CN106146614A - A kind of preparation method of RGD tripeptides - Google Patents
A kind of preparation method of RGD tripeptides Download PDFInfo
- Publication number
- CN106146614A CN106146614A CN201510243396.7A CN201510243396A CN106146614A CN 106146614 A CN106146614 A CN 106146614A CN 201510243396 A CN201510243396 A CN 201510243396A CN 106146614 A CN106146614 A CN 106146614A
- Authority
- CN
- China
- Prior art keywords
- aspartic acid
- benzyl ester
- boc
- preparation
- hours
- 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.)
- Pending
Links
- 0 *C(CCCNC(N[N+]([O-])=O)=N)C(NCC(NC(CC(OCc1ccccc1)=O)C(OCc1ccccc1)=O)=O)=O Chemical compound *C(CCCNC(N[N+]([O-])=O)=N)C(NCC(NC(CC(OCc1ccccc1)=O)C(OCc1ccccc1)=O)=O)=O 0.000 description 2
- BIPASOHIPQQHLY-UHFFFAOYSA-N CC(C)(C)OC(NC(CCCNC(N[N+]([O-])=O)=N)C(NCC(NC(CC(OCc1ccccc1)=O)C(OCc1ccccc1)=O)=O)=O)=O Chemical compound CC(C)(C)OC(NC(CCCNC(N[N+]([O-])=O)=N)C(NCC(NC(CC(OCc1ccccc1)=O)C(OCc1ccccc1)=O)=O)=O)=O BIPASOHIPQQHLY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The present invention relates to the preparation method of a kind of RGD tripeptides.The present invention uses liquid phase synthesizing method to synthesize RGD tripeptides, by the selection of reaction condition and optimize can high yield, the highly purified target compound that obtains, target compound RGD purity >=99%.
Description
Technical field
The present invention relates to the preparation method of a kind of RGD tripeptides.
Background technology
RGD peptide is the small peptide that a class contains arginine-glycine-aspartic acid (Arg-Gly-ASP) sequence, is widely present in organism, is the recognition site of integrin (Integrin) and the interaction of its ligandin.Since RGD sequence contained in Pierschbacher was equal to reported first Fibrinogen in 1984 is cell recognition site, RGD peptide and derivant thereof just become the focus of numerous focus of attention and research.In human body, the modal stromatin containing RGD sequence mainly has fiber laminins, (the Temming K such as Collagen type Ⅳ, glass laminins, collagen, thrombostondin, Schiffelers R.M, Molema G, et al.Kok RJ.RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumor vasculature [J] .Drug Resist Updat, 2005,8 (6): 381-402).
Cell adhesion is in the evolution pivotal role in mid-term of cell adhesion disease (cancerometastasis, thrombosis, chemistry cause scorching and osteoporosis).Modulability glycoprotein such as RGD peptide and integrin receptor have the strongest binding ability, may participate in cell adhesion process.Such as RGD peptide is combined with the GP IIb/IIIa receptor-specific of platelet, tumor cell and bone primary surface can intervene thrombosis, cancerometastasis and osteoporotic evolution.This effect of RGD peptide imparts the compound one critical nature containing RGD sequence, the i.e. compound containing RGD sequence and can be enriched with to thrombosis, cancerometastasis and osteoporotic disease sites.Being with a wide range of applications just because of RGD, so one of having become as the biologically active peptide of great researching value, and synthesizing RGD efficiently, efficiently is that its further investigation provides solid foundation.
The synthetic method of RGD mainly has Enzyme catalyzed synthesis method and chemical synthesis at present.In Enzyme catalyzed synthesis method, dicyandiamide solution, water content, temperature, pH, response time and substrate mol ratio etc. all can produce impact to enzymatic activity, and therefore the method reaction condition requires relatively stricter, wayward.Chemical synthesis can be divided into solid phase method and liquid phase method.Up to the present, various solid phase synthesis technique makes people can synthesize various peptide and derivant, but owing to its agents useful for same and cost of equipment are higher, solid phase synthesis is limited to the scale (Huang Weide within 10 grams the most to a great extent, Chen Changqing, " Peptide systhesis ", Science Press, the first edition, 1985).And liquid phase synthesis rule is suitable to synthesize relatively short peptide on a large scale and realize the condensation of fragments of peptides, but the RGD tripeptides purity obtained by current liquid-phase synthesis process is relatively low, about about 80%, and containing residual solvent (such as glacial acetic acid etc.).It is an object of the invention to, by the synthesising process research to RGD tripeptides, overcome the defect of prior art, fast and efficiently synthesis of high purity RGD tripeptides.
