CN102827036A - Menthyl ester derivative gel factor and preparation method thereof - Google Patents
Menthyl ester derivative gel factor and preparation method thereof Download PDFInfo
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- CN102827036A CN102827036A CN2012103519798A CN201210351979A CN102827036A CN 102827036 A CN102827036 A CN 102827036A CN 2012103519798 A CN2012103519798 A CN 2012103519798A CN 201210351979 A CN201210351979 A CN 201210351979A CN 102827036 A CN102827036 A CN 102827036A
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Abstract
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a menthyl ester derivative gel factor and a preparation method thereof, and a gel formed by the compound. The gel compound is prepared by respectively reacting (L-)menthyl chloroformate with L-lysine methyl ester or Boc-protected ethylenediamine. The gel compound forms an aquagel or organic gel under certain conditions, and has different gel properties; after esterifying menthol, the structure is more stable and easy to modify; the menthyl ester derivative introduced into the gel system as a novel gel factor can obtain a novel food or cosmetic additive having slow release function and continuous cooling effect; and the menthyl ester derivative is hopeful to be used in the fields of food or cosmetic additives, cell tissue engineering, drug release carriers and the like.
Description
Technical field
The invention belongs to the fine chemical technology field, be specifically related to menthyl ester derivatives class gel factor and preparation method thereof, and by the formed gel of this compounds.
Background technology
Low Molecular-Weight Gel (Organogel) or hydrogel (Hydrogel) are one type of special materials; Have liquid and solid character concurrently; It is the intermolecular ydrogen bonding through the gel factor; Pi-pi accumulation, Van der Waals force and other non-covalent interaction also wrap up all kinds of SOLVENTS or water and the colloid that forms.Low Molecular-Weight Gel has to external world IR makes it show huge application potential at bioengineered tissue, medicament transport, inorganic materials template, makeup, food, marine oil overflow, bio-sensing and aspects such as susceptible device susceptor preparation, propellant performance optimization with advantages such as heat are reversible rapidly, receives the increasingly extensive concern of people.In addition, amino acid derivative class hydrogel has advantages such as low toxicity, biodegradable, good biocompatibility, can be used as the timbering material of cell cultures and organizational project.Therapeutic Mineral Ice is spices and the freshener that people are familiar with the most, has peppermint fragrance and refrigerant effect, has antibacterial and anti-inflammation functions simultaneously, and has advantages such as cheap and easy to get, is widely used in the middle of daily use chemicals, food, medicine and the personal hygiene prod.Its structure after the Therapeutic Mineral Ice esterification is more stable; And be prone to modify; The menthyl ester verivate is introduced gelling system as the new type gel factor, can obtain to have the novel food product or the cosmetics additive of slow-release function and lasting cooling effect, be expected to simultaneously aspect drug release carrier, obtain to use.Therefore, the menthyl ester derivatives class organogel of design synthesizing new or the development and progress that hydrogel can promote novel material have huge application potential.
Summary of the invention
The object of the present invention is to provide a kind of structure and preparation method of the menthyl ester derivative gel factor, and this gellike factor formed gel and preparation method thereof in organic solvent and water.
The constitutional features of the gel factor provided by the invention is to be parent with the menthyl ester, and its general structure is following:
General molecular formula is:
[(C 10 H 19 O)-CONH-(CH 2 ) n -R]N=2-4 wherein, R represents t-butyl carbamate, methyl aminoacetate or Padil.
Among the present invention; The preparation method of above-claimed cpd is following: with chloroformic acid (left-handed) menthyl ester and L-lysine methyl ester or by the quadrol of the single protection of Boc in methylene dichloride or chloroform under the room temperature reaction spend the night and obtain the acyl derivative of peppermint ester; Deprotection or hydrolysis obtain target compound again, and compound method is simple.Amide group in the molecule is easy to form hydrogen bond, can realize the pectisation to organic solvent and water.In addition, this compounds can form difform nanometer micrometer structure in organic solvent or water.
