Summary of the invention
Aiming at the problems existing in the prior art, the present invention provides a kind of compound, specially 2,3,4- triacetyl -1-
The synthetic method of (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside and hydrolysate.
The specific technical solution of the present invention is as follows:
2,3,4- triacetyl -1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside has knot shown in Formulas I
Structure:
1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside (5-BPT-AFU) has structure shown in Formula II:
1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside can be used as a kind of new fucoside zymolyte.
The present invention also provides the preparation sides of above compound 1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside
Method, synthetic technology route are as follows:
Using four acetylation fucoses and the bromo- 2- mercaptopyridine of 5- as starting material, with containing phosphinylidyne polymerization of olefin using catalyst functionalization from
Sub- liquid is reaction medium, using lewis' acid as catalyst, under microwave irradiation, carries out glycosylation reaction and is prepared 2,3,4-
Triacetyl -1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside, then 1- (5- bromo-2-pyridyl base) is obtained through hydrolysis
Sulfydryl-α-L- rock algae pyranoside.
Wherein, the molar ratio of four acetylation fucose of raw material and the bromo- 2- mercaptopyridine of 5- be 1:1~5, preferably 1:1~
3, it is further 1:1.
Phosphinylidyne polymerization of olefin using catalyst functionalized ion liquid (PFIL) of the present invention is the quaternary ammonium salt (PFIL-1) of having structure, season
Microcosmic salt (PFIL-2), pyridiniujm (PFIL-3), imidazole salts (PFIL-4), one in double phosphoryl functionalized imidazoles (PFIL-5)
Kind or a variety of mixtures:
Wherein, R1, R2, R3, R4=hydrogen, alkyl, alkoxy, aryl;N=1,2,3,4,5,6;X=(CF3SO2) N, PF6。
Preferably, R1, R2, R3, R4For hydrogen, methyl, ethyl, propyl, butyl, amyl, hexyl, alkoxy, phenyl.
As a preferred embodiment, ion liquid of quaternaries (PFIL-1), preferably R in the present invention1、R2=second
Oxygroup, phenyl;R3=ethyl, propyl, butyl.Preparation method is as follows, by triethylamine, tripropyl amine (TPA), tri-n-butylamine or triamylamine with
Bromo alkyl diphenyl phosphine oxide or bromo alkyl ethoxy phenyl phosphine oxide are 1: 1~1.2 mixing in molar ratio, are added organic
Solvent is placed in microwave reaction device, is 350W~500W in microwave power, reaction temperature is 80 DEG C~110 DEG C, when reaction
Between to be stirred to react under conditions of 60min~150min, obtain crude product, remove unreacting material, obtain quaternary ammonium bromide ion
Liquid.By the bis trifluoromethyl imine lithium or hexafluorophosphoric acid nak response of obtained quaternary ammonium bromide ionic liquid and equimolar amounts, obtain
To the ion liquid of quaternaries (PFIL-1), structure is as shown in formula III.
Quaternary phosphonium salt ionic liquid (PFIL-2), preferably R in the present invention1、R2=ethyoxyl, phenyl;R3=phenyl.It is made
Preparation Method is as follows: by triphenylphosphine and bromo alkyl diphenyl phosphine oxide, bromo alkyl phenyl-phosphonic acid ethyl ester or bromo alkylphosphines
Diethyl phthalate is 1: 1~1.2 mixing in molar ratio, and organic solvent is added, is placed in microwave reaction device, is in microwave power
350W~500W, reaction temperature are 80 DEG C~110 DEG C, and the reaction time to be stirred to react under conditions of 60min~150min, obtains
Crude product removes unreacting material, obtains quaternary phosphonium bromide ionic liquid.The quaternary phosphonium bromide ionic liquid and equimolar amounts that will be obtained
Bis trifluoromethyl imine lithium or hexafluorophosphoric acid nak response, obtain the quaternary phosphonium salt ionic liquid (PFIL-2), structure such as formula
Shown in IV.
Pyridine salt ionic liquid (PFIL-3), preferably R in the present invention1、R2=ethyoxyl, phenyl.Preparation method is such as
Under, by pyridine compounds and their and bromo alkyl diphenyl phosphine oxide, bromo alkyl phenyl-phosphonic acid ethyl ester or bromo alkyl phosphonic acid two
Ethyl ester is 1: 1~1.2 mixing in molar ratio, and organic solvent is added, is placed in microwave reaction device and is stirred to react, microwave power
For 350W~500W, reaction temperature is 80 DEG C~110 DEG C, and the reaction time is 60min~150min, obtains crude product, is removed not
Reaction raw materials obtain pyridinium tribromide ionic liquid.By the bis trifluoromethyl of obtained pyridinium tribromide ionic liquid and equimolar amounts
Imine lithium or hexafluorophosphoric acid nak response obtain the pyridine salt ionic liquid (PFIL-3), and structure is shown as a formula V.
Imidazolium ionic liquid (PFIL-4), preferably R in the present invention1=methyl, ethyl, propyl, butyl, amyl, hexyl;
R2=hydrogen;R3、R4=ethyoxyl, phenyl.Preparation method is as follows: by glyoxaline compound and bromo alkyl diphenyl phosphine oxide,
Bromo alkyl phenyl-phosphonic acid ethyl ester or bromo alkyl diethyl phosphonate are 1: 1~1.2 mixing in molar ratio, are placed in microwave reaction
It is 280W~500W in microwave power in device, reaction temperature is 80 DEG C~120 DEG C, and the reaction time is 60min~150min,
Crude product is obtained, unreacting material is removed, obtains imidazoles bromide ionic liquid.By obtained imidazoles bromide ionic liquid with etc. rub
The bis trifluoromethyl imine lithium or hexafluorophosphoric acid nak response of your amount, obtain the imidazole salt ionic liquid (PFIL-4), structure
As shown in Formula IV.
Double phosphoryl functionalized imidazole ionic liquids (PFIL-5), preferably R in the present invention1、R2=ethyoxyl, phenyl.'s
The preparation method is as follows: by imidazoles and bromo alkyl diphenyl phosphine oxide, bromo alkyl phenyl-phosphonic acid ethyl ester or bromo alkyl phosphonic acid
Diethylester is dissolved in organic solvent with the molar ratio of 1:2~4, adds water soluble carbonate, is then placed into microwave reaction dress
Middle carry out microwave reaction is set, microwave power is 280~500W, and reaction temperature is 80~110 DEG C, and the reaction time is 5~40min,
Crude product is obtained after reaction, removes unreacted raw material, anion exchanger is added in the crude product, carries out anion exchange,
Double phosphoryl functionalized imidazole ionic liquids (PFIL-5) are obtained, structure is as shown in Formula VII.
The lewis' acid include nickel salt, mantoquita, molysite, pink salt or scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium,
Dysprosium, holmium, erbium, ytterbium, lutetium salt.
The salt includes villaumite, sulfate, nitrate, fluoroform sulphonate or hexafluorophosphate.
For example, lewis' acid is ferric trichloride, tin tetrachloride, ytterbium nitrate, trifluoromethanesulfonic acid neodymium etc. in the present invention.
The present invention is catalyzed reaction in microwave-assisted lower progress.The power that microwave can be adjusted according to the degree of reaction is timely
Between.In the present invention, microwave power is preferably 200~700W, is further 300~600W, further for 350~
500W.In a preferred embodiment of the present invention, it is irradiated using intermittent type microwave, i.e. 3~10min of irradiation, rests 0.5~2min
Circulation irradiation.4~8min is preferably irradiated, rests 1~1.5min.Catalytic temperature be 35 DEG C~90 DEG C, preferably 40 DEG C~
60 DEG C, be further 45 DEG C~55 DEG C.
It further include alkyl chloride in reaction medium, i.e., with phosphinylidyne polymerization of olefin using catalyst functionalization in above-mentioned catalysis reaction of the invention
The mixed solvent of ionic liquid and chloralkane is as reaction medium.Wherein, chloralkane is methylene chloride, chloroform and 1,
One of 2- dichloroethanes or a variety of mixtures.The present invention does not limit phosphoryl coordination functionalized ion liquid and alkyl chloride
The usage ratio of hydrocarbon, using the arbitrary proportion containing phosphinylidyne polymerization of olefin using catalyst functionalized ion liquid protection scope of the present invention it
It is interior.It is preferred that the volume ratio of phosphinylidyne polymerization of olefin using catalyst functionalized ion liquid and chloralkane be 0.2~0.8:10~20, further for
0.3~0.7:13~18 are further 0.5:15.
It further include general ionic liquid in reaction medium, i.e., with phosphinylidyne polymerization of olefin using catalyst in above-mentioned catalysis reaction of the invention
The mixed solvent of general ionic liquid in functionalized ion liquid and this field is as reaction medium.Wherein general ionic liquid
For commercial goods dialkylimidazolium salt, the alkyl of the dialkylimidazolium salt be methyl, ethyl, propyl, butyl, amyl, oneself
Base, the anion of the dialkylimidazolium salt are bis trifluoromethyl imines ion or hexafluorophosphate ion.The present invention does not limit phosphorus
Acyl group be coordinated functionalized ion liquid and general ionic liquid usage ratio, using contain phosphinylidyne polymerization of olefin using catalyst functionalization ionic liquid
The arbitrary proportion of body is within the scope of the present invention.It is preferred that phosphinylidyne polymerization of olefin using catalyst functionalized ion liquid and conventional ion liquid
The volume ratio of body is 1:1~20, is further 1:4~10, is further 1:5.
The lower reaction of catalysis obtains 2,3,4- triacetyl -1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside
Afterwards, 2,3,4- triacetyl -1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside is preferably in the first containing sodium methoxide
Hydrolysis obtains 1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside in alcohol.1- (the 5- bromo-2-pyridyl being prepared
Base) sulfydryl-α-L- rock algae pyranoside can be used as substrate and is used to prepare fucosidase diagnostic reagent.
Beneficial effects of the present invention are as follows:
(1) present invention is complexed with lewis' acid catalyst metals center using coordination functionalized ion liquid, is passed through change
Functionalized ion liquid structure, to regulate and control the steric hindrance size of metal ion center, to change the solid of glycosylation reaction
Selectivity;
(2) microwave heating reaction be material in electromagnetic field since dielectric loss generates fuel factor, have heating response it is fast,
The features such as being heated simultaneously inside and outside substance.And ionic liquid has very high polarizability, is a kind of good microwave absorbing material.By same
When use microwave heating technique and ion liquid medium, accelerate heating speed, make reaction more evenly, it is high-efficient.
(3) functionalized ion liquid used in is not only used as reaction medium, but also as metal-ion ligand, has both two kinds of functions.
The starting material of 1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside preparation method of the invention is opposite
Cheaply, synthesizing mean is simple, quick.2,3,4- triacetyl -1- (5- bromo-2-pyridyl base) sulfydryl-α-L- rock algae of the invention
Used functionalized ion liquid may be reused pyranoside during the preparation process, further reduce costs.With 1- (5-
Bromo-2-pyridyl base) sulfydryl-α-L- rock algae pyranoside cost for preparing fucosidase diagnostic reagent as substrate is low,
Be conducive to effective universal use of fucosidase diagnostic reagent.