CN113072602B - Phenolic acid glycosyl ester and preparation method thereof - Google Patents
Phenolic acid glycosyl ester and preparation method thereof Download PDFInfo
- Publication number
- CN113072602B CN113072602B CN202110252991.2A CN202110252991A CN113072602B CN 113072602 B CN113072602 B CN 113072602B CN 202110252991 A CN202110252991 A CN 202110252991A CN 113072602 B CN113072602 B CN 113072602B
- Authority
- CN
- China
- Prior art keywords
- reaction
- ester
- phenolic acid
- channel
- microchannel
- 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.)
- Active
Links
- -1 Phenolic acid glycosyl ester Chemical class 0.000 title claims abstract description 89
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims abstract description 156
- 150000002148 esters Chemical class 0.000 claims abstract description 38
- 150000007965 phenolic acids Chemical class 0.000 claims abstract description 32
- 239000003054 catalyst Substances 0.000 claims abstract description 22
- 150000007530 organic bases Chemical class 0.000 claims abstract description 22
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 18
- 239000008103 glucose Substances 0.000 claims abstract description 18
- 229930006000 Sucrose Natural products 0.000 claims abstract description 17
- 239000005720 sucrose Substances 0.000 claims abstract description 17
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229960002442 glucosamine Drugs 0.000 claims abstract description 16
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 15
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims abstract description 14
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims description 23
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 18
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 16
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 16
- AUJXJFHANFIVKH-GQCTYLIASA-N trans-methylferulate Chemical compound COC(=O)\C=C\C1=CC=C(O)C(OC)=C1 AUJXJFHANFIVKH-GQCTYLIASA-N 0.000 claims description 16
- BVWTXUYLKBHMOX-UHFFFAOYSA-N methyl vanillate Chemical compound COC(=O)C1=CC=C(O)C(OC)=C1 BVWTXUYLKBHMOX-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 11
- 239000007810 chemical reaction solvent Substances 0.000 claims description 10
- FBSFWRHWHYMIOG-UHFFFAOYSA-N methyl 3,4,5-trihydroxybenzoate Chemical compound COC(=O)C1=CC(O)=C(O)C(O)=C1 FBSFWRHWHYMIOG-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- CUFLZUDASVUNOE-UHFFFAOYSA-N Protocatechuic acid methyl ester Natural products COC(=O)C1=CC=C(O)C(O)=C1 CUFLZUDASVUNOE-UHFFFAOYSA-N 0.000 claims description 8
- AUJXJFHANFIVKH-UHFFFAOYSA-N methyl cis-ferulate Natural products COC(=O)C=CC1=CC=C(O)C(OC)=C1 AUJXJFHANFIVKH-UHFFFAOYSA-N 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 8
- 239000011347 resin Substances 0.000 claims description 7
- 229920005989 resin Polymers 0.000 claims description 7
- 235000014633 carbohydrates Nutrition 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 230000007246 mechanism Effects 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 3
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 claims description 2
- ACEAELOMUCBPJP-OWOJBTEDSA-N (e)-3-(3,4,5-trihydroxyphenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-OWOJBTEDSA-N 0.000 claims description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 claims description 2
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims description 2
- FVKFHMNJTHKMRX-UHFFFAOYSA-N 3,4,6,7,8,9-hexahydro-2H-pyrimido[1,2-a]pyrimidine Chemical group C1CCN2CCCNC2=N1 FVKFHMNJTHKMRX-UHFFFAOYSA-N 0.000 claims description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims description 2
- NITWSHWHQAQBAW-QPJJXVBHSA-N Methyl 4-hydroxy cinnamate Natural products COC(=O)\C=C\C1=CC=C(O)C=C1 NITWSHWHQAQBAW-QPJJXVBHSA-N 0.000 claims description 2
- NITWSHWHQAQBAW-UHFFFAOYSA-N MpCA Natural products COC(=O)C=CC1=CC=C(O)C=C1 NITWSHWHQAQBAW-UHFFFAOYSA-N 0.000 claims description 2
- PVRDAVSDHWPSOF-UHFFFAOYSA-N Vanillic acid methyl ester Natural products COC(=O)C(=O)C1=CC=C(O)C(OC)=C1 PVRDAVSDHWPSOF-UHFFFAOYSA-N 0.000 claims description 2
- MAEVSPLUELJOMM-UHFFFAOYSA-N caffeic acid methyl ester Natural products COC(=O)C=CC1=CC=C(O)C=C1O MAEVSPLUELJOMM-UHFFFAOYSA-N 0.000 claims description 2
- JHLPYWLKSLVYOI-SNAWJCMRSA-N methyl (e)-3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC(OC)=C(O)C(OC)=C1 JHLPYWLKSLVYOI-SNAWJCMRSA-N 0.000 claims description 2
- OCNYGKNIVPVPPX-HWKANZROSA-N methyl caffeate Chemical compound COC(=O)\C=C\C1=CC=C(O)C(O)=C1 OCNYGKNIVPVPPX-HWKANZROSA-N 0.000 claims description 2
- ZMXJAEGJWHJMGX-UHFFFAOYSA-N methyl syringate Chemical compound COC(=O)C1=CC(OC)=C(O)C(OC)=C1 ZMXJAEGJWHJMGX-UHFFFAOYSA-N 0.000 claims description 2
- YFBSBLHMAWUCJB-UHFFFAOYSA-N methyl syringate Natural products COc1cc(cc(OC)c1O)C(=O)OO YFBSBLHMAWUCJB-UHFFFAOYSA-N 0.000 claims description 2
- JHLPYWLKSLVYOI-UHFFFAOYSA-N trans-Sinapic acid methylester Natural products COC(=O)C=CC1=CC(OC)=C(O)C(OC)=C1 JHLPYWLKSLVYOI-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 14
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 12
- 229930195729 fatty acid Natural products 0.000 abstract description 12
- 239000000194 fatty acid Substances 0.000 abstract description 12
- 230000006937 anti-inflammatory bioactivity Effects 0.000 abstract description 6
- 230000002829 reductive effect Effects 0.000 abstract description 6
- 238000007086 side reaction Methods 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 231100000245 skin permeability Toxicity 0.000 abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 75
