CN110343131A - A kind of thio phosphatide cpd and preparation method thereof - Google Patents
A kind of thio phosphatide cpd and preparation method thereof Download PDFInfo
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- CN110343131A CN110343131A CN201910640421.3A CN201910640421A CN110343131A CN 110343131 A CN110343131 A CN 110343131A CN 201910640421 A CN201910640421 A CN 201910640421A CN 110343131 A CN110343131 A CN 110343131A
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- thio
- thioalkanoic
- methylene chloride
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- 125000000446 sulfanediyl group Chemical group *S* 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 102
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims abstract description 51
- 229960001231 choline Drugs 0.000 claims abstract description 51
- 238000006243 chemical reaction Methods 0.000 claims abstract description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
- 239000002253 acid Substances 0.000 claims abstract description 14
- 238000000746 purification Methods 0.000 claims abstract description 13
- KWVGIHKZDCUPEU-UHFFFAOYSA-N 2,2-dimethoxy-2-phenylacetophenone Chemical compound C=1C=CC=CC=1C(OC)(OC)C(=O)C1=CC=CC=C1 KWVGIHKZDCUPEU-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000011259 mixed solution Substances 0.000 claims abstract description 11
- 239000000047 product Substances 0.000 claims abstract description 7
- 150000001336 alkenes Chemical class 0.000 claims abstract description 5
- 239000012265 solid product Substances 0.000 claims abstract description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000741 silica gel Substances 0.000 claims abstract description 4
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 4
- 230000004913 activation Effects 0.000 claims description 10
- 238000004440 column chromatography Methods 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 5
- 238000005286 illumination Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 abstract description 4
- 230000010148 water-pollination Effects 0.000 abstract description 3
- 239000007800 oxidant agent Substances 0.000 abstract description 2
- 238000012650 click reaction Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- KOODSCBKXPPKHE-UHFFFAOYSA-N propanethioic s-acid Chemical compound CCC(S)=O KOODSCBKXPPKHE-UHFFFAOYSA-N 0.000 description 16
- 230000003647 oxidation Effects 0.000 description 14
- 238000007254 oxidation reaction Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 239000007787 solid Substances 0.000 description 9
- 150000001875 compounds Chemical group 0.000 description 8
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 8
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- AFFLGGQVNFXPEV-UHFFFAOYSA-N 1-decene Chemical compound CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 4
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 4
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 4
- YEUAOTZWAWUYBH-UHFFFAOYSA-N hexanethioic s-acid Chemical compound CCCCCC(S)=O YEUAOTZWAWUYBH-UHFFFAOYSA-N 0.000 description 4
- DXPLUGSEYNNZQT-UHFFFAOYSA-N 2-methyltetradecanethioic s-acid Chemical compound CCCCCCCCCCCCC(C)C(S)=O DXPLUGSEYNNZQT-UHFFFAOYSA-N 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000000693 micelle Substances 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- QWDDFCKIEJCEMF-UHFFFAOYSA-N propane-1,2,3-triol 2-(trimethylazaniumyl)ethyl hydrogen phosphate Chemical compound OCC(O)CO.C[N+](C)(C)CCOP(O)([O-])=O QWDDFCKIEJCEMF-UHFFFAOYSA-N 0.000 description 2
- MVCPDOUDYOUTKS-UHFFFAOYSA-N propanedithioic acid Chemical compound CCC(S)=S MVCPDOUDYOUTKS-UHFFFAOYSA-N 0.000 description 2
- -1 thio phosphorus Chemical compound 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- HFDVRLIODXPAHB-UHFFFAOYSA-N 1-tetradecene Chemical group CCCCCCCCCCCCC=C HFDVRLIODXPAHB-UHFFFAOYSA-N 0.000 description 1
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- GQEZCXVZFLOKMC-UHFFFAOYSA-N n-alpha-hexadecene Natural products CCCCCCCCCCCCCCC=C GQEZCXVZFLOKMC-UHFFFAOYSA-N 0.000 description 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses a kind of thio phosphatide cpds and preparation method thereof, its preparation step is as follows: 1) 10~12 mMs of the positive alkene of 1-, 10 mMs of the positive alkanoic acid of 1- sulfydryl are dissolved in methylene chloride, it is added 0.05~0.5 mM 2,2- dimethoxy -2- phenyl acetophenone causes click-reaction, after the reaction was completed, thioalkanoic is obtained with silica gel column chromatogram separating purification；2) above-mentioned thioalkanoic product is dissolved in methylene chloride, and N is added, and N'- carbonyl dimidazoles activate 0.5~4 hour；The dimethyl sulfoxide mixed solution that 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene and choline glycerophosphatide is added isolates and purifies to obtain white solid product thioalkanoic choline glycerophosphatide after the reaction was completed.Containing the thioether bond for being easy to aoxidize in thio phosphatide cpd structure provided by the invention, the quick oxidative deformation in Oxidant has better hydrophily.