Summary of the invention
Concrete route is as follows:
(1) with glycine as initiation material, under the effect of alkali, protect through tertbutyloxycarbonyl (Boc), obtain Boc-glycine (intermediate 1).
(2) Boc-glycine benzyl ester tosilate (raw material 2) double with aspartic acid is condensed under the effect of condensing agent dicyclohexylcarbodiimide (DCC)/DMAP (DMAP) and organic base, obtains the double benzyl ester (intermediate 3) of Boc-glycyl aspartic acid.
(3) the double benzyl ester (intermediate 3) of Boc-glycyl aspartic acid sloughs Boc under trifluoracetic acid (TFA) acts on, and obtains the double benzyl ester trifluoroacetate (intermediate 4) of glycyl aspartic acid.
(4) the double benzyl ester trifluoroacetate of glycyl aspartic acid and N-Boc-N'-NO2-L-arginine (raw material 5) is condensed to yield the double benzyl ester (intermediate 6) of arginyl glycyl aspartic acid under the effect of condensing agent dicyclohexylcarbodiimide DCC/4-dimethylamino naphthyridine DMAP and organic base.
(5) the double benzyl ester (intermediate 6) of arginyl glycyl aspartic acid is taken off Boc under TFA effect and is obtained arginyl glycyl aspartic acid pair benzyl ester trifluoroacetate (intermediate 10).
(6) take off all protection groups through catalytic hydrogenation under arginyl glycyl aspartic acid double benzyl ester trifluoroacetate room temperature, normal pressure and obtain arginyl glycyl aspartic acid tripeptides (RGD).
Step 1 reaction temperature is-5～40 DEG C, preferably 0～30 DEG C；Response time is 12～48 hours, preferably 24 hours；Solvent for use is water, organic solvent or a combination thereof, and organic solvent can be selected for oxolane, dioxane etc., preferably water.
Alkali in step 1 can enumerate sodium hydroxide, potassium hydroxide, Lithium hydrate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, triethylamine, diethylisopropylamide, N-methylmorpholine etc., preferably sodium hydroxide and potassium hydroxide；Glycine and Boc2O mol ratio is 1:1～2, preferably 1:1.5.
Step 2 reaction temperature is 0～30 DEG C, and the response time is 4～12 hours, preferably 6～8 hours；Solvent can enumerate dichloromethane, chloroform etc.；Organic base can enumerate N-methylmorpholine (NMM), triethylamine, diisopropylethylamine etc., the double benzyl ester tosilate of aspartic acid: Boc-glycine: DCC:DMAP: organic base mol ratio is 1:1～3:1～2:0.5～1.5:1～3, preferably 1:1.2～2.5:1～1.5:0.5～1:1.5～2.Under the conditions of Gai, the double benzyl ester (intermediate 3) of Boc-glycyl aspartic acid, and product purity >=99% can be obtained close to quantitative yield.
Step 3 reaction temperature is room temperature, and the response time is 0.5～4 hour, the preferred dichloromethane of solvent, dichloromethane: trifluoracetic acid volume ratio is 1:0.3～1.5, preferably 1:1.Can remove Boc protection group quickly, completely by the method, reaction yield can reach 100%.
Step 4 reaction temperature is 0～30 DEG C, and the response time is 6～24 hours, preferably 10～14 hours；Solvent can enumerate dichloromethane, chloroform etc.；Organic base can enumerate N-methylmorpholine, triethylamine, diisopropylethylamine etc.；N-Boc-N'-NO2-L-arginine: the double benzyl ester trifluoroacetate of glycyl aspartic acid: DCC:DMAP:NMM mol ratio is 1:1～3:1～2:0.5～1.5:1～3, preferably 1:1.2～2.5:1～1.5:0.5～1:1.5～2.