The method that menthyl ester verivate according to the invention forms gel is: the mixed solvent that 1) in gelatinous cpd, adds the second alcohol and water of certain volume ratio; Being heated to dissolved state is cooled to room temperature again and can forms gel; Perhaps adding ethanol earlier dissolves it fully; Add entry more in certain proportion, can form gel under the room temperature.2) in gelatinous cpd, add entry, be heated to dissolved state and be cooled to room temperature again and can form hydrogel.
Its structure after the Therapeutic Mineral Ice esterification is more stable; And be prone to modify; The menthyl ester verivate is introduced gelling system as the new type gel factor; Can obtain to have the novel food product or the cosmetics additive of slow-release function and lasting cooling effect, be expected to simultaneously obtain to use in fields such as food or cosmetics additive, cellular system engineering, drug release carriers.
Technique effect of the present invention:
Select below three kinds of compound as (R: t-butyl carbamate, n=2), b (R: methyl aminoacetate, n=4), (R: Padil n=4) for representative, specifically describes technique effect of the present invention from several aspects to c.
1. the gellifying property of gelatinous cpd (the gel factor).
Compound
aCan be dissolved in most of organic solvent, but in the certain mixed solvent of ethanol and water, can form the oyster white gel, this gel has thermal reversibility matter; Promptly become colloidal sol after the heating, form gel after the cooling once more, this process can be repeatedly repeatedly; Its transition temperature is 75 ℃, and minimum one-tenth gel strength is 11.8mg/mL, for example in the sealed vial that contains the 10mg sample; Add earlier 300 μ L water, add 200 μ L ethanol again, heating is dissolved it fully and is cooled to room temperature again and can forms gel.In addition, if change the order that solvent adds, can not need heating, can form above-mentioned gel at normal temperatures, for example in above-mentioned sample, add 200 μ L ethanol earlier, sample dissolves fully, adds 300 μ L water again, can form the oyster white gel immediately.
Compound
bBe the colloidal solid compound, the smell similar with Therapeutic Mineral Ice arranged, and can experience cooling effect when being applied on the skin.Compound
bAlso can only be in the certain mixed solvent of the ethanol of relative low toxicity and water the almost transparent gel of formation; Have hot reversible behavior equally, its gel is 56 ℃ to the transition temperature of colloidal sol, and minimum one-tenth gel strength is 12.5mg/mL; For example in containing sealed vial of 10mg sample; Add earlier 200 μ L water, add 50 μ L ethanol again, heating is dissolved it fully and is cooled to room temperature again and can forms gel.
Compound
cCan be dissolved in the common organic solvent, yet in water, can form hydrogel, and this hydrogel state is stable through heating refrigerative means; Can remain stationary a couple of days even several months; For example in containing sealed vial of 10mg sample, add 200 μ L water, heating is dissolved it fully and is cooled to the hydrogel that room temperature can form quite stable again; Its gel is 92 ℃ to the transition temperature of colloidal sol, and minimum one-tenth gel strength is 8.3mg/mL.Predict that this hydrogel can be applied to the cultivation of biomass cells, organizational project, aspects such as medicament slow release preferably.
Concrete gellifying property is seen table 1
The gellifying property of table 1. gelatinous cpd
| Solvent | Compound a | Compound b | Compound c |
| Water | Deposition | Deposition | Gel (8.3) |
| Methyl alcohol | Solution | Solution | Solution |
| Ethanol | Solution | Solution | Solution |
| Water+ethanol | Gel (11.8) | Gel (12.5) | Deposition |
| Water+methyl alcohol | Deposition | Deposition | Deposition |
Compound a (R: t-butyl carbamate, n=2), compound b (R: methyl aminoacetate, n=4), compound c (R: Padil, n=4); Gelatinous cpd is heated to dissolving (50-120 degree) postcooling to room temperature; In the parenthesis threshold concentration that forms gel, unit: mg/ml
2. the microscopic appearance of gelatinous cpd and accumulation mode
In order to obtain the microcosmic accumulation mode of gelatinous cpd, right
a,
b,
cThree kinds of gels that compound becomes have carried out the detection (seeing accompanying drawing) of ESEM (SEM) and X-ray powder diffraction (XRD).Can draw from SEM figure, these three kinds of gelatinous cpds are fibrous pattern, and compound
cFiber more carefully finer and close, this has verified the steady state that this hydrogel had.Draw from the simulation configuration of XRD figure spectrum binding molecule, three kinds of compounds all form fibrous-network structure through intermolecular non covalent bond effect makes solvent or water-setting gel, wherein compound
aMain through interaction of hydrogen bond between the amido linkage in the molecule and the formation of the hydrophobic interaction between menthyl one-dimentional structure, and compound
bWith
cAt first form dimer through the complementary hydrogen bond between aminocarboxylic acid or amino ester, dimer further forms one dimension aggregate (compound by intermolecular hydrophobic interaction mutual superposition again
a,
bWith
cThe model molecule accumulation mode see accompanying drawing).
