CN105806820B - A kind of continuous flow synthetic method of glycoprotein fluorescent probe molecule - Google Patents
A kind of continuous flow synthetic method of glycoprotein fluorescent probe molecule Download PDFInfo
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- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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Abstract
The invention discloses a kind of continuous flow synthetic methods of glycoprotein fluorescent probe molecule, belong to organic synthesis applied technical field.The reaction of the present invention is carried out in the pipeline reactor continuously flowed, and specific surface area is very big, has fabulous heat exchange and mass-transfer efficiency, and raw material can be made by accurate proportioning moment mixing, the advantageous yield and quality for improving product.The synthetic method of the present invention, has the characteristics that easy purification, high conversion rate, continuous safety, reaction condition accurately control, and energy is safe and environment-friendly, efficiently productive target fluorescent molecular XC DAPOL CPBA.The reaction system of the present invention is safely controllable, reacts under normal pressure, reaction yield 20~61%, purity can reach 95%.
Description
Technical field
The present invention relates to a kind of continuous flow synthetic methods of glycoprotein fluorescent probe molecule, belong to organic synthesis application technology
Field.
Background technology
Glycoprotein is prevalent in animal, plant and microorganism, and type is various, and function is extensive, in molecular recognition and carefully
It plays a decisive role in born of the same parents' identification, with many diseases such as infection, tumour, cardiovascular disease, hepatopathy, nephrosis, diabetes and certain
Generation, the development of genetic disease etc. are related.The glycoprotein " falling off " on disease-inflicted cells surface is to ambient enviroment or enters blood circulation,
Information can be provided for clinical diagnosis as abnormality mark object, contribute to the judgement of diagnosis or prognosis.
Optical molecular image (Optical Molecular Imaging) is a popular neck of Medical Imaging research
Domain represents the direction of future biological diagnostic reagent development；In recent years, important tool --- the fluorescence of optical molecular image research
Probe is more and more applied to each field such as clinical medicine, biology, becomes the spy of cell biology and biomedical research
Kind reagent and diagnostic medicine.It is that academic circles at present and industrial quarters use comparative maturity using Rhodmine as raw material boy's fluorescence probe
A kind of diagnosing image technology.Its operation principle is that fluorescent molecular is linked with boronic acid compounds, is formed and turns electronics based on photoinduction
The fluorescence probe that principle of transfer generates discharges fluorescence (as shown in Figure 1), reaches after the probe and glycoprotein completion molecular recognition
To diagnostic purpose.
Acid reagent XC-DAPOL-CPBA (structural formula is as shown in Figure 2) containing Rhodmine is to prepare glycoprotein diagnosis examination
The crucial fluorescent molecular of agent, says from synthetic degree of angle, it is known that document there are the purifying of product difficulty, low yield, can not mass produce
Problem, there is an urgent need to develop new production technology.Different from traditional intermittent chemistry, continuous flow chemistry is to be with microreactor
Micro- Chemical Engineering Technology on basis, has many characteristics, such as mobile, micromation and greenization.Microreactor is led in diagnostic reagent study on the synthesis
The utilization in domain is just rarer.
Invention content
The purpose of the present invention is to propose to it is a kind of can overcome prior art defect XC-DAPOL- is prepared in a manner of continuous flow
The process of CPBA.The present invention utilizes continuous flow reaction technology, is carried out to the synthesis technology of fluorescent molecular XC-DAPOL-CPBA
It improves, improves combined coefficient.
It is with continuous the present invention provides a kind of preparation method of glycoprotein fluorescent probe molecule XC-DAPOL-CPBA
Boronic acid compounds 1 and compound 2 are condensed to yield activation ester compounds 3 by stream series connection chemical reaction technology, then with amino chemical combination
Compound 5 is obtained by the reaction in object 4, is most protected afterwards through taking off tertbutyloxycarbonyl (Boc), target fluorescent is condensed to yield with chloride compounds 7
Molecule XC-DAPOL-CPBA.
The chemical formula of each compound is as follows：
In one embodiment of the invention, the preparation method, specific steps：(1) first by the molten of boronic acid compounds 1
Liquid and the solution of compound 2 pass through metering pump P1, P2 respectively, squeeze into pre-mix module M1 according to certain proportioning and are mixed；
(2) and then in reaction module R1 it reacts；(3) then compound 4 squeezes into pre-mix module M2 by metering pump P3, with chemical combination
Object 3 mixes, and is and then reacted in reaction module R2, obtains compound 5；(4) then trifluoroacetic solution is beaten through metering pump P4
Enter pre-mix module M3, mixed with compound 5, is reacted later in reaction module R3, obtain compound 6；(5) then compound 7 is logical
It crosses metering pump P5 and squeezes into pre-mix module M4, mixed with compound 6, reacted in reaction module R4；(6) finally in product collection module
Efflux is collected in P.
In one embodiment of the invention, the boronic acid compounds 1 and compound 2, compound 4, compound 7 are rubbed
Your ratio is 1:1:1:1, which can guarantee that raw material fully reacts.
In one embodiment of the invention, the reaction dissolvent be dichloromethane, ethyl acetate, tetrahydrofuran,
Any one in DMF.
In one embodiment of the invention, the temperature condition of the reaction be 30~90 DEG C, the reaction time be 10~
20 minutes.
In one embodiment of the invention, the compound 1, compound 2, the concentration of compound 4 and flow velocity difference
For 0.01mmol/mL, 0.1-0.2mL/min.
In one embodiment of the invention, the solvent is ethyl acetate solution, in reaction module R1, R2, R4
Residence time be 20 minutes, reaction temperature is 60 degree.
In one embodiment of the invention, reactant is 20 minutes in the stop of reaction module R3, reaction module R3
Reaction temperature be 30 degree.
Beneficial effects of the present invention：
(1) there is synthetic method provided by the invention easy purification, high conversion rate, continuous safety, reaction condition to accurately control
The features such as, it can safe and environment-friendly, efficiently productive target fluorescent molecular XC-DAPOL-CPBA.The reaction system is safely controllable normal
Pressure reaction, reaction yield 20~61%, purity can reach 95%.
(2) reaction of the invention is carried out in the pipeline reactor continuously flowed, and specific surface area is very big, tool
There are fabulous heat exchange and mass-transfer efficiency, raw material can be made by accurate proportioning moment mixing, the advantageous yield and matter for improving product
Amount.
Description of the drawings
Fig. 1：The operation principle of the fluorescence probe of glycoprotein；
Fig. 2：The chemical constitution of XC-DAPOL-CPBA；
Fig. 3：Fluorescent molecular XC-DAPOL-CPBA's is continuously synthesizing to route；Wherein 1 is compound 1, A is compound 2, B
For compound 4, C be TFA (trifluoroacetic acid), D it is compound 7；M1, M2, M3, M4 are pre-mix module；P1, P2, P3, P4, P5 are
Metering pump；R1, R2, R3, R4 are reaction module；P is product collection module；
Fig. 4：Prepare the reaction equation of XC-DAPOL-CPBA.
Specific implementation mode
Embodiment 1：The present invention's is continuously synthesizing to flow
With reference to the industrial flow of Fig. 3 present invention, as steps described below：(1) first by the solution of boric acid 1 and compound 2
Solution passes through P1, P2 metering pump, squeezes into mixing module M1 according to certain proportioning and is mixed；(2) and then in R1 occur anti-
Ying Hou, (3) then compound 4 squeezes into module M2 by metering pump, is mixed with Acibenzolar 3, is and then reacted in reaction module R2,
Compound 5 is obtained, (4) then trifluoroacetic solution squeezes into module M3 through metering pump, mixes with compound 5, is reacting later
Module R3 reactions, obtain compound 6, and (5) then compound 7 squeezes into module M4 by metering pump, is mixed with compound 6, anti-
Module R4 is answered to react, (6) efflux is finally collected in collection module P.
Embodiment 2
(1) equipment therefor：Determine micro passage reaction connection mode with reference to Fig. 3, hybrid reaction number of modules according to flow velocity with
Reaction time determines that heat transferring medium is water.
(2) dichloromethane of dichloromethane solution (0.01mmol/mL, flow velocity 0.2mL/min) and compound 2 of compound 1
Alkane solution (0.01mmol/mL, flow velocity 0.2mL/min) mixes (30 degree of temperature) in mixed cell M1, is stopped 10 minutes in R1
(30 degree of temperature), it is then mixed with the dichloromethane solution of compound 4 (0.01mmol/mL, flow velocity 0.2mL/min) in module M2
It closes, is stopped in R2 10 minutes (30 degree of temperature), dichloromethane solution (0.01mmol/mL, the flow velocity 0.2mL/min) warp of TFA
Metering pump squeezes into mixing module M3, and then stops 10 minutes (30 degree of temperature) in reaction module R3, efflux is mixing later
Module M4 is mixed with the dichloromethane solution of compound 7 (0.01mmol/mL) and triethylamine (0.02mmol/mL), in reaction mould
Block R4 stops 10 minutes (30 degree of temperature), and last mixed liquor flows into the collection module P containing ether, and solid is precipitated.It filters solid
Body, is then washed with water, ethyl alcohol is washed, and drying obtains blue solid (15mg, four step gross production rates 20%).
Embodiment 3
The tetrahydrofuran solution (0.01mmol/mL, flow velocity 0.2mL/min) of compound 1 and the tetrahydrofuran of compound 2 are molten
Liquid (0.01mmol/mL, flow velocity 0.2mL/min) mixes (60 degree of temperature) in mixed cell M1, and 10 minutes (temperature are stopped in R1
60 degree), then mixed with the tetrahydrofuran solution of compound 4 (0.01mmol/mL, flow velocity 0.2mL/min) in module M2,
10 minutes (60 degree of temperature) is stopped in R2, the tetrahydrofuran solution (0.01mmol/mL, flow velocity 0.2mL/min) of TFA is through metering pump
Mixing module M3 is squeezed into, and then stops 10 minutes (30 degree of temperature) in reaction module R3, efflux is in mixing module M4 later
It mixes with the tetrahydrofuran solution of compound 7 (0.01mmol/mL) and triethylamine (0.02mmol/mL), stops in reaction module R4
It stays 10 minutes (60 degree of temperature), last mixed liquor flows into the collection module P containing ether, and solid is precipitated.Solid is filtered, then
Be washed with water, ethyl alcohol is washed, drying obtain blue solid (20mg, four step gross production rates 27%).
Embodiment 4
The ethyl acetate solution (0.01mmol/mL, flow velocity 0.2mL/min) of compound 1 and the ethyl acetate of compound 2 are molten
Liquid (0.01mmol/mL, flow velocity 0.2mL/min) mixes (60 degree of temperature) in mixed cell M1, and 10 minutes (temperature are stopped in R1
60 degree), then mixed with the ethyl acetate solution of compound 4 (0.01mmol/mL, flow velocity 0.2mL/min) in module M2,
10 minutes (60 degree of temperature) is stopped in R2, the ethyl acetate solution (0.01mmol/mL, flow velocity 0.2mL/min) of TFA is through metering pump
Mixing module M3 is squeezed into, and then stops 10 minutes (30 degree of temperature) in reaction module R3, efflux is in mixing module M4 later
It mixes with the ethyl acetate solution of compound 7 (0.01mmol/mL) and triethylamine (0.02mmol/mL), stops in reaction module R4
It stays 10 minutes (60 degree of temperature), last mixed liquor flows into the collection module P containing ether, and solid is precipitated.Solid is filtered, then
Be washed with water, ethyl alcohol is washed, drying obtain blue solid (35mg, four step gross production rates 47%).
Embodiment 5
The DMF solution of DMF solution (0.01mmol/mL, flow velocity 0.2mL/min) and compound 2 of compound 1
(0.01mmol/mL, flow velocity 0.2mL/min) mixes (90 degree of temperature) in mixed cell M1, and 10 minutes (temperature 90 are stopped in R1
Degree), it then mixes with the DMF solution of compound 4 (0.01mmol/mL, flow velocity 0.2mL/min) in module M2, stops in R2
10 minutes (90 degree of temperature), the DMF solution (0.01mmol/mL, flow velocity 0.2mL/min) of TFA is stayed to squeeze into hybrid guided mode through metering pump
And then block M3 stops 10 minutes (90 degree of temperature) in reaction module R3, efflux is in mixing module M4 and compound 7 later
The DMF solution of (0.01mmol/mL) and triethylamine (0.02mmol/mL) mixes, and 10 minutes (temperature 90 are stopped in reaction module R4
Degree), last mixed liquor flows into the collection module P containing ether, and solid is precipitated.Solid is filtered, is then washed with water, ethyl alcohol is washed,
Drying obtains blue solid (25mg, four step gross production rates 34%).
Embodiment 6
The ethyl acetate solution (0.01mmol/mL, flow velocity 0.1mL/min) of compound 1 and the ethyl acetate of compound 2 are molten
Liquid (0.01mmol/mL, flow velocity 0.1mL/min) mixes (60 degree of temperature) in mixed cell M1, and 20 minutes (temperature are stopped in R1
60 degree), then mixed with the ethyl acetate solution of compound 4 (0.01mmol/mL, flow velocity 0.1mL/min) in module M2,
20 minutes (60 degree of temperature) is stopped in R2, the ethyl acetate solution (0.01mmol/mL, flow velocity 0.1mL/min) of TFA is through metering pump
Mixing module M3 is squeezed into, and then stops 20 minutes (30 degree of temperature) in reaction module R3, later 7 (0.01mmol/ of compound
ML) and the ethyl acetate solution of triethylamine (0.02mmol/mL) squeezes into (flow velocity 0.1mL/min) with efflux mixed through metering pump
Block M4 mixing is molded, stops 20 minutes (60 degree of temperature) in reaction module R4, last mixed liquor flows into the collection mould containing ether
In block P, solid is precipitated.Solid is filtered, is then washed with water, ethyl alcohol is washed, drying obtains blue solid (45mg, four step gross production rates
61%).
Although the present invention has been described by way of example and in terms of the preferred embodiments, it is not limited to the present invention, any to be familiar with this skill
The people of art can do various change and modification, therefore the protection model of the present invention without departing from the spirit and scope of the present invention
Enclosing be subject to what claims were defined.
Claims (16)
1. a kind of preparation method of glycoprotein fluorescent probe molecule XC-DAPOL-CPBA is with continuous flow series connection chemical reaction
Boronic acid compounds 1 and compound 2 are condensed to yield activation ester compounds 3 by technology, then with 4 being obtained by the reaction of amino-compound
Object 5 is closed, most protects to obtain compound 6 through taking off tertbutyloxycarbonyl afterwards, compound 6 is condensed to yield target fluorescent with chloride compounds 7
Molecule XC-DAPOL-CPBA；
The chemical formula of wherein each compound is as follows：
2. preparation method according to claim 1, which is characterized in that the preparation method, specific steps：(1) first by boron
The solution of acid compound 1 and the solution of compound 2 pass through metering pump P1, P2 respectively, and premix mould is squeezed into according to certain proportioning
Block M1 is mixed；(2) and then in reaction module R1 it reacts；(3) then compound 4 squeezes into premix by metering pump P3
Module M2 is mixed with compound 3, is and then reacted in reaction module R2, is obtained compound 5；(4) subsequent trifluoroacetic solution
Pre-mix module M3 is squeezed into through metering pump P4, is mixed with compound 5, is reacted later in reaction module R3, obtains compound 6；(5) with
Compound 7 squeezes into pre-mix module M4 by metering pump P5 afterwards, is mixed with compound 6, is reacted in reaction module R4；(6) finally exist
Efflux is collected in product collection module P.
3. preparation method according to claim 2, which is characterized in that the boronic acid compounds 1 and compound 2, compound
4, the ratio of compound 7 is 1:1:1:1.
4. preparation method according to claim 2, which is characterized in that reaction dissolvent used in the preparation method is two
Any one in chloromethanes, ethyl acetate, tetrahydrofuran, DMF.
5. preparation method according to claim 2, which is characterized in that the temperature condition of the reaction in the reaction module is
30~90 DEG C, the reaction time is 10~20 minutes.
6. preparation method according to claim 2, which is characterized in that the compound 1, compound 2, compound 4 it is dense
Degree and flow velocity are respectively 0.01mmol/mL, 0.1-0.2mL/min.
7. preparation method according to claim 2, which is characterized in that reaction dissolvent used in the preparation method is second
Acetate solution, the residence time in reaction module R1, R2, R4 are 20 minutes, and reaction temperature is 60 degree.
8. preparation method according to claim 2, which is characterized in that the stop of the reaction in the reaction module R3 is 20
Minute, the reaction temperature of reaction module R3 is 30 degree.
9. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 1.
10. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 2.
11. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 3.
12. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 4.
13. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 5.
14. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 6.
15. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 7.
16. the glycoprotein fluorescent probe molecule XC-DAPOL-CPBA that method obtains according to claim 8.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02129551A (en) * | 1988-11-10 | 1990-05-17 | Snow Brand Milk Prod Co Ltd | Method for determining alpha1-acid glycoprotein |
| CN1531654A (en) * | 2001-04-24 | 2004-09-22 | ������˹-ϣ���¹�˾ | Haemoglobin assay |
| CN1846844A (en) * | 2005-03-29 | 2006-10-18 | 株式会社东芝 | Method for manufacturing multiple-phase particle and apparatus for manufacturing multiple-phase particle |
| CN103145777A (en) * | 2013-03-04 | 2013-06-12 | 华东理工大学 | Rhodamine carbohydrate and application thereof |
| CN104262991A (en) * | 2014-09-17 | 2015-01-07 | 山西青山化工有限公司 | Method for semi-continuous production of fluorescent whitening agent |
| CN104483295A (en) * | 2014-11-27 | 2015-04-01 | 陕西师范大学 | Method for detecting glycoprotein by molecularly imprinted microspheres based on boric acid fluorescence probe |
| CN105400506A (en) * | 2015-08-31 | 2016-03-16 | 泰山学院 | [2.2]cyclophane-based rhodamine Hg<2+> fluorescent probe and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631364A (en) * | 1994-03-31 | 1997-05-20 | Axis Biochemicals Asa | Labelled boronic acid derivatives |
-
2016
- 2016-05-11 CN CN201610308732.6A patent/CN105806820B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02129551A (en) * | 1988-11-10 | 1990-05-17 | Snow Brand Milk Prod Co Ltd | Method for determining alpha1-acid glycoprotein |
| CN1531654A (en) * | 2001-04-24 | 2004-09-22 | ������˹-ϣ���¹�˾ | Haemoglobin assay |
| CN1846844A (en) * | 2005-03-29 | 2006-10-18 | 株式会社东芝 | Method for manufacturing multiple-phase particle and apparatus for manufacturing multiple-phase particle |
| CN103145777A (en) * | 2013-03-04 | 2013-06-12 | 华东理工大学 | Rhodamine carbohydrate and application thereof |
| CN104262991A (en) * | 2014-09-17 | 2015-01-07 | 山西青山化工有限公司 | Method for semi-continuous production of fluorescent whitening agent |
| CN104483295A (en) * | 2014-11-27 | 2015-04-01 | 陕西师范大学 | Method for detecting glycoprotein by molecularly imprinted microspheres based on boric acid fluorescence probe |
| CN105400506A (en) * | 2015-08-31 | 2016-03-16 | 泰山学院 | [2.2]cyclophane-based rhodamine Hg<2+> fluorescent probe and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 微通道连续流反应器用于传统搅拌釜的工艺改造;谷杰等;《现代化工》;20120331;第32卷(第3期);第71-73、75页 * |
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