CN107098924A - A kind of amino acid derivativges of aryl-boric acid ester modification and preparation method and application - Google Patents
A kind of amino acid derivativges of aryl-boric acid ester modification and preparation method and application Download PDFInfo
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- CN107098924A CN107098924A CN201710355497.2A CN201710355497A CN107098924A CN 107098924 A CN107098924 A CN 107098924A CN 201710355497 A CN201710355497 A CN 201710355497A CN 107098924 A CN107098924 A CN 107098924A
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- amino acid
- boric acid
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- acid ester
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- 239000004327 boric acid Substances 0.000 title claims abstract description 44
- 150000001413 amino acids Chemical class 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 230000004048 modification Effects 0.000 title claims abstract description 17
- 238000002715 modification method Methods 0.000 title abstract description 3
- 230000004044 response Effects 0.000 claims abstract description 20
- 150000003862 amino acid derivatives Chemical class 0.000 claims abstract description 7
- -1 methylene, ethylidene Chemical group 0.000 claims description 16
- 238000012986 modification Methods 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 5
- CYMXTKNOROVINH-UHFFFAOYSA-N OC(C)(C)C(C)(C)O.C1(=CC=CC=C1)OB(O)O Chemical compound OC(C)(C)C(C)(C)O.C1(=CC=CC=C1)OB(O)O CYMXTKNOROVINH-UHFFFAOYSA-N 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 3
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 238000004809 thin layer chromatography Methods 0.000 claims description 3
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical compound ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000003519 biomedical and dental material Substances 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- 150000004702 methyl esters Chemical class 0.000 claims description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 2
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 claims description 2
- 239000012429 reaction media Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- XWNCPKWKHYVDEW-UHFFFAOYSA-N B(O)(O)OC(C)(C)C(C)(C)O.C(C1=CC=CC=C1)Br Chemical group B(O)(O)OC(C)(C)C(C)(C)O.C(C1=CC=CC=C1)Br XWNCPKWKHYVDEW-UHFFFAOYSA-N 0.000 claims 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 230000003647 oxidation Effects 0.000 abstract description 14
- 238000007254 oxidation reaction Methods 0.000 abstract description 14
- 239000000463 material Substances 0.000 abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 4
- 238000009833 condensation Methods 0.000 abstract description 3
- 230000005494 condensation Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 230000009257 reactivity Effects 0.000 abstract description 3
- 239000011149 active material Substances 0.000 abstract description 2
- 239000013543 active substance Substances 0.000 abstract description 2
- 238000010276 construction Methods 0.000 abstract description 2
- 230000000717 retained effect Effects 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 18
- 235000004400 serine Nutrition 0.000 description 9
- JJIHLJJYMXLCOY-BYPYZUCNSA-N N-acetyl-L-serine Chemical compound CC(=O)N[C@@H](CO)C(O)=O JJIHLJJYMXLCOY-BYPYZUCNSA-N 0.000 description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000003355 serines Chemical class 0.000 description 3
- 235000008521 threonine Nutrition 0.000 description 3
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 2
- SVENKGKXRLHCTC-UHFFFAOYSA-N B(O)(O)O.BrCC=1C=CC=CC1 Chemical class B(O)(O)O.BrCC=1C=CC=CC1 SVENKGKXRLHCTC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KWGACYZYFZTYRN-UHFFFAOYSA-N OC(C)(C)C(C)(C)O.B(O)(O)O.BrCC1=CC=CC=C1 Chemical class OC(C)(C)C(C)(C)O.B(O)(O)O.BrCC1=CC=CC=C1 KWGACYZYFZTYRN-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000012867 bioactive agent Substances 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 235000010338 boric acid Nutrition 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 0 CC1(C)OB(c2ccc(CO*C*)cc2)OC1(C)C Chemical compound CC1(C)OB(c2ccc(CO*C*)cc2)OC1(C)C 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- WITZXUPUMRPBJS-UHFFFAOYSA-N [B].BrCC1=CC=CC=C1 Chemical compound [B].BrCC1=CC=CC=C1 WITZXUPUMRPBJS-UHFFFAOYSA-N 0.000 description 1
- LXDRHVXMGDKBEK-UHFFFAOYSA-N [B].C1=CC=CC=C1 Chemical compound [B].C1=CC=CC=C1 LXDRHVXMGDKBEK-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000011506 response to oxidative stress Effects 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses amino acid derivativges of a kind of aryl-boric acid ester modification and preparation method and application, the structure of the derivative is shown in formula I.The preparation method of amino acid derivativges of the present invention is simple, obtained aryl-boric acid ester modified amino acid derivative is on the basis of the reactivity of its amino and/or carboxyl is retained, introduce oxidation response, there is provided a kind of construction unit of new oxidation response material, using ripe amino acid modified and condensation technology, structure and the performance regulation and control of oxidation response active agent and material are conveniently realized, are widely used in intelligent response type biomedical materials field.