Step 5 reaction temperature is room temperature, and the response time is 2～4 hours, the preferred dichloromethane of solvent, dichloromethane: trifluoracetic acid volume ratio is 1:0.3～1.5, preferably 1:1.
Step 6 reaction temperature is room temperature, and the response time is 6～24 hours, and Pd/C consumption is the 5～30% of double benzyl ester trifluoroacetate (intermediate 10) quality of arginyl glycyl aspartic acid, preferably 10%；Solvent can enumerate water, methanol, ethanol, oxolane, glacial acetic acid, formic acid, dimethyl sulfoxide, dimethylformamide etc., preferably water, methanol, ethanol and oxolane.Reaction yield up to more than 90%, purity >=99%.
Condensing agent in step 2 and step 4 can also select 1-ethyl-3-(3-dimethylamine propyl) carbodiimide hydrochloride EDCI/1-hydroxybenzotriazole HOBt.
Step 3 and step 5 can also be with saturated hydrochloric acid tetrahydrofuran solution, saturated hydrochloric acid dioxane solution or saturated salt acid ethyl acetate solution removal Boc.
Detailed description of the invention
The present invention is illustrated in greater detail below in conjunction with embodiment, but any restriction that the present invention is not recorded by these
The preparation of embodiment 1 Boc-glycine (intermediate 1)
Take glycine (100g, 1.3mol) and be dissolved in 2000mL water, add NaOH (80g, 2mol) under ice bath, under stirring, add Boc2O (350g, 1.6mol), naturally reaction 24 hours it is warmed to room temperature, terminating reaction, reactant liquor ether extracts 2 times, and water layer 1M hydrochloric acid is acidified to pH3～4, ethyl acetate extracts, being evaporated ethyl acetate, residue with Ethyl acetate/petroleum ether recrystallization obtains white solid 215.2g, yield 92%.
The preparation of the double benzyl ester (intermediate 3) of embodiment 2 Boc-glycyl aspartic acid
Take Boc-glycine (42g, 240mmol) it is dissolved in dichloromethane (600mL), DCC (49.5g it is sequentially added under ice bath, 240mmol) DMAP (24.4g, 200mmol), NMM (33ml, 300mmol), double benzyl ester tosilate (the raw material 2) (97g of aspartic acid, 200mmol), room temperature reaction in 5 hours is complete, solvent evaporated, residue with Ethyl acetate solvent, respectively with water, 5%HCl solution, 5%NaHCO3Solution, saturated nacl aqueous solution washs, and organic layer anhydrous sodium sulfate is dried, and filters, solvent evaporated, residue column chromatography purification, obtains grease 93.2g, yield 99%, purity 99.9%.
The preparation of the double benzyl ester trifluoroacetate (intermediate 4) of embodiment 3 glycyl aspartic acid
Take double benzyl ester (the intermediate 3) (47g of Boc-glycyl aspartic acid, 100mmol) it is dissolved in dichloromethane (100mL), trifluoracetic acid (TFA) (100mL) is dripped under stirring, room temperature reaction 1 hour, terminate reaction, solvent evaporated, recrystallization from ethyl acetate/petroleum ether, obtain white solid 45.1g, yield 96%.
The preparation of the double benzyl ester (intermediate 6) of embodiment 4 arginyl glycyl aspartic acid
Take N-Boc-N'-NO2-L-arginine (raw material 5) (38g, 120mmol) it is dissolved in dichloromethane (300mL), DCC (24.8g it is sequentially added under ice bath, 120mmol), DMAP (14.7g, 120mmol), NMM (20mL, 180mmol), the double benzyl ester trifluoroacetate (intermediate 4) (67.5g, 140mmol) of glycyl aspartic acid, room temperature reaction 12 hours, solvent evaporated, residue with Ethyl acetate solvent, respectively with water, 5%HCl solution, 5%NaHCO3Solution, saturated nacl aqueous solution washs, and organic layer anhydrous sodium sulfate is dried, and filters, solvent evaporated, residue column chromatography purification, obtains light yellow solid 75.4g, yield 93%.