Description of drawings
Fig. 1: three kinds of formed gel pictures of compound, compound
a(left side), compound
b(in), compound
c(right side);
Fig. 2: the ESEM of compound a (SEM) collection of illustrative plates;
Fig. 3: the X-ray powder diffraction of compound a (XRD) collection of illustrative plates;
Fig. 4: the ESEM of compound b (SEM) collection of illustrative plates;
Fig. 5: the X-ray powder diffraction of compound b (XRD) collection of illustrative plates;
Fig. 6: the ESEM of compound c (SEM) collection of illustrative plates;
Fig. 7: the X-ray powder diffraction of compound c (XRD) collection of illustrative plates;
Fig. 8: the model molecule accumulation mode of compound a;
Fig. 9: the model molecule accumulation mode of compound b;
Figure 10: the model molecule accumulation mode of compound c.
Embodiment
The formation and the preparation of the novel peppermint ester derivative of following further explain gellike compound, following all raw materials can be self-controls or commercially available.
Embodiment 1, gel factor a (R: t-butyl carbamate, synthetic and preparing gel n=2)
Get 7.5g Boc acid anhydrides and be dissolved in 100mL 1, in the 4-dioxane, be transferred in the constant pressure funnel; Slowly drop to the 100mL 1 that contains the 16.5g quadrol, in the 4-dioxane, after question response continues 22h; Solution is revolved dried, in residue, add 150mL water, then the elimination insolubles; With dichloromethane extraction three times, revolve the quadrol of dried Boc protection.The quadrol of getting 0.61g Boc protection adds the 15mL methylene dichloride in flask, transfer pH=7-8 with triethylamine; Compound chloroformic acid (left-handed) menthyl ester (95%) is dissolved in the 15mL methylene dichloride, is transferred in the constant pressure funnel, slowly be added drop-wise in the dichloromethane solution of quadrol of Boc protection; Reaction is spent the night, column chromatography for separation, revolve steam the pale powder product; 104 ℃ of fusing points
1H NMR (400 MHz, CDCl
3)
δ4.96 (s, 1H), 4.86 (s, 1H), 4.51 (s, 1H), 3.25 (s, 4H), 2.05 – 1.13 (m, 15H), 1.13 – 0.60 (m, 12H);
13C NMR (100MHz, CDCl
3)
δ157.02,156.46,79.50,74.67,47.44,41.47,41.27,34.23,31.41,28.64,28.32,28.12,26.32,23.60,22.07,20.82,16.53; HR-MS:365.2436 [M+Na]
+
Get compound L-lysine methyl ester dihydrochloride (1.273g, 0.00548mol) with triethylamine in flask, regulate pH=8-9, stirring at normal temperature 30min in the exsiccant chloroform; Again with compound chloroformic acid (left-handed) menthyl ester (1g 0.00457mol) is dissolved in the chloroform, is transferred to constant pressure funnel, dropwise adds reaction system, and reaction is spent the night, and column chromatography for separation is revolved to steam and obtained transparent gluey product, 75 ℃ of fusing points,
1H NMR (400 MHz, CDCl
3)
δ4.76 (s, 1H), 4.54 (s, 1H), 3.73 (s, 3H), 3.51 – 3.35 (m, 1H), 3.17 (d,
J=5.3 Hz, 2H), 2.03-1.91 (m, 2H), 1.75 – 1.25 (m, 10H), 1.10 – 0.79 (m, 12H);
13C NMR (100MHz, CDCl
3)
δ176.39,156.56,74.35,54.23,51.91,47.42,41.06,40.50,34.34,31.35,29.73,26.31,23.56,22.77,22.05,20.80,16.50; HR-MS:343.2614 [M+H]
+
Get compound