- 239000000126 substance Substances 0.000 description 36
- 238000004458 analytical method Methods 0.000 description 22
- 238000012360 testing method Methods 0.000 description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
- 241000894006 Bacteria Species 0.000 description 15
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
- 241000191967 Staphylococcus aureus Species 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 12
- 229960002216 methylparaben Drugs 0.000 description 12
- 230000005311 nuclear magnetism Effects 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 11
- 238000001514 detection method Methods 0.000 description 11
- 238000011156 evaluation Methods 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 238000000105 evaporative light scattering detection Methods 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 238000001819 mass spectrum Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 230000001580 bacterial effect Effects 0.000 description 8
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 8
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 7
- JTLOUXXZZFFBBW-UHFFFAOYSA-N isoferulic acid methyl ester Natural products COC(=O)C=CC1=CC=C(OC)C(O)=C1 JTLOUXXZZFFBBW-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- 238000000746 purification Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- IBKQQKPQRYUGBJ-UHFFFAOYSA-N methyl gallate Natural products CC(=O)C1=CC(O)=C(O)C(O)=C1 IBKQQKPQRYUGBJ-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- GZCGUPFRVQAUEE-VANKVMQKSA-N aldehydo-L-glucose Chemical compound OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-VANKVMQKSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002190 fatty acyls Chemical group 0.000 description 1
- 150000002301 glucosamine derivatives Chemical class 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000001474 liquid chromatography-evaporative light scattering detection Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003445 sucroses Chemical class 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- 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
- C07H13/08—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 directly attached to carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention provides phenolic acid glycosyl ester and a preparation method thereof, wherein the structure of the phenolic acid glycosyl ester is shown as a formula (I), a formula (II) or a formula (III). The phenolic acid glycosyl ester is obtained by derivatizing glucose, glucosamine or sucrose by phenolic acid, and has more excellent antibacterial and anti-inflammatory biological activity, high skin permeability and high water solubility compared with the existing glycosyl fatty acid ester. The phenolic acid base sugar ester preparation method utilizes the saccharide compound and the phenolic acid compound to prepare the phenolic acid base sugar ester under the catalysis of the organic base catalyst, so that side reaction can be reduced, conversion rate can be improved, product purity can be improved, and the preparation method is carried out in a reaction microchannel.
Description
Technical Field
The invention relates to a glycosyl fatty acid ester compound, in particular to a phenolic acid glycosyl ester and a preparation method thereof.
Background
The glycosyl fatty acid ester is a biological functional chemical, is 100% natural in source, nontoxic and easy to biodegrade, has excellent surface activity, antibacterial and anti-inflammatory bioactivity and the like, such as C8-C16 fatty acid sucrose monoester/diester, sucrose sulfate, phenyl carboxylic acid sucrose ester derivative and the like, but the antibacterial and anti-inflammatory bioactivity of the existing glycosyl fatty acid ester needs to be improved.
Typically, glycosyl fatty acid esters are prepared from sugar and fatty acid (esters) or fatty acid chlorides by esterification or transesterification, with the most common synthetic strategies being chemical and biological. The chemical method is to co-operate in DMSO, DMF and depthSolvent systems such as melt solvents (DES) and the like or solvent-free conditions are adopted by KOH and K 2 CO 3 And the like, or organic metals such as Sn are adopted to catalyze the reaction of the carbohydrate and the fatty acid ester/fatty acyl chloride to synthesize the glycosyl fatty acid ester, and the mass transfer and the effective contact probability of molecules in the reaction process are low, the selective esterification of a plurality of hydroxyl groups is difficult to control due to the intrinsic characteristics of large difference of the molecular polarities of the carbohydrate and the fatty acid ester, similar activity of a plurality of hydroxyl groups of the sugar molecules and the like, so that the chemical method has the defects of serious side reaction, low reaction yield, poor regioselectivity and stereoselectivity of the carbohydrate ester product, complex separation and purification process, more pollution waste emission and the like.
Disclosure of Invention
The invention aims to overcome the defects existing in the prior art and provide phenolic acid glycosyl ester and a preparation method thereof.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: a phenolic acid glycosyl ester, wherein the structure of the phenolic acid glycosyl ester is shown as a formula (I), a formula (II) or a formula (III);
the substituent R is
The substituent R1 is hydroxyl, and the substituent R2 and R3 are hydroxyl or alkoxy.