Description
Technical field
The present invention relates to a kind of thio phosphatide cpds and preparation method thereof, belong to phosphatide cpd technical field.
Background technique
Phosphatide is a kind of important surfactant, and prepares liposome, nano-micelle, microemulsion, solid lipid and receive
The important materials of the pharmaceutical carriers such as the grain of rice.The degradation of common phosphatide depends on the hydrolysis of ester bond, and assemble nanometer carrier is caused to be not easy
Cracking.The not special function of common phosphatide, limits its application range, especially can not constructing function nanometer
Grain.
Peroxy radical concentration is much higher than normal tissue in inflammatory tissue, tumor tissues especially tumour cell, utilizes it
Microenvironment can promote the molecular oxidation containing oxidation-sensitive key to cause, and hydrophily enhances or carrier cracks.
In view of above-mentioned, need to invent a kind of phosphatide and preparation method thereof with oxidation-sensitive function.
Summary of the invention
The purpose of the present invention is to provide a kind of thio phosphatide cpds and preparation method thereof, and the phosphatide cpd has
Oxidation-sensitive function is a kind of oxidation response phosphatide cpd containing thioether bond.
The technical solution of the present invention is to provide a kind of thio phosphatide cpd, the general structure of the phosphatide cpd such as formulas
1:
In formula, m is 2~9 positive integer, and n is 5~15 positive integer.
The present invention also provides a kind of preparation methods of thio phosphatide cpd, include the following steps:
1) 10~12 mMs of the positive alkene of 1-, 10 mMs of the positive alkanoic acid of 1- sulfydryl, are dissolved in 100-150 milliliters of methylene chloride
In, 0.05~0.5 mM of 2,2- dimethoxy -2- phenyl acetophenone is added, illumination causes click chemistry at 20~50 DEG C
Reaction 1~6 hour, revolving remove methylene chloride, obtain thioalkanoic with silica gel column chromatogram separating purification,
2), above-mentioned thioalkanoic is dissolved in 50 milliliters of methylene chloride, and N is added, and the activation 0.5~4 of N'- carbonyl dimidazoles is small
When；The dimethyl sulfoxide mixed solution 20-40 of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene and choline glycerophosphatide is added
Milliliter；It is stirred to react at 20~60 DEG C 3~24 hours；After the reaction was completed, it isolates and purifies to obtain white solid product thioalkanoic
Choline glycerophosphatide.
Wherein:
Thioalkanoic described in step 2), N, N'- carbonyl dimidazoles, 11 carbon -7- of 1,8- diazabicyclo [5.4.0]
The molar ratio of alkene and choline glycerophosphatide is 2:1~3:1~1.5:0.5~1.5.
It isolates and purifies to obtain product thioalkanoic choline glycerophosphatide described in step 2), is directed to after the reaction was completed anti-
It answers and distilled water dissolution is added in liquid, methylene chloride extraction is then added, uses column chromatography separating purification after extract liquor concentration.
Beneficial effects of the present invention: compared with prior art, present invention has the advantage that thio phosphorus provided by the invention
Containing the thioether bond for being easy to aoxidize in compound structure, the quick oxidative deformation in Oxidant has preferably hydrophilic
Property.
Detailed description of the invention
Fig. 1 is thio phosphatide cpd synthetic route chart in the present invention；
Fig. 2 is double in the present invention-n-tetradecane base propane thioic acid choline glycerophosphatide 14S3-PC after hydrogen peroxide oxidation
The high resolution mass spectrum figure of product；
Fig. 3 be double in the present invention-n-tetradecane base propane thioic acid choline glycerophosphatide 14S3-PC through hydrogen peroxide oxidation before
Nmr spectrum afterwards.