b(0.5g is 0.00147mol) in the 50mL tetrahydrofuran solvent, to wherein adding 20mL Lithium Hydroxide MonoHydrate (1.73g; 72.09mmol) aqueous solution, stirring at room reaction two days, ice bath is regulated the pH value to 2-3 down then; Revolve to steam and remove THF, separate out solid, suction filtration; Lyophilize gets the white powder product, 177 ℃ of fusing points
1H NMR (400MHz, DMSO-d
6)
δ13.7 (s, 1H), 8.27 (s, 3H), 7.02 (s, 1H), 4.39 (m, 1H), 3.84 (t, 1H), 2.94 (m, 2H), 1.87 (d,
J=7.9 Hz, 2H), 1.75 (s, 2H), 1.60-0.61 (m, 20H);
13C NMR (100MHz, DMSO)
δ171.37,156.59,73.22,52.36,47.43,41.91,34.39,31.44,30.08,29.41,26.26,23.65,22.47,22.09,21.07,16.80; HR-MS:329.2469 [M+H]
+
Claims (3)
1. menthyl ester derivative gel compound, it is characterized in that: compound all contains formamido-(left-handed) menthyl ester, and its general structure is following:
General molecular formula is:
[(C 10 H 19 O)-CONH-(CH 2 ) n -R]N=2-4 wherein, R represents t-butyl carbamate, methyl aminoacetate or Padil.
2. the preparation method of a menthyl ester derivative gel compound as claimed in claim 1; It is characterized in that concrete steps are: in methylene dichloride or chloroform, react the acyl derivative that obtains peppermint ester with chloroformic acid (left-handed) menthyl ester and L-lysine methyl ester or by the quadrol of the single protection of Boc, again deprotection or hydrolysis acquisition target compound.
3. a menthyl ester verivate as claimed in claim 1 forms the method for gel, it is characterized in that concrete steps are:
1) in gelatinous cpd, adds the mixed solvent of the second alcohol and water of certain volume ratio, be heated to dissolved state and be cooled to room temperature again and can form gel, perhaps add ethanol earlier it is dissolved fully, add entry more in certain proportion, can form gel under the room temperature;
2) in gelatinous cpd, add entry, be heated to dissolved state and be cooled to room temperature again and can form hydrogel.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2135516A1 (en) * | 2008-06-13 | 2009-12-23 | Symrise GmbH & Co. KG | Neo-menthyl derivatives as flavourings |
| CN102516346A (en) * | 2011-12-01 | 2012-06-27 | 复旦大学 | Organic micromolecule gel factor and application thereof |
-
2012
- 2012-09-21 CN CN2012103519798A patent/CN102827036A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2135516A1 (en) * | 2008-06-13 | 2009-12-23 | Symrise GmbH & Co. KG | Neo-menthyl derivatives as flavourings |
| CN102516346A (en) * | 2011-12-01 | 2012-06-27 | 复旦大学 | Organic micromolecule gel factor and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 《Bulletin of the Chemical Society of Japan》 19711231 Yamamoto, Hiroyuki和Hayakawa, Tadao Synthesis of poly[Nepsilon-(1-menthyloxycarbonyl)-L-lysine] and its secondary structure 1990-1992页 1-2 第44卷, 第7期 * |
| YAMAMOTO, HIROYUKI和HAYAKAWA, TADAO: "Synthesis of poly[Nε-(1-menthyloxycarbonyl)-L-lysine] and its secondary structure", 《BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN》, vol. 44, no. 7, 31 December 1971 (1971-12-31), pages 1990 - 1992 * |
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Application publication date: 20121219 |