The inventors derived glucose, glucosamine or sucrose from phenolic acid to obtain the above phenolic acid-based sugar ester, found that the above phenolic acid-based sugar ester has superior antibacterial and anti-inflammatory bioactivity, high skin permeability and high water solubility compared with the existing glycosyl fatty acid ester, and the phenolic acid-based sugar ester represented by formula (II) or (III) has better antibacterial property compared with formula (I).
Preferably, in the substituent group R, the substituent group R1 and the ester group are located at the para position of the phenyl group.
Preferably, the substituent R is
The inventor found through research that the phenyl on the substituent group R of the phenolic acid glycosyl ester has more than two substituent groups and at least comprises one hydroxyl group, and has more excellent anti-inflammatory biological activity.
Preferably, at least one of the substituents R2, R3 is hydroxy.
Preferably, the alkoxy group is methoxy.
The invention also provides a preparation method of any of the phenolic acid glycosyl esters, which comprises the following steps: the saccharide compound, phenolic acid compound and organic base catalyst are mixed and reacted in the reaction solvent at 110-140 deg.c.
The method utilizes the saccharide compound and the phenolic acid compound to prepare the phenolic acid-based sugar ester under the catalysis of the organic base catalyst, so that side reaction can be reduced, the conversion rate can be improved, and the purity of the product can be improved.
Preferably, the molar ratio of the saccharide compound and the phenolic acid compound is 1: (0.5-2).
Preferably, the saccharide compound is glucose, glucosamine or sucrose; the phenolic acid compound is methyl p-hydroxybenzoate, protocatechuic acid methyl ester, gallic acid methyl ester, methyl vanillic acid methyl ester, methyl syringate, 4-hydroxy cinnamic acid methyl ester, caffeic acid methyl ester, 3,4, 5-trihydroxy cinnamic acid methyl ester, ferulic acid methyl ester or sinapic acid methyl ester; the organic base catalyst is 1,5, 7-triazabicyclo [4.4.0] dec-5-ene, 1, 8-diazabicyclo undec-7-ene and 1, 5-diazabicyclo [4.3.0] non-5-ene, and the reaction solvent is dimethyl sulfoxide or N, N-dimethylformamide.
When the saccharide compound is glucose, preparing a compound shown in a formula (I); when the saccharide compound is glucosamine, preparing a compound shown in a formula (II); when the saccharide compound is sucrose, the compound represented by the formula (III) is prepared.
Preferably, the saccharide compound is glucosamine or sucrose.
The phenolic acid-based glucosamine ester and the phenolic acid-based sucrose ester have better antibacterial performance compared with the phenolic acid-based glucosamine ester.
Preferably, the reaction is performed in a reaction microchannel, a mixed solution of a carbohydrate compound and a reaction solvent, a mixed solution of a phenolic acid compound and the reaction solvent flows through the reaction microchannel, the reaction microchannel is a hollow pipeline, the reaction microchannel is provided with a liquid inlet and a liquid outlet, a deflector is arranged in the reaction microchannel, the deflector is arranged along the liquid flowing direction of the reaction microchannel, a plurality of netlike reaction plates distributed and arranged are fixed on the surface of the deflector and the inner surface of the reaction microchannel, the netlike reaction plates are obliquely fixed on the surface of the deflector or the inner surface of the reaction microchannel, an organic base catalyst is bonded on the netlike reaction plates, and the organic base catalyst is connected to resin through C-N or C-C bonds and is attached on the surface of the netlike reaction plates.
The preparation method of the phenolic acid glycosyl ester is carried out in a reaction microchannel, and a reticular reaction plate bonded with an organic base catalyst is arranged in the reaction microchannel, so that the mass transfer efficiency can be improved, the reaction degree is enhanced by providing a large catalytic activity specific surface in the reaction microchannel, the separation and purification cost of reaction products is greatly reduced, and the preparation method has the advantages of convenience in operation, economy and high efficiency.
Preferably, the mixed solution of the carbohydrate compound and the reaction solvent and the mixed solution of the phenolic acid compound and the reaction solvent flow in the reaction microchannel for 10-40 min.
The invention provides a preparation device of phenolic acid glycosyl ester, which is provided with a reaction micro-channel and a heating mechanism, wherein the reaction micro-channel is a hollow pipeline, the heating mechanism radiates to provide heat for the reaction micro-channel, the reaction micro-channel is provided with a liquid inlet and a liquid outlet, a guide plate is arranged in the reaction micro-channel, the guide plate is arranged along the liquid flow direction of the reaction micro-channel, a plurality of netlike reaction plates distributed and arranged are fixed on the surface of the guide plate and the inner surface of the reaction micro-channel, the netlike reaction plates are obliquely fixed on the surface of the guide plate or the inner surface of the reaction micro-channel, the netlike reaction plates are bonded with organic base catalysts, the bonding is that the organic base catalysts are connected to resin through C-N or C-C bonds, and the resin is attached on the surface of the netlike reaction plates.