Specific embodiment
Further details of the technical solution of the present invention with embodiment with reference to the accompanying drawings of the specification, embodiment into
One step illustrates the present invention, but the present invention is not limited to following embodiments.
A kind of thio phosphatide cpd, the general structure of the phosphatide cpd such as formula 1:
In formula, m is 2~9 positive integer, and n is 5~15 positive integer.
Preparation method includes the following steps the (part pair-thio nalka acid glycerol phosphocholine synthetic route of alkyl two
As shown in Figure 1):
1), 10~12 mMs of the positive alkene of 1-, 10 mMs of the positive alkanoic acid of 1- sulfydryl are dissolved in 100 milliliters of methylene chloride,
0.05~0.5 mM of 2,2- dimethoxy -2- phenyl acetophenone is added, illumination, which causes, at 20~50 DEG C clicks chemical reaction
1-6 hours, revolving removed methylene chloride, obtained thioalkanoic with silica gel column chromatogram separating purification；
2), above-mentioned thioalkanoic is dissolved in 50 milliliters of methylene chloride, and N is added, and the activation 0.5~4 of N'- carbonyl dimidazoles is small
When, 30 milli of dimethyl sulfoxide mixed solution of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene and choline glycerophosphatide is added
It rises, is stirred to react at 20~60 DEG C 3~24 hours；After the reaction was completed, it isolates and purifies to obtain white solid product thioalkanoic sweet
Oleophosphoric acid choline；Wherein, thioalkanoic, N, N'- carbonyl dimidazoles, 1,8- diazabicyclo [5.4.0], 11 carbon -7- alkene and sweet
The molar ratio of oleophosphoric acid choline is 2:1~3:1~1.5:0.5~1.5.
The following are portion of reagent code names used in preparation process:
CDI N, N'- carbonyl dimidazoles,
11 carbon -7- alkene of DBU 1,8- diazabicyclo [5.4.0],
GPC choline glycerophosphatide,
DMPA 2,2- dimethoxy -2- phenyl acetophenone,
The thio nalka acid glycerol phosphocholine product of double-alkyl is denoted as XSY-PC, such as: double-n-decane base propane thioic acid
Choline glycerophosphatide is denoted as 10S3-PC.
Embodiment 1
Double-n-decane base propane thioic acid choline glycerophosphatide:
A kind of phosphatide cpd, the compound be it is double-(synthetic route is shown in figure to n-decane base propane thioic acid choline glycerophosphatide
1, m takes 2, n to take 9) in formula, structure are as follows:
Its preparation step is as follows:
1), 10 mMs of 1- decene, 10 mMs of 1- mercaptopropionic acid be dissolved in 100 milliliters of methylene chloride of solvent, be added
0.05 mM of 2,2- dimethoxy -2- phenyl acetophenone (DMPA), 365 nano-ultraviolet lights are illuminated the way at room temperature, and to send out click chemistry anti-
It answers 1 hour, evaporation of solvent, is isolated and purified with silica gel column chromatography (eluent: methylene chloride/methanol, volume ratio 20/1)
To thioalkanoic；
2), above-mentioned thioalkanoic is dissolved in 100 milliliters of methylene chloride, and N, 20 mMs of N'- carbonyl dimidazoles activation 1 are added
Hour, 10 mMs and 5 mMs of choline glycerophosphatide of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene of 30 millis are added
Dimethyl sulfoxide mixed solution is risen, reaction 24 hours is stirred at room temperature；After the reaction was completed, column chromatography separating purification obtains white solid production
Object is -2.1 grams of choline glycerophosphatide of n-decane base propane thioic acid double, is denoted as 10S3-PC.
Embodiment 2
Double-dodecyl propane thioic acid choline glycerophosphatide:
A kind of phosphatide cpd, the compound be it is double-dodecyl propane thioic acid choline glycerophosphatide (be shown in by synthetic route
Fig. 1, m takes 2, n to take 11) in formula, structure are as follows:
Its preparation step is as follows:
1), 12 mMs of 1- laurylene, 10 mMs of 1- mercaptopropionic acid be dissolved in 150 milliliters of methylene chloride of solvent, be added
0.05 mM of 2,2- dimethoxy -2- phenyl acetophenone, 365 nano-ultraviolet lights are illuminated the way at room temperature, and to send out click chemistry reaction 2 small
When, evaporation of solvent isolates and purifies to obtain thio with silica gel column chromatography (eluent: methylene chloride/methanol, volume ratio 20/1)
Alkanoic acid；
2), above-mentioned thioalkanoic product is dissolved in 150 milliliters of methylene chloride, be added N, 20 mMs of N'- carbonyl dimidazoles
Activation 1 hour is added 10 mMs and 5 mMs of choline glycerophosphatide of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene
Reaction 12 hours is stirred at room temperature in 40 milliliters of dimethyl sulfoxide mixed solutions；After the reaction was completed, it is solid to obtain white for column chromatography separating purification
Body product pair -2.9 grams of dodecyl propane thioic acid choline glycerophosphatide, is denoted as 12S3-PC.