Description
Technical field
The invention belongs to technical field of biological material, the amino acid derivativges and its system of more particularly to a kind of aryl-boric acid ester modification
Preparation Method and application.
Background technology
Amino acid is the organic matter that a class has amino and carboxyl, is that the substantially single of protein molecule is constituted in organism
Position, the vital movement with biology is closely related, therefore amino acid and its biologically active polypeptide and protein of condensation composition are in doctor
There is important application value in treatment field.
In recent years, polymer-amino-acid, including polyaminoacid, false amino acid and amino acid-non-amino acid copolymer
Due to good biocompatibility and degradability, and regulatable physics, chemistry and biology performance etc., in base
The application of the bio-medical fields such as cause/medicament carrier system and organizational project and artificial organs is received significant attention.
Experience environmental stimuli using amino acid and its derivative and produce some physically or chemically significant changes responses
Property, macromolecule can be introduced as sensing unit and builds stimulating responsive functional high molecule material, such as available histidine
Acid-base value sensitive polymer micella is built, realizes that the endosome of medicine and gene is escaped.
Aryl-boric acid ester is a kind of important organic synthesis intermediate and medicine, agricultural chemicals, chemical intermediate, because it has
Hypotoxicity and environment amenable boric acid is finally degraded into, in recent years in bioactive agents or bio-medical material are prepared
Play a significant role, such as the H of aryl-boric acid ester2O2Oxidative degradation is used to build oxidative stress response release system.
But the preparation of existing aryl-boric acid ester oxidation Response System and combination property also have lifting to be optimized, can not still meet
Actual application needs.
The content of the invention
The primary and foremost purpose of the present invention is to overcome what the shortcoming and deficiency of prior art were modified there is provided a kind of aryl-boric acid ester
Amino acid derivativges, on the hydroxyl of hydroxy-amino-acid and its derivative introduce phenyl boric acid pinacol ester, retain amino acid and
On the basis of the reactivity of its derivative amino and/or carboxyl, oxidation response is introduced, its function is expanded.
Another object of the present invention is to provide the preparation method of the aryl-boric acid ester modified amino acid derivative, obtain
A kind of structure primitive of bioactive agents and biomaterial with oxidation sensitive.
It is still another object of the present invention to provide the application of the aryl-boric acid ester modified amino acid derivative.
The purpose of the present invention is achieved through the following technical solutions：
A kind of amino acid derivativges of aryl-boric acid ester modification, with structure shown in formula I：
Wherein：R is methylene, ethylidene or phenylene；
R1For H, formoxyl, acetyl group, phthalyl, tertiary butyl oxycarbonyl (Boc), tablet held before the breast by officials methoxycarbonyl group (Fmoc) or
Benzyl；
R2For H, methyl esters or ethyl ester.
The preparation method of the amino acid derivativges of above-mentioned aryl-boric acid ester modification, comprises the following steps：
Hydroxyl amino acid derivative is dissolved in anhydrous response medium and obtains solution A；Alkali, benzene boron are added in solution A successively
6~24h is reacted under sour pinacol ester, anhydrous condition, thin-layer chromatography (TLC) detects that its reaction is complete；By obtained aryl boric acid
Ester modified amino acid derivative crude product obtains aryl-boric acid ester modified amino acid sterling through isolating and purifying；
The mol ratio preferably 1.1 of described hydroxyl amino acid derivative, phenyl boric acid pinacol ester and alkali:1.0:3.0.
Described hydroxyl amino acid derivative has the structure as shown in Formula II：
The preferred dimethyl sulfoxide (DMSO) of described reaction medium, N,N-dimethylformamide or carbon dichloride.
Described alkali is organic base or inorganic base；
The preferred N of described organic base, N- diisopropylethylamine or triethylamine.
The preferred K of described inorganic base2CO3、Na2CO3, NaOH, KOH, NaH or KH.
The preferred 4- bromomethyl benzene boric acids pinacol ester of described phenyl boric acid pinacol ester.
Preferably 12~24h of described reaction time.
Described isolating and purifying preferably disperses, extracts, is spin-dried for and chromatographed.