According to the preparation device of the phenolic acid-based sugar ester, the reticular reaction plate bonded with the organic base catalyst is arranged in the reaction microchannel, the reaction degree is enhanced by providing a large catalytic activity specific surface in the reaction microchannel, the separation and purification cost of reaction products is greatly reduced, and the preparation device has the advantages of convenience in operation, economy and high efficiency.
Preferably, the plurality of netlike reaction plates are symmetrically distributed about the flow guide plate, the plurality of netlike reaction plates are fixed on the surface of the flow guide plate and the inner surface of the reaction microchannel in a fishbone shape, and the netlike reaction plates fixed on the same surface in the plurality of netlike reaction plates are parallel to each other.
According to the preparation device of the phenolic acid-based sugar ester, the reticular reaction plate bonded with the organic base catalyst is fixed on the surface of the guide plate and the inner surface of the reaction microchannel in a fish bone shape, so that the catalytic activity specific surface is improved, the mass transfer efficiency is improved to a greater extent, and the conversion rate of the phenolic acid-based sugar ester is improved.
Preferably, the heating mechanism is a microwave reactor, an inlet of the reaction micro-channel is communicated with a liquid inlet pump, and an outlet of the reaction micro-channel is communicated with a product collector.
Preferably, the length of the reaction microchannel is 3 to 30m.
Preferably, the cross section of the reaction micro-channel is rectangular, and the dimension of the reaction micro-channel is 12×1.5-18×3.2mm.
The invention has the beneficial effects that: the phenolic acid glycosyl ester has better antibacterial and anti-inflammatory biological activity, high skin permeability and high water solubility compared with the existing glycosyl fatty acid ester. The phenolic acid base sugar ester preparation method utilizes the saccharide compound and the phenolic acid compound to prepare the phenolic acid base sugar ester under the catalysis of the organic base catalyst, so that side reaction can be reduced, conversion rate can be improved, product purity can be improved, the preparation method is carried out in a reaction micro-channel, the mass transfer efficiency can be improved by arranging a netlike reaction plate bonded with the organic base catalyst in the reaction micro-channel, the reaction degree can be enhanced, the separation and purification cost of a reaction product can be greatly reduced, and the preparation method has the advantages of convenience in operation, economy and high efficiency.
Drawings
FIG. 1 is a schematic diagram of the apparatus for producing a phenolic acid-based sugar ester according to the present invention.
FIG. 2 is a partial cross-sectional view of a reaction microchannel of the apparatus for producing a phenolic acid-based sugar ester of the present invention.
The reaction micro-channel is characterized by comprising 1, a liquid inlet pump A,2, a liquid inlet pump B,3, a reaction micro-channel bonded with an organic base catalyst, 31, a guide plate, 32, a net-shaped reaction plate, 4, a product collector, 5 and a microwave heater.
Detailed Description
For a better description of the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to the following specific examples.
Example 1
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
in the preparation device of phenolic acid glycosyl ester of this embodiment, as shown in fig. 1 and fig. 2, the preparation device is provided with a reaction micro-channel 3 and a microwave heater 5, the reaction micro-channel 3 is a hollow pipeline, the microwave heater 5 radiates to provide heat for the reaction micro-channel 3, the reaction micro-channel 3 is provided with a liquid inlet and a liquid outlet, a deflector 31 is arranged in the reaction micro-channel 3, the deflector 31 is arranged along the liquid flow direction of the reaction micro-channel 3, a plurality of netlike reaction plates 32 distributed and arranged are fixed on the surface of the deflector 31 and the inner surface of the reaction micro-channel 3, the netlike reaction plates 32 are obliquely fixed on the surface of the deflector 31 or the inner surface of the reaction micro-channel 3, the netlike reaction plates 32 are bonded with organic base catalysts, the bonding is that the organic base catalysts are connected to resin through C-N or C-C bonds, and the resin is coated on the surface of the netlike reaction plates 32 to form a film;
the plurality of netlike reaction plates 32 are symmetrically distributed about the guide plate 31, the plurality of netlike reaction plates 32 are fixed on the surface of the guide plate 31 and the inner surface of the reaction microchannel 3 in a fishbone shape, and the netlike reaction plates fixed on the same surface in the plurality of netlike reaction plates 32 are parallel to each other;
the inlet of the reaction micro-channel 3 is communicated with a liquid inlet pump A1 and a liquid inlet pump B2, the outlet of the reaction micro-channel 3 is communicated with a product collector 4, the cross section of the reaction micro-channel 3 is rectangular, the size of the reaction micro-channel 3 is 15 multiplied by 2.5mm, and the length of the reaction micro-channel 3 is 15m.
The preparation method of the phenolic acid glycosyl ester of the embodiment is applied to the preparation device, and comprises the following steps:
(1) Glucose is prepared into a glucose solution with the mass concentration of 5% by using N, N-dimethylformamide, and methyl parahydroxybenzoate is prepared into a methyl parahydroxybenzoate solution with the mass concentration of 5%;
(2) Controlling the internal temperature of a reaction microchannel to be 120 ℃ by a microwave heater, and mixing glucose solution and methyl parahydroxybenzoate solution according to the molar ratio of 1:1 respectively inputting the mixed solution into a reaction micro-channel through a liquid inlet pump A1 and a liquid inlet pump B2, mixing to obtain a mixed solution, continuously flowing through the reaction micro-channel for reaction, wherein the flowing time of the mixed solution in the reaction micro-channel is 20min, and collecting a product through a product collector communicated with an outlet of the reaction micro-channel.