Embodiment 3
Double-n-tetradecane base propane thioic acid choline glycerophosphatide:
A kind of phosphatide cpd, the compound be it is double-n-tetradecane base propane thioic acid choline glycerophosphatide (be shown in by synthetic route
Fig. 1, m takes 2, n to take 13) in formula, structure are as follows:
Its preparation step is as follows:
1), 12 mMs of 1-tetradecylene, 10 mMs of 1- mercaptopropionic acid be dissolved in 150 milliliters of methylene chloride of solvent, be added
0.5 mM of 2,2- dimethoxy -2- phenyl acetophenone, 365 nano-ultraviolet lights are illuminated the way at room temperature, and to send out click chemistry reaction 2 small
When, evaporation of solvent isolates and purifies to obtain thio with silica gel column chromatography (eluent: methylene chloride/methanol, volume ratio 20/1)
Alkanoic acid；
2), above-mentioned thioalkanoic is dissolved in 150 milliliters of methylene chloride, and N, 30 mMs of N'- carbonyl dimidazoles activation 1 are added
Hour, 10 mMs and 8 mMs of choline glycerophosphatide of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene of 40 millis are added
Dimethyl sulfoxide mixed solution is risen, reaction 6 hours is stirred at room temperature；After the reaction was completed, column chromatography separating purification obtains white solid production
Object pair -3.5 grams of dodecyl propane thioic acid choline glycerophosphatide, is denoted as 14S3-PC.
Embodiment 4
To double-alkyl dithiopropionic acid choline glycerophosphatide that Examples 1 to 3 is prepared, using fluorescence probe
Method measurement pair-alkyl dithiopropionic acid choline glycerophosphatide critical micelle concentration (CMC), as a result see the table below；Using showing residual quantity
Heat scan measures its thermal property (5 DEG C/min of heating rate, -30 DEG C to 80 DEG C of temperature range), obtains phase transition temperature Tc and is listed in table 1
In.
The critical micelle concentration (CMC) and phase transition temperature (Tc) of table 1, double-alkyl propane thioic acid choline glycerophosphatide
| Thio phosphatide | CMC/μgmL-1 | Tc/℃ |
| 10S3-PC | 3.39 | 16.13 |
| 12S3-PC | 2.14 | 33.25 |
| 14S3-PC | 0.83 | 46.02 |
Embodiment 5
The thio caproic acid choline glycerophosphatide of double-n-decane base:
A kind of phosphatide cpd, the compound are double-thio caproic acid choline glycerophosphatide of n-decane base, structure are as follows:
Its preparation step is as follows:
1), 11 mMs of 1- decene, 10 mMs of ω-mercaptohexanoic acid be dissolved in 100 milliliters of methylene chloride of solvent, be added
0.1 mM of 2,2- dimethoxy -2- phenyl acetophenone, 365 nano-ultraviolet lights are illuminated the way at room temperature, and to send out click chemistry reaction 6 small
When, evaporation of solvent isolates and purifies to obtain thio with silica gel column chromatography (eluent: methylene chloride/methanol, volume ratio 10/1)
Alkanoic acid；
2), above-mentioned thioalkanoic is dissolved in 100 milliliters of methylene chloride, and N, 20 mMs of N'- carbonyl dimidazoles activation 1 are added
Hour, 10 mMs and 5 mMs of choline glycerophosphatide of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene of 20 millis are added
Dimethyl sulfoxide mixed solution is risen, reaction 24 hours is stirred at room temperature；After the reaction was completed, column chromatography separating purification obtains white solid production
Object pair -2.4 grams of the thio caproic acid choline glycerophosphatide of n-decane base, is denoted as 10S6-PC.
