate is added dropwise under the conditions of ice-water bath, drips and is placed on room temperature
N- oleoyl glutamine solution is made in lower reaction；
3) pH value of N- oleoyl glutamine solution is adjusted to after neutrality and aminoglucose hydrochloride, sodium bicarbonate, 1- (3- bis-
Methylaminopropyl) -3- ethyl-carbodiimide hydrochloride mixing reacted, generate N-(N '-oleoyl glutamine acyl)-amino Portugal
Grape sugar crude product.
3. N-(N '-oleoyl glutamine acyl according to claim 2) preparation method of-Glucosamine, it is characterised in that:
By N-(N '-oleoyl glutamine acyl) after-Glucosamine crude product is dissolved in ethyl alcohol, then it is added drop-wise to distilled water precipitation, centrifuging and taking is solid
Mutually vacuum drying is to get N-(N '-oleoyl glutamine acyl)-Glucosamine fine work.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0385287A2 (en) * | 1989-02-28 | 1990-09-05 | Forschungszentrum Jülich Gmbh | Process for the preparation of D-mannosamine derivatives |
| CN101235057A (en) * | 2008-03-07 | 2008-08-06 | 广州拜恩化学科技有限公司 | Aminoglucose unsaturated fatty acid salt and application of the same in preparing medicament for curing nerve immunity incretion disease |
| CN101343313A (en) * | 2008-09-03 | 2009-01-14 | 南京农业大学 | Glucose dipeptide compounds, preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5663991A (en) * | 1979-10-29 | 1981-05-30 | Takeda Chem Ind Ltd | Glucosamine derivative and its preparation |
| US8212076B2 (en) * | 2006-08-04 | 2012-07-03 | Covalence, Inc. | Prevention of cellular senescence in mammals by natural peptide complexes |
-
2017
- 2017-04-06 CN CN201710219515.4A patent/CN106928286B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0385287A2 (en) * | 1989-02-28 | 1990-09-05 | Forschungszentrum Jülich Gmbh | Process for the preparation of D-mannosamine derivatives |
| CN101235057A (en) * | 2008-03-07 | 2008-08-06 | 广州拜恩化学科技有限公司 | Aminoglucose unsaturated fatty acid salt and application of the same in preparing medicament for curing nerve immunity incretion disease |
| CN101343313A (en) * | 2008-09-03 | 2009-01-14 | 南京农业大学 | Glucose dipeptide compounds, preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 刘玮炜 等.N-硝基苯甲酰基-1,3，4,6-四-O-乙酰基-2-脱氧-ß-D-氨基葡萄糖的合成与表征.《华侨大学学报（自然科学版）》.2013,第34卷(第1期),第56-58页. |
| 脂肪酰化、羟烷化氨基葡萄糖表面活性剂的制备及其性能研究;田亚琴;《中国优秀硕士论文全文数据库（电子期刊）》;20110615(第6期);B016-176页 |
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Effective date of registration: 20230327 Address after: No. 5 Huaye Road, Renhe Town, Baiyun District, Guangzhou City, Guangdong Province, 510000 Patentee after: GUANGZHOU BITING COSMETICS Co.,Ltd. Address before: 225000 Huayang Xi Road, Yangzhou, Jiangsu 199 Patentee before: YANGZHOU POLYTECHNIC INSTITUTE |