And (3) product testing: evaporating the product in the product collector to remove solvent, performing high performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance detection, performing MS-ESI (-) on the main product,m/z：299.0764(M-H) - i.e. the molecular weight of the main product is 300.08; 1 H 13 the C HMBC two-dimensional nuclear magnetic results show a cross-peak of hydrogen with chemical shifts 4.27 and 4.37ppm and carbon with chemical shifts 174.5ppm, indicating that the carbonyl group of methyl parahydroxybenzoate reacts with the hydroxyl group of glucose C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and then subjected to high performance liquid chromatography-evaporative light scattering (HPLC-ELSD) analysis, with a glucose conversion of 98%, a methylparaben conversion of 97% and a yield of 96%.
Example 2
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present embodiment and that of the embodiment 1 is that: the methyl p-hydroxybenzoate was replaced with methyl protocatechuic acid.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 315.0784 (M-H) - I.e. the molecular weight of the main product is 316.08; 1 H 13 the chmbc two-dimensional nuclear magnetic results showed cross peaks of hydrogen with chemical shifts 4.27 and 4.37ppm and carbon with chemical shifts 174.5ppm, indicating that the carbonyl group of the methyl protocatechuic acid reacted with the hydroxyl group of glucose C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 96%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, with a glucose conversion of 98% and a methyl protocatechuic acid conversion of 98% in 97% yield.
Example 3
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present embodiment and that of the embodiment 1 is that: methyl parahydroxybenzoate was replaced with methyl vanillic acid.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 329.0956 (M-H) - I.e. the molecular weight of the main product is 330.10; 1 H 13 the C HMBC two-dimensional nuclear magnetic results show that hydrogen with chemical shifts of 4.27 and 4.37ppm cross peaks with carbon with chemical shifts of 174.5ppm indicating that the carbonyl group of methyl vanillic acid reacts with the hydroxyl group of glucose C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, the glucose conversion was 98%, the methyl vanillic acid conversion was 97% and the yield was 96%.
Example 4
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present embodiment and that of the embodiment 1 is that: methyl parahydroxybenzoate was replaced with methyl sinapite.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 385.1167 (M-H) - I.e. the molecular weight of the main product is 386.12; 1 H 13 c HMBC two-dimensional nuclear magnetism result display and conversionThe chemical shifts 4.27 and 4.37ppm of hydrogen cross peaks with 174.5ppm of carbon indicating that the carbonyl group of methyl sinapite reacted with the hydroxyl group of glucose C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:
the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, with a glucose conversion of 98%, a methyl sinapite conversion of 97% and a yield of 96%.
Example 5
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present embodiment and that of the embodiment 1 is that: glucose was replaced with glucosamine.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 298.0899 (M-H) - I.e. the molecular weight of the main product is 299.10; 1 H 13 the C HMBC two-dimensional nuclear magnetic results show a cross-peak of hydrogen with chemical shifts of 4.27 and 4.37ppm and carbon with chemical shifts of 174.5ppm, indicating that the carbonyl group of methyl parahydroxybenzoate reacts with the hydroxyl group of glucosamine C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, the conversion of glucosamine was 97%, the conversion of methylparaben was 98% and the yield was 95%.
Example 6
As one of the phenolic acid glycosyl esters of the embodiments of the present invention,the phenolic acid glycosyl ester has the following structure:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present example and that of example 5 is that: the methyl parahydroxybenzoate was replaced with methyl gallate.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 330.0854 (M-H) - I.e. the molecular weight of the main product is 331.09; 1 H 13 the two-dimensional nuclear magnetic results of chmbc showed cross peaks of hydrogen with chemical shifts 4.27 and 4.37ppm and carbon with chemical shifts 174.5ppm, indicating that the carbonyl group of methyl gallate reacted with the hydroxyl group of glucosamine C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, the conversion of glucosamine was 97%, the conversion of methyl gallate was 98%, and the yield was 95%.
Example 7
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present example and that of example 5 is that: methyl parahydroxybenzoate was replaced with methyl vanillic acid.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 328.1023 (M-H) - I.e. the molecular weight of the main product is 329.11; 1 H 13 the two-dimensional nuclear magnetic resonance results of the C HMBC show that the hydrogen with chemical shifts of 4.27 and 4.37ppm and the carbon with chemical shift of 174.5ppm show cross peaks, indicating the carbonyl and amino groups of the methyl vanillic acid esterThe hydroxyl groups of glucose C6 react to form esters. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 96%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, the conversion of glucosamine was 98%, the conversion of methyl vanillic acid was 98% and the yield was 96%.
Example 8
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present example and that of example 5 is that: the methyl p-hydroxybenzoate was replaced with methyl ferulate.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 354.1205 (M-H) - I.e. the molecular weight of the main product is 355.13; 1 H 13 the two-dimensional nuclear magnetic results of the chmbc showed cross peaks of hydrogen with chemical shifts 4.27 and 4.37ppm and carbon with chemical shifts 174.5ppm, indicating that the carbonyl group of methyl ferulate reacted with the hydroxyl group of glucosamine C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, with a glucosamine conversion of 98%, a methyl ferulate conversion of 98% and a yield of 95%.