Embodiment 6
The thio capric acid choline glycerophosphatide of double-n-hexane base:
A kind of phosphatide cpd, the compound are double-thio capric acid choline glycerophosphatide of n-hexane base, structure are as follows:
Its preparation step is as follows:
1), 11 mMs of 1- hexene, ω -10 mMs of sulfydryl capric acid are dissolved in 100 milliliters of methylene chloride of solvent, are added
0.1 mM of 2,2- dimethoxy -2- phenyl acetophenone, 365 nano-ultraviolet lights are illuminated the way at room temperature, and to send out click chemistry reaction 6 small
When, evaporation of solvent isolates and purifies to obtain thio with silica gel column chromatography (eluent: methylene chloride/methanol, volume ratio 10/1)
Alkanoic acid；
2), above-mentioned thioalkanoic is dissolved in 100 milliliters of methylene chloride, and N, 20 mMs of N'- carbonyl dimidazoles activation 1 are added
Hour, 10 mMs and 5 mMs of choline glycerophosphatide of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene of 20 millis are added
Dimethyl sulfoxide mixed solution is risen, reaction 24 hours is stirred at room temperature；After the reaction was completed, column chromatography separating purification obtains white solid production
Object pair -2.4 grams of the thio capric acid choline glycerophosphatide of n-hexane base, is denoted as 6S10-PC.
Embodiment 7
The thio caproic acid choline glycerophosphatide of double-n-hexane base:
A kind of phosphatide cpd, the compound are double-thio caproic acid choline glycerophosphatide of n-hexane base, structure are as follows:
Its preparation step is as follows:
1), 11 mMs of 1- hexene, 10 mMs of ω-mercaptohexanoic acid be dissolved in 100 milliliters of methylene chloride of solvent, be added
0.1 mM of 2,2- dimethoxy -2- phenyl acetophenone, 365 nano-ultraviolet lights are illuminated the way at room temperature, and to send out click chemistry reaction 6 small
When, evaporation of solvent isolates and purifies to obtain thio with silica gel column chromatography (eluent: methylene chloride/methanol, volume ratio 10/1)
Alkanoic acid；
2), above-mentioned thioalkanoic is dissolved in 100 milliliters of methylene chloride, and N, 20 mMs of N'- carbonyl dimidazoles activation 1 are added
Hour, 10 mMs and 5 mMs of choline glycerophosphatide of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene of 20 millis are added
Dimethyl sulfoxide mixed solution is risen, reaction 24 hours is stirred at room temperature；After the reaction was completed, column chromatography separating purification obtains white solid production
Object pair -2.6 grams of the thio caproic acid choline glycerophosphatide of n-hexane base, is denoted as 6S6-PC.
Embodiment 8
Double-n-hexadecyl propane thioic acid choline glycerophosphatide:
A kind of phosphatide cpd, the compound be it is double-n-hexadecyl propane thioic acid choline glycerophosphatide (be shown in by synthetic route
Fig. 1, m takes 2, n to take 15) in formula, structure are as follows:
Its preparation step is as follows:
1), 12 mMs of 1- hexadecylene, 10 mMs of 1- mercaptopropionic acid be dissolved in 150 milliliters of methylene chloride of solvent, be added
0.5 mM of 2,2- dimethoxy -2- phenyl acetophenone, 365 nano-ultraviolet lights are illuminated the way at room temperature, and to send out click chemistry reaction 2 small
When, evaporation of solvent isolates and purifies to obtain thio with silica gel column chromatography (eluent: methylene chloride/methanol, volume ratio 20/1)
Alkanoic acid；
2), above-mentioned thioalkanoic is dissolved in 150 milliliters of methylene chloride, and N, 30 mMs of N'- carbonyl dimidazoles activation 1 are added
Hour, 10 mMs and 8 mMs of choline glycerophosphatide of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene of 40 millis are added
Dimethyl sulfoxide mixed solution is risen, is stirred to react 24 hours under 60 degrees Celsius；After the reaction was completed, column chromatography separating purification obtains white
Solid product pair -3.2 grams of dodecyl propane thioic acid choline glycerophosphatide, is denoted as 16S3-PC.
Embodiment 9
The oxidation sensitive of double-n-tetradecane base propane thioic acid choline glycerophosphatide:
The aqueous solution 9 for double-n-tetradecane base propane thioic acid choline glycerophosphatide 14S3-PC that embodiment 3 is prepared
Milliliter (concentration 2mg/mL), being added 1 milliliter of aqueous hydrogen peroxide solution makes its final concentration reach 20mM, and it is small to be incubated for 24 altogether at 37 DEG C
When；Freeze-drying, a little solid are dissolved in deuterated dimethyl sulfoxide, use1H-NMR measurement；A little solid is separately taken to be divided with high resolution mass spectrum
Analysis, is as a result shown in Fig. 2.
By high resolution mass spectrum Fig. 2 as it can be seen that 858.52 and 880.50 correspond respectively to point that 14S3-PC sulfide oxidation is sulfoxide
(the m/z [M+H] of theoretical value 858.53 at daughter ion peak+) and 880.52 (m/z [M+Na]+)。
Double-n-tetradecane base propane thioic acid choline glycerophosphatide 14S3-PC oxidation front and back1H-NMR figure is shown in Fig. 3 a and b；
The results show that the chemical shift for the methylene hydrogen being connected before oxidation with sulphur is 2.60ppm (position 1), it is moved to after oxidation
3.03ppm (position 1 '), this is because sulfide oxidation is caused by sulfoxide；The result shows that 14S3-PC is through H2O2It is oxidized into sulfoxide
Structure, is shown in Fig. 3, and hydrophily improves.Therefore, 14S3-PC has oxidation sensitive.
Above-described embodiment is only the preferred embodiment of the present invention, it should be pointed out that: for the ordinary skill of the art
For personnel, without departing from the principle of the present invention, several improvement and equivalent replacement can also be made, these are to the present invention
Claim improve with the technical solution after equivalent replacement, each fall within protection scope of the present invention.
Claims (4)
1. a kind of thio phosphatide cpd, it is characterised in that: the general structure of the phosphatide cpd such as formula 1:
In formula, m is 2~9 positive integer, and n is 5~15 positive integer.
2. a kind of preparation method of thio phosphatide cpd as described in claim 1, it is characterised in that: the preparation method includes
Following steps:
1), 10~12 mMs of the positive alkene of 1-, 10 mMs of the positive alkanoic acid of 1- sulfydryl are dissolved in 100-150 milliliters of methylene chloride,
0.05~0.5 mM of 2,2- dimethoxy -2- phenyl acetophenone is added, illumination, which causes, at 20~50 DEG C clicks chemical reaction
1~6 hour, revolving removed methylene chloride, obtained thioalkanoic with silica gel column chromatogram separating purification；
2), thioalkanoic obtained above is dissolved in 50 milliliters of methylene chloride, N, N'- carbonyl dimidazoles activation 0.5~4 is added
Hour；Add the dimethyl sulfoxide mixed solution of 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene and choline glycerophosphatide
It 20-40 milliliters, is stirred to react at 20~60 DEG C 3~24 hours；After the reaction was completed, it isolates and purifies to obtain white solid product
Thioalkanoic choline glycerophosphatide.
3. a kind of preparation method of thio phosphatide cpd as claimed in claim 2, it is characterised in that: described in step 2)
Thioalkanoic, N, mole of N'- carbonyl dimidazoles, 1,8- diazabicyclo [5.4.0] 11 carbon -7- alkene and choline glycerophosphatide
Than for 2:1~3:1~1.5:0.5~1.5.
4. a kind of preparation method of thio phosphatide cpd as claimed in claim 2, it is characterised in that: divide described in step 2)
From the product thioalkanoic choline glycerophosphatide that purifying obtains, it is water-soluble to be directed to addition distillation in reaction solution after the reaction was completed
Then solution is added methylene chloride extraction, uses column chromatography separating purification after extract liquor concentration.
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| CN1675229A (en) * | 2002-06-20 | 2005-09-28 | Icvec有限公司 | Sulfur-containing phospholipid derivatives |
| CN108489953A (en) * | 2018-05-10 | 2018-09-04 | 长春理工大学 | A kind of preparation method of in-situ modification paper substrate nitro explosive fluorescent sensing material |
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| CN1675229A (en) * | 2002-06-20 | 2005-09-28 | Icvec有限公司 | Sulfur-containing phospholipid derivatives |
| CN108489953A (en) * | 2018-05-10 | 2018-09-04 | 长春理工大学 | A kind of preparation method of in-situ modification paper substrate nitro explosive fluorescent sensing material |
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