The preparation of the double benzyl ester trifluoroacetate (intermediate 10) of embodiment 5 arginyl glycyl aspartic acid
Double benzyl ester (the intermediate 6) (75g of arginyl glycyl aspartic acid, 110mmol) it is dissolved in dichloromethane (150mL), trifluoracetic acid (150mL) is dripped under stirring, room temperature reaction 2 hours, solvent evaporated, recrystallization from ethyl acetate/petroleum ether, obtains white solid 70g, yield 95%.
The preparation of embodiment 6 arginyl glycyl aspartic acid tripeptides (RGD)
Take the double benzyl ester trifluoroacetate (intermediate 10) (20g, 30mmol) of arginyl glycyl aspartic acid and be dissolved in methanol (100mL), add Pd/C (2g), concentrated hydrochloric acid HCl (0.5mL), H2Displacement gas, under room temperature, logical hydrogen reacts 20 hours, terminates reaction, filters Pd/C, solvent evaporated, the white solid 9.8g of water/recrystallizing methanol, yield 94%, purity 99.8%.
The preparation of the double benzyl ester (intermediate 3) of embodiment 7 Boc-glycyl aspartic acid
Take Boc-glycine (17.5g, 100mmol) it is dissolved in dichloromethane (250mL), EDCI (23g it is sequentially added under ice bath, 120mmol) HOBt (20.3g, 150mmol), NMM (38.7ml, 350mmol), double benzyl ester tosilate (the raw material 2) (43.7g of aspartic acid, 90mmol), room temperature reaction in 8 hours is complete, solvent evaporated, residue with Ethyl acetate solvent, respectively with water, 5%HCl solution, 5%NaHCO3Solution, saturated nacl aqueous solution washs, and organic layer anhydrous sodium sulfate is dried, and filters, solvent evaporated, residue column chromatography purification, obtains grease 41.1g, yield 97%, purity 99.4%.
The preparation of the double benzyl ester (intermediate 6) of embodiment 8 arginyl glycyl aspartic acid
Take N-Boc-N'-NO2-L-arginine (raw material 5) (38g, 120mmol) it is dissolved in dichloromethane (300mL), EDCI (27.6g it is sequentially added under ice bath, 144mmol) HOBt (24.3g, 180mmol), NMM (39.8mL, 360mmol), double benzyl ester trifluoroacetate (the intermediate 4) (67.5g of glycyl aspartic acid, 140mmol), room temperature reaction 12 hours, solvent evaporated, residue with Ethyl acetate solvent, respectively with water, 5%HCl solution, 5%NaHCO3Solution, saturated nacl aqueous solution washs, and organic layer anhydrous sodium sulfate is dried, and filters, solvent evaporated, residue column chromatography purification, obtains light yellow solid 72.5g, yield 90%.
The preparation of the double benzyl ester hydrochlorate (intermediate 11) of embodiment 9 glycyl aspartic acid
Take double benzyl ester (the intermediate 3) (47g of Boc-glycyl aspartic acid, 100mmol) it is dissolved in saturated salt acid ethyl acetate solution (200mL), room temperature reaction 2 hours, terminate reaction, solvent evaporated, recrystallization from ethyl acetate/petroleum ether, obtains white solid 37.4g, yield 92%.
The preparation of the double benzyl ester hydrochlorate (intermediate 12) of embodiment 10 arginyl glycyl aspartic acid
The double benzyl ester (intermediate 6) (68g, 100mmol) of arginyl glycyl aspartic acid is dissolved in saturated salt acid ethyl acetate solution (300mL), and 30 DEG C are reacted 2.5 hours, solvent evaporated, recrystallization from ethyl acetate/petroleum ether, obtains white solid 53.6g, yield 88%.
The preparation of the double benzyl ester (intermediate 6) of embodiment 12 arginyl glycyl aspartic acid
Take N-Boc-N'-NO2-L-arginine (raw material 5) (31.7g, 100mmol) it is dissolved in dichloromethane (300mL), DCC (20.7g it is sequentially added under ice bath, 100mmol), DMAP (12.3g, 100mmol), NMM (16.7mL, 150mmol), double benzyl ester hydrochlorate (the intermediate 11) (44.8g of glycyl aspartic acid, 110mmol), room temperature reaction 10 hours, solvent evaporated, residue with Ethyl acetate solvent, respectively with water, 5%HCl solution, 5%NaHCO3 solution, saturated nacl aqueous solution washs, organic layer anhydrous sodium sulfate is dried, filter, solvent evaporated, residue column chromatography purification, obtain light yellow solid 57.8g, yield 86%.
The preparation of embodiment 12 arginyl glycyl aspartic acid tripeptides (RGD)
Take the double benzyl ester hydrochlorate (intermediate 12) (18.2g, 30mmol) of arginyl glycyl aspartic acid and be dissolved in methanol (100mL), add Pd/C (2g), concentrated hydrochloric acid HCl (0.5mL), H2Displacement gas, under room temperature, logical hydrogen reacts 20 hours, terminates reaction, filters Pd/C, solvent evaporated, the white solid 9.5g of water/recrystallizing methanol, yield 91%, purity 99.6%.
Claims (10)
1. the preparation method of a RGD tripeptides, it is characterised in that comprise the following steps:
(1) with glycine as initiation material, under the effect of alkali, protect through tertbutyloxycarbonyl Boc, obtain Boc-glycine；
(2) Boc-glycine benzyl ester tosilate double with aspartic acid is condensed under the effect of condensing agent dicyclohexylcarbodiimide DCC/4-dimethylamino naphthyridine DMAP and organic base, obtains the double benzyl ester of Boc-glycyl aspartic acid；
(3) the double benzyl ester of Boc-glycyl aspartic acid sloughs Boc under trifluoracetic acid effect, obtains the double benzyl ester trifluoroacetate of glycyl aspartic acid；
(4) the double benzyl ester trifluoroacetate of glycyl aspartic acid and N-Boc-N'-NO2-L-arginine is condensed to yield the double benzyl ester of arginyl glycyl aspartic acid under the effect of condensing agent dicyclohexylcarbodiimide DCC/4-dimethylamino naphthyridine DMAP and organic base；
(5) the double benzyl ester of arginyl glycyl aspartic acid is taken off tertbutyloxycarbonyl under trifluoracetic acid effect and is obtained the double benzyl ester trifluoroacetate of arginyl glycyl aspartic acid；
(6) take off all protection groups through catalytic hydrogenation under arginyl glycyl aspartic acid double benzyl ester trifluoroacetate room temperature, normal pressure and obtain arginyl glycyl aspartic acid tripeptides RGD.
2. the preparation method of a RGD tripeptides, it is characterised in that step (1) reaction temperature is-5 ~ 40 DEG C, preferably 0 ~ 30 DEG C；Response time is 12 ~ 48 hours, preferably 24 hours；Solvent for use is water, organic solvent or a combination thereof, organic solvent can be selected for oxolane, dioxane etc., preferably water, alkali can enumerate sodium hydroxide, potassium hydroxide, Lithium hydrate, potassium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate, lithium carbonate, triethylamine, diethylisopropylamide, N-methylmorpholine etc., preferably sodium hydroxide and potassium hydroxide；Glycine and Boc2O mol ratio is 1:1 ~ 2, preferably 1:1.5.
3. the preparation method of a RGD tripeptides, it is characterised in that step (2) reaction temperature is 0 ~ 30 DEG C, the response time is 4 ~ 12 hours, preferably 6 ~ 8 hours；Solvent can enumerate dichloromethane, chloroform etc.；Organic base can enumerate N-methylmorpholine, triethylamine, diisopropylethylamine etc., the double benzyl ester tosilate of aspartic acid: Boc-glycine: DCC:DMAP: organic base mol ratio is 1:1 ~ 3:1 ~ 2:0.5 ~ 1.5:1 ~ 3, preferably 1:1.2 ~ 2.5:1 ~ 1.5:0.5 ~ 1:1.5 ~ 2.
4. the preparation method of a RGD tripeptides, it is characterised in that step (3) reaction temperature is room temperature, the response time is 0.5 ~ 4 hour, the preferred dichloromethane of solvent, dichloromethane: trifluoracetic acid volume ratio is 1:0.3 ~ 1.5, preferably 1:1.
5. the preparation method of a RGD tripeptides, it is characterised in that step (4) reaction temperature is 0 ~ 30 DEG C, the response time is 6 ~ 24 hours, preferably 10 ~ 14 hours；Solvent can enumerate dichloromethane, chloroform etc.；Organic base can enumerate N-methylmorpholine NMM, triethylamine, diisopropylethylamine etc.；N-Boc-N'-NO2-L-arginine: double benzyl ester trifluoroacetate: DCC:DMAP: the organic base mol ratio of glycyl aspartic acid is 1:1 ~ 3:1 ~ 2:0.5 ~ 1.5:1 ~ 3, preferably 1:1.2 ~ 2.5:1 ~ 1.5:0.5 ~ 1:1.5 ~ 2.
6. the preparation method of a RGD tripeptides, it is characterised in that step (5) reaction temperature is room temperature, the response time is 2 ~ 4 hours, the preferred dichloromethane of solvent, dichloromethane: trifluoracetic acid volume ratio is 1:0.3 ~ 1.5, preferably 1:1.
7. the preparation method of a RGD tripeptides, it is characterised in that step (6) reaction temperature is room temperature, the response time is 6 ~ 24 hours, and Pd/C consumption is the 5 ~ 30% of the double benzyl ester trifluoroacetate quality of arginyl glycyl aspartic acid, preferably 10%；Solvent may select water, organic solvent or a combination thereof, and organic solvent can enumerate methanol, ethanol, oxolane, glacial acetic acid, formic acid, dimethyl sulfoxide, dimethylformamide etc., preferably water, methanol, ethanol and oxolane.
8. the preparation method of a RGD tripeptides, it is characterised in that step (2) uses 1-ethyl-3-(3-dimethylamine propyl) carbodiimide hydrochloride EDCI/ I-hydroxybenzotriazole HOBt as condensing agent.
9. the preparation method of a RGD tripeptides, it is characterised in that step (4) uses 1-ethyl-3-(3-dimethylamine propyl) carbodiimide hydrochloride EDCI/ I-hydroxybenzotriazole HOBt as condensing agent.
10. the preparation method of a RGD tripeptides, it is characterised in that step (3) and step (5) saturated hydrochloric acid tetrahydrofuran solution, saturated hydrochloric acid dioxane solution or full or hydrochloric ethyl acetate solution removal Boc.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510243396.7A CN106146614A (en) | 2015-05-14 | 2015-05-14 | A kind of preparation method of RGD tripeptides |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510243396.7A CN106146614A (en) | 2015-05-14 | 2015-05-14 | A kind of preparation method of RGD tripeptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106146614A true CN106146614A (en) | 2016-11-23 |
Family
ID=57348053
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510243396.7A Pending CN106146614A (en) | 2015-05-14 | 2015-05-14 | A kind of preparation method of RGD tripeptides |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106146614A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018137679A1 (en) * | 2017-01-25 | 2018-08-02 | Teligene Ltd | Process for the Preparation of (10R) -7- (2-aminoacetyl) amino-12-fluoro-2, 10, 16-trimethyl-15-oxo-10, 15, 16, 17-tetrahydro-2H-8, 4- (metheno) pyrazolo [4, 3-h] [2, 5, 11] -benzoxadiazacyclotetradecine-3-carbonitrile |
| CN108484728A (en) * | 2018-03-23 | 2018-09-04 | 哈尔滨师范大学 | A kind of road Deng Su straight chains derivative, its preparation method and purposes |
| PL425131A1 (en) * | 2018-04-04 | 2019-10-07 | Uniwersytet Gdański | polyRGD peptides obtained by chemical and biotechnological method with antidemarcation and/or neuroprotective effect and a set for determination of their activity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250204A (en) * | 2010-05-19 | 2011-11-23 | 首都医科大学 | RGD sequence peptidyl methyl curcumin compounds, preparation method thereof, and application thereof |
| CN106046116A (en) * | 2016-06-28 | 2016-10-26 | 苏州大学 | Fc-FF-RGD composite as well as preparation method and application thereof |
-
2015
- 2015-05-14 CN CN201510243396.7A patent/CN106146614A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250204A (en) * | 2010-05-19 | 2011-11-23 | 首都医科大学 | RGD sequence peptidyl methyl curcumin compounds, preparation method thereof, and application thereof |
| CN106046116A (en) * | 2016-06-28 | 2016-10-26 | 苏州大学 | Fc-FF-RGD composite as well as preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 宋明媚: "化学法合成RGD三肽的研究", 《生物加工过程》 * |
| 邱凯: "RGD三肽的合成与生物活性检测", 《科学技术与工程》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018137679A1 (en) * | 2017-01-25 | 2018-08-02 | Teligene Ltd | Process for the Preparation of (10R) -7- (2-aminoacetyl) amino-12-fluoro-2, 10, 16-trimethyl-15-oxo-10, 15, 16, 17-tetrahydro-2H-8, 4- (metheno) pyrazolo [4, 3-h] [2, 5, 11] -benzoxadiazacyclotetradecine-3-carbonitrile |
| CN108484728A (en) * | 2018-03-23 | 2018-09-04 | 哈尔滨师范大学 | A kind of road Deng Su straight chains derivative, its preparation method and purposes |
| PL425131A1 (en) * | 2018-04-04 | 2019-10-07 | Uniwersytet Gdański | polyRGD peptides obtained by chemical and biotechnological method with antidemarcation and/or neuroprotective effect and a set for determination of their activity |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6350632B2 (en) | Method for producing peptide | |
| US9963483B2 (en) | Process for producing self-assembling peptide derivatives | |
| KR101467598B1 (en) | Process for hcv protease inhibitor intermediate | |
| CN107474107B (en) | Process for the preparation of GLYX-13 and compounds useful for the preparation of GLYX-13 | |
| CN106146614A (en) | A kind of preparation method of RGD tripeptides | |
| CN106188231B (en) | Synthesis and application of pasireotide pentapeptide intermediate | |
| ES2439246T3 (en) | Preparation procedure for (1R, 2S, 5S) -N - [(1S) -3-amino-1- (cyclobutylmethyl) -2,3-dioxopropyl] -3 - [(2S) -2 - [[[(1 , 1-dimethylethyl) amino] carbonyl] amino] -3,3-dimethyl-1-oxobutyl] -6,6-dimethyl-3-azabicyclo [3.1.0] hexane-2-carboxamide | |
| JP6011528B2 (en) | Method for producing peptide | |
| CN111978369B (en) | Method for preparing polypeptide | |
| CN108997187A (en) | A kind of preparation method of N (π)-methyl-L-histidine derivative and its application in synthesis whale carnosine | |
| CA2983559A1 (en) | Process for preparation of nitrogen mustard derivatives | |
| US20160017002A1 (en) | Process for Preparing Eptifibatide | |
| CN106699604B (en) | One seed sand library is than bent and its intermediate preparation method | |
| CN108440653A (en) | A kind of synthetic method of Buserelin compound | |
| Schabbert et al. | Incorporation of (2S, 3S) and (2S, 3R) β-Methyl aspartic acid into RGD-Containing peptides | |
| Ghalia et al. | Synthesis and Reactions of New Chiral Linear and Macrocyclic Tetraand Penta-peptide Candidates | |
| CN105418737B (en) | Solid-phase synthesis method and application of bregma cyclopeptide A | |
| WO2013131978A1 (en) | Process for the preparation of intermediates useful in the preparation of a viral protease inhibitor | |
| KR20160120345A (en) | Process for the liquid phase synthesis of h-inp-(d)bal-(d)trp-phe-apc-nh2, and pharmaceutically acceptable salts thereof | |
| CN114702547B (en) | Transmembrane polypeptides obtained by modification of amino acid side chains | |
| CN107698663B (en) | Liquid phase synthesis method of vilospiritide | |
| KR20030033001A (en) | Process for the preparation of 5-phenylpentanoyl-ala-argl-ala-[2-(3-amino-2-oxopyrrolidin-1-yl)propionyl]-ala-arg-ala-4-aminophenylacetamide | |
| Minta et al. | Easy saponification by metal silanolates: application in SPPS and in (S)-5-hydroxynorvaline preparation | |
| CN108864252B (en) | Method for preparing NRX-1074 | |
| CN109438363B (en) | Liquid-phase high-purity large-scale synthesis method of cyclic (leucyl-arginyl) dipeptide salt |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161123 |