Example 9
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present embodiment and that of the embodiment 1 is that: sucrose was used to replace glucose and methyl protocatechuic acid was used to replace methyl parahydroxybenzoate.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 477.1237 (M-H) - I.e. the molecular weight of the main product is 478.13; 1 H 13 the C HMBC two-dimensional nuclear magnetic results show a cross-peak of hydrogen with chemical shifts 4.27 and 4.37ppm and carbon with chemical shifts 174.5ppm, indicating that the carbonyl group of the methyl protocatechuic acid reacts with the hydroxyl group of sucrose C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, the sucrose conversion was 99%, the protocatechuic acid methyl ester conversion was 98%, and the yield was 95%.
Example 10
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present example and that of example 9 is that: methyl ester of protocatechuic acid is replaced by methyl ester of vanillic acid.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 491.1418 (M-H) - I.e. the molecular weight of the main product is 492.15; 1 H 13 the two-dimensional nuclear magnetic results of chmbc showed cross peaks of hydrogen at chemical shifts 4.27 and 4.37ppm and carbon at chemical shifts 174.5ppm, indicating that the carbonyl group of methyl vanillic acid reacted with the hydroxyl group of sucrose C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:the purity was 95%. />
Reaction evaluation: the product in the collector was evaporated to dryness and subjected to HPLC-ELSD analysis, the sucrose conversion was 99%, the methyl vanillic acid conversion was 98% and the yield was 95%.
Example 11
As an embodiment of the present invention, the structure of the phenolic acid glycosyl ester is as follows:
the only difference between the preparation method of the phenolic acid glycosyl ester of the present example and that of example 9 is that: the methyl ferulate is used for replacing the protocatechuic acid methyl ester.
And (3) product testing: evaporating the product in the collector to dryness, and then carrying out HPLC-MS and nuclear magnetic resonance detection, wherein the MS-ESI (-), m/z of the main product are as follows: 517.1518 (M-H) - I.e. the molecular weight of the main product is 518.16; 1 H 13 the two-dimensional nuclear magnetic results of the C HMBC show that the hydrogen with chemical shifts of 4.27 and 4.37ppm and the carbon with chemical shift of 174.5ppm show cross peaks, which means that the carbonyl of the methyl ferulate reacts with the hydroxyl of sucrose C6 to form an ester. According to mass spectrum and nuclear magnetism result analysis, the chemical structure of the product is as follows:
the purity was 95%.
Reaction evaluation: the product in the collector was evaporated to dryness and then subjected to HPLC-ELSD analysis, with a sucrose conversion of 99%, a methyl ferulate conversion of 99% and a yield of 95%.
Performance test
The antibacterial and anti-inflammatory properties of the phenolic acid glycosyl esters of examples 1-11 were tested.
The antibacterial properties of the phenolic acid glycosyl esters of examples 1 to 11 were evaluated by the shaking method of GB/T20944.3-2008, and gram-positive bacteria, staphylococcus aureus (ATCC 25923) and gram-negative bacteria, escherichia coli (ATCC 25922), were used as test bacteria. Respectively adding test bacteria into nutrient broth culture solution, oscillating at 30deg.C for 24 hr/min for activation to obtain bacterial suspension, testing in two groups, and sequentially adding 0.3mL staphylococcus aureus bacterial suspension, 20mL Phosphate (PBS) buffer solution, and 0.5mg phenolic acid glycosyl ester sample of example 1-example 11 into the first group of 11 test bottles; to a second set of 11 test flasks, 0.3mL of E.coli suspension, 20mL of Phosphate Buffer (PBS), and 1mg of the phenolic acid glycosylester sample of examples 1-11 were added, respectively, in sequence; each group was blank with the test without any test piece added, the test piece was sealed and oscillated at 24℃for 18 hours at 150 r/min. Taking 0.1mL of test solution from each test bottle, diluting by adopting a 10-fold dilution method, taking 0.1mL of test solution, transferring into a nutrient broth agar culture dish, shaking uniformly, placing into an incubator, culturing for 24 hours at 30 ℃, comparing the colony numbers of a blank group and a test group under the optimal dilution condition, and calculating the antibacterial rate, thereby evaluating the antibacterial performance of the phenolic group sugar ester. The results are shown in Table 1:
note that: c (C) Blank space : colony count of blank group; c (C) Experiment : colony count of the experimental group.
Table 1 antibacterial effect of phenolic acid sugar esters on the test bacteria in 2.
| Phenolic acid sugar ester sample | Bacterial strain | Bacteriostasis rate (%) 1 | Bacterial strain | Bacteriostasis rate (%) 2 |
| Example 1 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.91％ |
| Example 2 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.93％ |
| Example 3 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.91％ |
| Example 4 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.91％ |
| Example 5 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.99％ |
| Example 6 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.99％ |
| Example 7 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.99％ |
| Example 8 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.99％ |
| Example 9 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.99％ |
| Example 10 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.99％ |
| Example 11 | Staphylococcus aureus | 99.99％ | Coli bacterium | 99.99％ |
1 Phenolic acid sugar ester sample concentration: 25 μg/mL; 2 phenolic acid sugar ester sample concentration: 50. Mu.g/mL.