By taking acetyl serine as an example, the reaction equation of aryl-boric acid ester modified amino acid derivative is prepared using the inventive method
And oxidation response principle is as follows：
Prepare the reaction equation that aryl-boric acid ester modifies acetyl serine
Aryl-boric acid ester modifies the oxidation response principle of acetyl serine
The amino acid derivativges of above-mentioned aryl-boric acid ester modification can be applied in intelligent response biomedical materials field,
It is particularly suitable for preparing intelligent response type implant, medicine/gene carrier and biological detection material or apparatus etc..
The present invention has the following advantages and effect relative to prior art：
The preparation method of amino acid derivativges of the present invention is simple, and obtained aryl-boric acid ester modified amino acid derivative is being protected
On the basis of the reactivity for staying its amino and/or carboxyl, introducing oxidation response, there is provided a kind of new oxidation response material
Construction unit, using ripe amino acid modified and condensation technology, conveniently realize oxidation response active agent and material
Structure and the performance regulation and control of material, are widely used in intelligent response type biomedical materials field.
Brief description of the drawings
Fig. 1 is aryl-boric acid ester modification Boc serines1H NMR spectras.
Fig. 2 is the mass spectrogram that aryl-boric acid ester modifies Boc serines.
Fig. 3 is aryl-boric acid ester modification acetyl serine1HNMR spectrograms.
Fig. 4 is the mass spectrogram that aryl-boric acid ester modifies acetyl serine.
Fig. 5 is H2O2Aryl-boric acid ester is handled to modify after Boc serines1H NMR spectras.
Embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited
In this.
Embodiment 1
Aryl-boric acid ester modifies the preparation of tertbutyloxycarbonyl serine, comprises the following steps：
677mg (3.3mmol) tertbutyloxycarbonyl (Boc) serine (C8H15NO5) 20mL dry DMF is dissolved in, add
216mg (9mmol) NaH, stirs 30min, adds the 20mL containing 890mg (3mmol) 4- bromomethyl benzene boric acid pinacol esters
Dry DMF, reacts at room temperature 12h.Reaction finishes water-dispersible, each three times of chloroform, ethyl acetate extraction system, collects organic
Phase, is spin-dried for, and column chromatography obtains aryl-boric acid ester modification tertbutyloxycarbonyl serine 700mg, its1H NMR spectras and molecular formula are such as
Shown in Fig. 1, mass spectrogram is shown in Fig. 2.
Embodiment 2
Aryl-boric acid ester modifies the preparation of tertbutyloxycarbonyl serine methylester, comprises the following steps：
756mg (3.3mmol) tertbutyloxycarbonyl (Boc) serine methylester (C9H17NO5) molten with 20mL anhydrous acetonitrile
Solve, add 486mg (9mmol) potassium hydroxide, stir 30min, where is addition 890mg (3mmol) 4- bromomethyl benzene boric acids frequency
Alcohol ester, 65 DEG C of reaction 2h, suction filtration, filtrate is spin-dried for, and column chromatography purifying obtains aryl-boric acid ester modification tertbutyloxycarbonyl serine first
Ester.
Embodiment 3
Aryl-boric acid ester modifies the preparation of acetyl serine, comprises the following steps：
485mg (3.3mmol) acetyl serine 8mL dry DMF dissolves, plus 216mg (9mmol) NaH, ice bath
Under the conditions of stir 30min, after taking 890mg (3mmol) 4- bromomethyl benzene boric acids ester to finish, moisture dissipate, be extracted with ethyl acetate
Three times, collect organic phase, anhydrous Na2SO4It is dried overnight, is spin-dried for, column chromatography purifying obtains aryl-boric acid ester modification acetyl silk ammonia
Acid, its1H NMR spectras are as shown in figure 3, mass spectrogram is shown in Fig. 4.
Embodiment 4
Aryl-boric acid ester modifies the preparation of tablet held before the breast by officials methoxycarbonyl group tyrosine, comprises the following steps：
1.33g (3.3mmol) tablet held before the breast by officials methoxycarbonyl group (Fmoc) tyrosine (C24H21NO5) with 8mL CH2Cl2Dissolving, plus
1.44mL (9mmol) DIPEA, stirs 30min, adds 2mL bromomethyl benzene boron containing 890mg (3mmol) 4-
The CH of sour pinacol ester2Cl2Solution, reacts at room temperature 24h.It is spin-dried for, column chromatography purifying obtains aryl-boric acid ester modification Fmoc junket ammonia
Acid.
Embodiment 5
Aryl-boric acid ester modifies the preparation of tablet held before the breast by officials methoxycarbonyl group threonine, comprises the following steps：
1.13g (3.3mmol) tablet held before the breast by officials methoxycarbonyl group (Fmoc) threonine (C19H19NO5) with 8mL CH2Cl2Dissolving, is added
1.25mL (9mmol) triethylamine, stirs 30min, adds 2mL and contains 890mg (3mmol) 4- bromomethyl benzene boric acid pinacol esters
CH2Cl2, react at room temperature 16h.It is spin-dried for, column chromatography purifying obtains aryl-boric acid ester modification Fmoc threonines.
Embodiment 6
Aryl-boric acid ester modifies the oxidation response of tertbutyloxycarbonyl serine
Aryl-boric acid ester modification tertbutyloxycarbonyl serine prepared by embodiment 1 is dissolved in H containing 50mM2O2D2O2/
In DMSO-d6 solution, 3 days are incubated at 37 DEG C, it is tested1H NMR spectras are as shown in figure 5, aryl-boric acid ester modifies tertiary butyloxycarbonyl
Oxidation Decomposition occurs for base serine, it was demonstrated that it has oxidation response.
Above-described embodiment is preferably embodiment, but embodiments of the present invention are not by above-described embodiment of the invention
Limitation, other any Spirit Essences without departing from the present invention and the change made under principle, modification, replacement, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (8)
1. a kind of amino acid derivativges of aryl-boric acid ester modification, it is characterised in that with structure shown in formula I：
Wherein：R is methylene, ethylidene or phenylene；
R1For H, formoxyl, acetyl group, phthalyl, tertiary butyl oxycarbonyl, tablet held before the breast by officials methoxycarbonyl group or benzyl；
R2For H, methyl esters or ethyl ester.
2. the preparation method for the amino acid derivativges that aryl-boric acid ester described in claim 1 is modified, it is characterised in that including following
Step：
Hydroxyl amino acid derivative is dissolved in anhydrous response medium and obtains solution A；Alkali, phenyl boric acid frequency are added in solution A successively
6~24h is reacted under any alcohol ester, anhydrous condition, thin-layer chromatography detects that its reaction is complete；Obtained aryl-boric acid ester is modified into amino
Acid derivative crude product obtains aryl-boric acid ester modified amino acid sterling through isolating and purifying；
Described hydroxyl amino acid derivative has the structure as shown in Formula II：
The mol ratio of described hydroxyl amino acid derivative, phenyl boric acid pinacol ester and alkali is 1.1:1.0:3.0.
3. preparation method according to claim 2, it is characterised in that：Described reaction medium is dimethyl sulfoxide (DMSO), N, N-
Dimethylformamide or carbon dichloride.
4. preparation method according to claim 2, it is characterised in that：Described alkali is organic base or inorganic base.
5. preparation method according to claim 4, it is characterised in that：Described organic base be N, N- diisopropylethylamine or
Triethylamine.
6. preparation method according to claim 4, it is characterised in that：Described inorganic base is K2CO3、Na2CO3、NaOH、
KOH, NaH or KH.
7. preparation method according to claim 2, it is characterised in that：Described phenyl boric acid pinacol ester is 4- bromomethyl benzene
Pinacol borate.
8. the amino acid derivativges that aryl-boric acid ester described in claim 1 is modified answering in intelligent response bio-medical material
With.
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| CN201710355497.2A CN107098924A (en) | 2017-05-19 | 2017-05-19 | A kind of amino acid derivativges of aryl-boric acid ester modification and preparation method and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108164700A (en) * | 2017-12-27 | 2018-06-15 | 暨南大学 | It is a kind of to be used to convey active oxygen responsive nano carrier of hydrophobic drug and preparation method thereof |
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| WO2008053185A1 (en) * | 2006-11-01 | 2008-05-08 | Chroma Therapeutics Ltd. | INHIBITORS OF IKK-β SERINE-THREONINE PROTEIN KINASE |
| WO2009027707A2 (en) * | 2007-08-31 | 2009-03-05 | University Of Kent | Methods for preparing peptides, especially radio-labelled peptides |
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| WO2008053185A1 (en) * | 2006-11-01 | 2008-05-08 | Chroma Therapeutics Ltd. | INHIBITORS OF IKK-β SERINE-THREONINE PROTEIN KINASE |
| WO2009027707A2 (en) * | 2007-08-31 | 2009-03-05 | University Of Kent | Methods for preparing peptides, especially radio-labelled peptides |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108164700A (en) * | 2017-12-27 | 2018-06-15 | 暨南大学 | It is a kind of to be used to convey active oxygen responsive nano carrier of hydrophobic drug and preparation method thereof |
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