As is clear from Table 1, when the concentration of the phenolic acid sugar ester was 25. Mu.g/mL, it was found that it was possible to kill at least 99.99% of Staphylococcus aureus; and when the concentration of the phenolic acid sugar ester is 50 mug/mL, more than 99.9% of escherichia coli can be killed. The phenolic acid glycosyl ester has obvious antibacterial performance. And the phenolic acid-based glucosamine esters of examples 5-8, the phenolic acid-based sucrose esters of examples 9-11 were found to have better antibacterial properties.
The inhibition of lipopolysaccharide-induced inflammatory response of mouse macrophage RAW264.7 was examined by measuring Nitric Oxide (NO) content using the Griess method. After passage of the mouse macrophage RAW264.7 cells, they were cultured in high sugar cell medium DMEM (dulbecco's minimum essential medium, DMEM, gibico) containing 10% Fetal Bovine Serum (FBS), various concentrations of phenolic acid glycosyl ester (10-100. Mu.g/mL) were added, bacterial lipopolysaccharide (1. Mu.g/mL) was used to induce inflammatory reaction, and the supernatant was collected after 16 hours. The Griess method is used for measuring the NO content in cell supernatant, and according to the influence of different concentrations on the release of NO by bacterial lipopolysaccharide-induced RAW264.7 cells, the method is used for reacting the NO level and evaluating the anti-inflammatory performance of phenolic acid-based sugar esters. The results are shown in Table 2:
table 2 inhibitory effect of phenolic acid based sugar esters on bacterial lipopolysaccharide induced release of NO by RAW264.7 cells.
As shown in Table 2, the phenolic acid glycosyl ester can effectively inhibit bacterial lipopolysaccharide-induced mouse macrophage RAW264.7 from generating excessive inflammatory mediator NO, and the effect shows concentration dependence and has excellent anti-inflammatory performance.
Finally, it should be noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the scope of the present invention, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present invention may be modified or substituted equally without departing from the spirit and scope of the technical solution of the present invention.
Claims (5)
1. A phenolic acid glycosyl ester, characterized in that the phenolic acid glycosyl ester has the structure shown below:
2. a process for the preparation of a phenolic acid-based sugar ester according to claim 1, characterized in that the process comprises the steps of: mixing a saccharide compound, a phenolic acid compound and an organic base catalyst, and then reacting in a reaction solvent at 110-140 ℃; the reaction is carried out in a reaction microchannel, a mixed solution of a carbohydrate compound and a reaction solvent, a phenolic acid compound and the reaction solvent flow through the reaction microchannel, the reaction microchannel is a hollow pipeline, the reaction microchannel is provided with a liquid inlet and a liquid outlet, a guide plate is arranged in the reaction microchannel, the guide plate is arranged along the liquid flow direction of the reaction microchannel, a plurality of netlike reaction plates distributed and arranged are fixed on the surface of the guide plate and the inner surface of the reaction microchannel, the netlike reaction plates are obliquely fixed on the surface of the guide plate or the inner surface of the reaction microchannel, an organic base catalyst is bonded on the netlike reaction plates, and the organic base catalyst is connected to resin through C-N or C-C bonds and is attached on the surface of the netlike reaction plates.
3. The method for producing a phenolic acid-based sugar ester according to claim 2, wherein the saccharide compound is glucose, glucosamine or sucrose; the phenolic acid compound is methyl p-hydroxybenzoate, protocatechuic acid methyl ester, gallic acid methyl ester, methyl vanillic acid methyl ester, methyl syringate, 4-hydroxy cinnamic acid methyl ester, caffeic acid methyl ester, 3,4, 5-trihydroxy cinnamic acid methyl ester, ferulic acid methyl ester or sinapic acid methyl ester; the organic base catalyst is 1,5, 7-triazabicyclo [4.4.0] dec-5-ene, 1, 8-diazabicyclo undec-7-ene and 1, 5-diazabicyclo [4.3.0] non-5-ene, and the reaction solvent is dimethyl sulfoxide or N, N-dimethylformamide.
4. The preparation device of the phenolic acid glycosyl sugar ester is characterized in that the preparation device is provided with a reaction micro-channel and a heating mechanism, the reaction micro-channel is a hollow pipeline, the heating mechanism radiates to provide heat for the reaction micro-channel, the reaction micro-channel is provided with a liquid inlet and a liquid outlet, a guide plate is arranged in the reaction micro-channel, the guide plate is arranged along the liquid flow direction of the reaction micro-channel, a plurality of netlike reaction plates distributed and arranged are fixed on the surface of the guide plate and the inner surface of the reaction micro-channel, the netlike reaction plates are obliquely fixed on the surface of the guide plate or the inner surface of the reaction micro-channel, an organic base catalyst is bonded on the netlike reaction plates, and the organic base catalyst is connected to resin through C-N or C-C bonds and is attached to the surface of the netlike reaction plates.
5. The apparatus for preparing phenolic acid-based sugar ester according to claim 4, wherein the plurality of mesh-shaped reaction plates are symmetrically distributed about the baffle, the plurality of mesh-shaped reaction plates are fixed on the surface of the baffle and the inner surface of the reaction microchannel in a fishbone shape, the mesh-shaped reaction plates fixed on the same surface among the plurality of mesh-shaped reaction plates are parallel to each other, the heating mechanism is a microwave reactor, the inlet of the reaction microchannel is communicated with a liquid inlet pump, and the outlet of the reaction microchannel is communicated with a product collector.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110252991.2A CN113072602B (en) | 2021-03-08 | 2021-03-08 | Phenolic acid glycosyl ester and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110252991.2A CN113072602B (en) | 2021-03-08 | 2021-03-08 | Phenolic acid glycosyl ester and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113072602A CN113072602A (en) | 2021-07-06 |
| CN113072602B true CN113072602B (en) | 2023-08-01 |
Family
ID=76612453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110252991.2A Active CN113072602B (en) | 2021-03-08 | 2021-03-08 | Phenolic acid glycosyl ester and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113072602B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118406096B (en) * | 2024-06-28 | 2024-08-23 | 成都施贝康生物医药科技有限公司 | Maltose fatty acid ester compound and preparation method and application thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07179348A (en) * | 1993-12-22 | 1995-07-18 | Tsumura & Co | Cerebral function improver comprising sucrose acryl compound as active ingredient |
| JP3897064B2 (en) * | 1996-02-27 | 2007-03-22 | 株式会社ニチレイ | Method for producing phenolic sugar ester |
| FR2759370B1 (en) * | 1997-02-12 | 2000-08-11 | Oreal | NOVEL SALICYLIC ACID DERIVATIVES AND THEIR USE IN COSMETIC OR DERMATOLOGICAL COMPOSITIONS |
| CN101209254B (en) * | 2006-12-29 | 2011-04-20 | 江苏正大天晴药业股份有限公司 | New use of polyhydroxy galloyl-beta-D-glucose derivatives |
| CN106215828A (en) * | 2016-09-23 | 2016-12-14 | 中国科学院上海高等研究院 | A kind of microchannel reaction unit, microchannel response system and the method preparing alkene |
-
2021
- 2021-03-08 CN CN202110252991.2A patent/CN113072602B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN113072602A (en) | 2021-07-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109750070B (en) | Functional mulberry leaf oligosaccharide and preparation method and application thereof | |
| CN113072602B (en) | Phenolic acid glycosyl ester and preparation method thereof | |
| CN103525717B (en) | Anaerobic alginate decomposing bacterium and application thereof | |
| Ibrahim et al. | Antibacterial activity of vanillic acid and catechol produced by microbial biotransformation of caffiec acid | |
| CN116356561A (en) | Copper-based MOF nanofiber membrane and preparation method and application thereof | |
| Ogasawara et al. | Identification of actinomycin D as a specific inhibitor of the alternative pathway of peptidoglycan biosynthesis | |
| WO2018155485A1 (en) | Novel microorganism and production method for urolithins using same | |
| JP5667976B2 (en) | Production method of organic acids | |
| JP2011153096A (en) | Fluorescent sugar-chain probe | |
| CN103131649B (en) | Pseudomonas fluorescens and application in preparation of transform-4-aminomethyl-naphthenic acid thereof | |
| CN109136285A (en) | A kind of catechin bioconversion nutrient solution and a kind of method for promoting catechin bioconversion | |
| Kawsar et al. | Infrared, 1H-NMR spectral studies of some methyl 6-O-myristoyl-α-D-glucopyranoside derivatives: assessment of antimicrobial effects | |
| CN113072534B (en) | RNA fluorescent probe and preparation method and application thereof | |
| CN104945636B (en) | A kind of composite, Its Preparation Method And Use | |
| CA3038021A1 (en) | Compound or salt thereof, anti-inflammatory agent, anti-cancer agent against lung cancer, method of producing compound or salts thereof, method of treating inflammatory diseases and method of treating lung cancer | |
| Zhang et al. | Enzymatic synthesis of naringin palmitate | |
| CN109810157B (en) | Synthesis method of beta-glucuronidase precipitation type fluorogenic substrate | |
| Hoidy et al. | Synthesis, characterization and evaluation of biological activity of corn oil-based difatty acyl carbamodithioic acid | |
| CN109651326B (en) | Fluorescent probe for covalently connecting labeled cells and method for tracking labeled cells | |
| Thaeder et al. | Chemo-Enzymatic Synthesis and Biological Assessment of p-Coumarate Fatty Esters: New Antifungal Agents for Potential Plant Protection | |
| CN103497200A (en) | Dihydroartemisinin higher fatty acid ester and preparation method thereof | |
| CN114874171B (en) | Aloesin and preparation method and application thereof | |
| CN114933618A (en) | Rhamnolipid derivative and preparation method and application thereof | |
| Lou et al. | Regioselective synthesis of α-d-glucopyranosiduronic acid derivatives and biological test against bacterial Staphylococcus aureus and Salmonella agona | |
| Camargo et al. | Radiometric measurement of differential metabolism of fatty acids by Mycobacterium lepraemurium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |