CN108484901A - A kind of method that thermal polycondensation prepares the polylysine of the linear epsilon-polylysine of high-content - Google Patents
A kind of method that thermal polycondensation prepares the polylysine of the linear epsilon-polylysine of high-content Download PDFInfo
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- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
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Abstract
The present invention provides a kind of method that thermal polycondensation prepares the polylysine of the linear ε polylysines of high-content, belongs to Macroscopic single crystal and anti-biotic material field.Solve the problems, such as in the prior art by thermal polycondensation at branched polylysine in linear ε polylysine contents it is relatively low.This method is first to be protected to the α amino of lysine using dynamic protection group, and the lysine monomer of dynamic protection radical protection is made；The dynamic protection group is the blocking group that unstable amido bond, imine linkage can be formed with the α amino of lysine；Then the lysine monomer of dynamic protection radical protection is ground with alkali, catalyst reaction is added, obtains the polylysine of the linear ε polylysines of high-content.Preparation method provided by the invention is starting material using the lysine of cheap reproducible, and at low cost, operation is simple, and in the branched polylysine of acquisition, the content of linear ε polylysines can be more than 80%.
Description
Technical field
The invention belongs to Macroscopic single crystal and anti-biotic material fields, and in particular to a kind of thermal polycondensation prepares the linear ε-of high-content
The method of the polylysine of polylysine.
Background technology
Epsilon-polylysine is the cationic polyaminoacids being formed by connecting with α-carboxyl by the epsilon-amino of lysine monomer, peace
Atoxic, it is biodegradable and have excellent anti-microbial property, be widely used in food preservative and cosmetics addition
The fields such as agent.The epsilon-polylysine being commercialized at present is mainly derived from microbe fermentation method, and production process is complicated, cost is higher
And molecular weight is relatively low (less than 4000), limits its application.
On the other hand, in recent years, there is the booming new situation in the production of amino acid.By taking lysine as an example, only in
State produces lysine per year just more than 2,000,000 tons.Therefore, new polymerization is explored, is height by reproducible lysine resource conversion
The polyaminoacid of added value has great importance.
Currently, the correlative study for synthesizing epsilon-polylysine with chemical method is still less.In document [Chemical
Science, 2015,6,6385-6391], [Macromolecules, 2017,50,9128-9134] and Chinese patent
The ring-opening polymerisation based on lactams and special protection group are provided in ZL201510047405.5, and it is poly- to prepare high molecular weight ε-
The method of lysine.But its polymerizing condition is harsh, and needs by processes such as complicated protections and deprotection.
Thermal polycondensation can prepare poly- amino directly using amino acid as starting material by the polycondensation between amino and carboxyl
Acid, prepares and deprotection without complicated monomer, have it is easy to operate, of low cost, be suitable for industrialized production
The features such as, it is by the effective way for the polyaminoacid that cheap, reproducible amino acid resource conversion is high added value.Lysine has
There are one carboxyl, two amino, belong to AB2Type monomer directly carries out thermal polycondensation if do not protected to it, can only obtain branched
Polylysine, including end monomer unit (T), branched monomer unit (D) and linear monomer unit (L) three parts, wherein line
Property monomeric unit again include linear α-polylysine (Lα) and linear epsilon-polylysine (Lε) two parts.Rely as Klok et al. is utilized
Propylhomoserin hydrochloride directly carries out thermal polycondensation, obtains hyperbranched poly lysine [Journal of Polymer Science:Part
A:Polymer Chemistry, 2007,45,5494-5508], wherein the content of linear epsilon-polylysine is about 53%.Text
It offers in [Macromolecules, 2007,40,5726-5734], also reports the side that a kind of thermal polycondensation prepares branched polylysine
Method, wherein the content of linear epsilon-polylysine is only 39%.Currently, the branched poly- bad ammonia prepared by the direct thermal polycondensation of lysine
In acid, the content of epsilon-polylysine is relatively low.
Branched polylysine all has potential application value in fields such as biomedical and industrial productions.Document
In [Macromolecular Bioscience 2012,12,794-804], it was recently reported that using branched polylysine as gene
The research of transfection reagent.Document [Journal of the Chemical Society, Chemical Communications
1990,8-9] in, it was recently reported that using branched polylysine as the research of multiple antigenic peptide.Document [Pharmaceutical
Research 1998,15,776-782] in, it has synthesized a kind of branched polylysine and has had studied it in terms of drug delivery
Using.In 107349434 A of patent CN, it was recently reported that branched polylysine is utilized to be used for magnetic resonance as contrast agent carrier platform
Research in terms of imaging.In patent CN103917623A, it was recently reported that using branched polylysine as the research of shale control agent.
But by the branched polylysine prepared by thermal polycondensation, be easy to cause because being excessively crosslinked its dissolubility and biocompatibility compared with
Difference limits its application to a certain extent.On the other hand, linear epsilon-polylysine it is safe and non-toxic, with excellent antibiotic property
Can, improve content of the linear epsilon-polylysine in branched polylysine, it will help improve the dissolubility of branched polylysine
And biocompatibility, and its application in daily use chemicals and field of food will be expanded, there is important industrial value.But according to us
It is known, so far, in addition to Chinese patent ZL201510047405.5 and document [Chemical Science, 2015,6,
6385-6391] and document [Macromolecules, 2017,50,9128-9134] in reported prepared by ring-opening polymerisation
Outside linear epsilon-polylysine, thermal polycondensation there is no to prepare the report of High Linear epsilon-polylysine content polylysine.
Invention content
The purpose of the present invention is to solve in the prior art by thermal polycondensation at branched polylysine in linear ε-it is poly-
The relatively low problem of lysine content provides the side that a kind of thermal polycondensation prepares the polylysine of the linear epsilon-polylysine of high-content
Method.
In order to solve the above technical problems, technical scheme is as follows：
A kind of method that thermal polycondensation prepares the polylysine of the linear epsilon-polylysine of high-content, this method include：
Step 1：The α amino of lysine is protected using dynamic protection group, obtains dynamic protection radical protection
Lysine monomer；
The dynamic protection group is the guarantor that unstable amido bond, imine linkage can be formed with the α amino of lysine
Protect group；
Step 2：The lysine monomer for the dynamic protection radical protection that step 1 obtains is ground with alkali, 100
Under the conditions of DEG C -250 DEG C, catalyst is added, is stirred to react 1-72h, be cooled to room temperature termination reaction, washing drains, obtains height and contain
Measure the polylysine of linear epsilon-polylysine.
Preferably, the dynamic protection group is selected from benzyloxycarbonyl group, tertbutyloxycarbonyl, fluorenylmethyloxycarbonyl, allyl oxygen
Carbonyl, methoxycarbonyl group, carbethoxyl group, trimethylsilyl ethoxycarbonyl, phthalyl, p-toluenesulfonyl, trifluoroacetyl group,
One or more of adjacent (to) nitrobenzenesulfonyl, pivaloyl group, benzoyl, benzaldehyde or isobutylaldehyde.
Preferably, the step one is specially：L-lysine mono-hydrochloric salts and alkali are added in the reaction vessel, then
It adds dynamic protection group or the compound containing dynamic protection group is reacted, obtain relying for dynamic protection radical protection
Propylhomoserin monomer；
Preferably, the reaction temperature of the step one is 0 DEG C -150 DEG C, reaction time 1h-24h.
Preferably, the alkali is sodium hydroxide, potassium hydroxide, triethylamine, potassium carbonate, sodium carbonate, concentrated ammonia liquor or pyrrole
It is one or more in pyridine.
Preferably, the alkali in the step two is lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, carbonic acid
It is one or more in potassium, sodium carbonate, potassium tert-butoxide or sodium tert-butoxide.
Preferably, in the step two the lysine monomer of dynamic protection radical protection and the alkali molar ratio
It is 1:(0.5-5).
Preferably, the catalyst in the step two has following general formula：
MLx
Wherein, M be titanium, zirconium, hafnium, scandium, yttrium, cobalt, nickel, palladium, antimony, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, rhenium, iron, ruthenium, osmium,
One or more of rhodium, iridium, gold, platinum, silver, copper, zinc, cadmium, boron, aluminium, lanthanum, samarium, cerium, neodymium or ytterbium；
L is fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, methoxyl group, ethyoxyl, the third oxygen
One or more of base, isopropoxy, butoxy, tert-butoxy, acetate, propionyloxy, isopropyl acidic group or butyric acid base；X is
The integer of 1-6.
Preferably, catalyst accounts for the lysine monomer of the dynamic protection radical protection and rubs in the step two
The 0.05%-8% of your score.
Preferably, the washing in the step 2 is first to be washed with methanol, is filtered, and removes insoluble matter, is washed with water and washs,
It filters and removes insoluble matter.
Beneficial effects of the present invention
The present invention provides a kind of method that thermal polycondensation prepares the polylysine of the linear epsilon-polylysine of high-content, and this method is
By protecting the α amino of lysine, the lysine monomer of dynamic protection radical protection is made, then pass through thermal polycondensation, system
It is standby go out High Linear epsilon-polylysine content polylysine.It compares with the prior art, preparation method provided by the invention uses
The lysine of cheap reproducible is starting material, and at low cost, operation is simple, in the branched polylysine of acquisition, linear ε-
The content of polylysine can be more than 80%, have good application value in daily use chemicals and field of food.
Specific implementation mode
A kind of method that thermal polycondensation prepares the polylysine of the linear epsilon-polylysine of high-content, this method include：
Step 1：The α amino of lysine is protected using dynamic protection group, obtains dynamic protection radical protection
Lysine monomer；
The dynamic protection group is the guarantor that unstable amido bond, imine linkage can be formed with the α amino of lysine
Protect group；
Step 2：The lysine monomer for the dynamic protection radical protection that step 1 obtains is ground with alkali, 100
Under the conditions of DEG C -250 DEG C, catalyst is added, is stirred to react 1-72h, be cooled to room temperature termination reaction, washing drains, obtains height and contain
Measure the polylysine of linear epsilon-polylysine.
According to the present invention, the present invention protects the α amino of lysine using dynamic protection group, reduces α amino ginseng
The probability reacted with thermal polycondensation, to achieve the purpose that improve linear epsilon-polylysine content.The dynamic protection group should have
There is the characteristics of capable of being gradually deprotected during thermal polycondensation, operated without additional deprotection, the dynamic is protected
Shield group is to high temperature for that can form unstable amido bond, imine linkage and the dynamic protection group with the α amino of lysine
(100 DEG C or more), water, strong alkali labile blocking group, the dynamic protection group is preferably carbonyl complex, acyl group
Class compound or aldehyde radical class compound, more preferably benzyloxycarbonyl group, tertbutyloxycarbonyl, fluorenylmethyloxycarbonyl, allyloxycarbonyl, methoxy
Carbonyl, carbethoxyl group, trimethylsilyl ethoxycarbonyl, phthalyl, p-toluenesulfonyl, trifluoroacetyl group, neighbour (to) nitre
One or more of base benzenesulfonyl, pivaloyl group, benzoyl, benzaldehyde or isobutylaldehyde.
According to the present invention, L-lysine mono-hydrochloric salts and alkali are first added in the reaction vessel, then adds dynamic protection
Group or compound containing dynamic protection group are reacted, and the lysine monomer of dynamic protection radical protection is obtained；It is described
The compound containing dynamic protection group be different according to the type of dynamic protection group and substance, according to people in the art
The known carry out conventional selection of member, is not particularly limited；The compound containing dynamic protection group is preferably two carbonic acid
Di tert butyl carbonate, benzyl chloroformate or trifluoroacetic acid ethyl mercaptan ester；When dynamic protection group is aldehydes, it is anti-that progress can be directly added into
It answers, when dynamic protection group is carbonyl class or acyl group class, needs the compound containing dynamic protection group is added and be reacted,
The reaction condition is different according to the type of the dynamic protection group of addition, when dynamic protection group is carbonyl class, reaction
Temperature is preferably 0 DEG C -100 DEG C, and more preferably 25 DEG C, the reaction time is preferably 1h-24h；When dynamic protection group be acyl group class,
Reaction temperature is preferably 25 DEG C -150 DEG C, and more preferably 25 DEG C, the reaction time is preferably 3h-24h；When dynamic protection group is aldehyde
Class, reaction temperature are preferably 0 DEG C -50 DEG C, and more preferably 0 DEG C, the reaction time is preferably 1h-12h；
According to the present invention, the alkali be sodium hydroxide, potassium hydroxide, triethylamine, potassium carbonate, sodium carbonate, concentrated ammonia liquor or
It is one or more in pyridine.
According to the present invention, the molar ratio of the L-lysine mono-hydrochloric salts, alkali and dynamic protection group is preferably 1:
(0.5-2.5):(1-3)。
According to the present invention, the lysine monomer of dynamic protection radical protection obtained above and alkali are placed in mortar, ground
Mixing is ground, under the conditions of 100 DEG C -250 DEG C, catalyst is added, is stirred to react 1-72h, termination reaction is cooled to room temperature, washs,
It drains, obtains the polylysine of the linear epsilon-polylysine of high-content.The reaction temperature of the step two is 100-250 DEG C, excellent
It is selected as 150-200 DEG C, time 1-72h, preferably 20-48h；If being less than 100 DEG C, dissolubility is influenced, if being higher than 250
DEG C, product is easily crosslinked, therefore should reasonable controlling reaction temperature.
According to the present invention, the alkali in the step two is preferably lithium hydroxide, sodium hydroxide, potassium hydroxide, hydroxide
It is one or more in caesium, potassium carbonate, sodium carbonate, potassium tert-butoxide, sodium tert-butoxide.
According to the present invention, mole of the lysine monomer of dynamic protection radical protection and the alkali in the step two
Than being preferably 1:0.5-5.
According to the present invention, the catalyst in the step two has following general formula：
MLx
Wherein, M is titanium (Ti), zirconium (Zr), hafnium (Hf), scandium (Sc), yttrium (Y), cobalt (Co), nickel (Ni), palladium (Pd), antimony
(Sb), vanadium (V), niobium (Nb), tantalum (Ta), chromium (Cr), molybdenum (Mo), tungsten (W), manganese (Mn), rhenium (Re), iron (Fe), ruthenium (Ru), osmium
(Os), rhodium (Rh), iridium (Ir), golden (Au), platinum (Pt), silver-colored (Ag), copper (Cu), zinc (Zn), cadmium (Cd), boron (B), aluminium (Al), lanthanum
(La), one or more of samarium (Sm), cerium (Ce), neodymium (Nd), ytterbium (Yb)；
L is fluorine (F), chlorine (Cl), bromine (Br), iodine (I), methyl (CH3), ethyl (CH3CH2), propyl (CH3CH2CH2-)、
Isopropyl ((CH3)2CH-), butyl (CH3CH2CH2CH2), tertiary butyl ((CH3)3C-), methoxyl group (CH3O-), ethyoxyl
(CH3CH2O-), propoxyl group (CH3CH2CH2O-), isopropoxy ((CH3)2CHO-), butoxy (CH3CH2CH2CH2O-), tertiary fourth oxygen
Base ((CH3)3CO-), acetate (CH3CH2OO-), propionyloxy (CH3CH2CH2OO-), isopropyl acidic group ((CH3)2CHOO-), butyric acid
Base (CH3CH2CH2CH2One or more of OO-)；X is the integer of 1-6.More preferably zirconium-n-butylate (Zr (OC4H9)4), just
Butanol titanium (Ti (OC4H9)4), ethyoxyl antimony (Sb (OC2H5)3) aluminium isopropoxide (Al (OCH (CH3)2)3One or more of).
According to the present invention, catalyst accounts for the lysine monomer of the dynamic protection radical protection in the step two
The 0.05%-8% of molar fraction.
According to the present invention, washing is first washs with a large amount of methanol in the step two, suction filtration, removes insoluble matter, then
With a large amount of water washing, filters and remove insoluble matter.
Further detailed description done to the present invention with reference to specific embodiment, to raw material is quotient involved in embodiment
Purchase obtains.
Embodiment 1
(1), the preparation of α-benzaldehyde protection-lysine monomer
In 100mL single necked round bottom flask, 5g lysine monohydrochlorides are added, 35mL water dissolutions are added, add 1.08g hydrogen
Sodium oxide molybdena under the conditions of ice-water bath, instills 2.9mL benzaldehydes, after being added dropwise, is vigorously stirred reaction 2 hours, product precipitation analysis
Go out, filter, remove filtrate, product is washed with cold ethyl alcohol, 12 hours dry under vacuum condition, obtains white object product α-benzene first
Aldehyde protection-lysine monomer (4.78g, 75%).1H NMR(DMSO-d6,300MHz)δ1.19-1.31(m,2H),1.38(s,
2H),1.53-1.65(m,2H),1.81-2.00(m,2H),2.66-2.72(t,2H),4.19-4.25(t,2H),7.51-7.59
(m,3H),7.74-7.79(m,2H),8.67(s,1H).
(2), the preparation of High Linear epsilon-polylysine content polylysine
4.68g α-benzaldehyde protection-lysine monomer is ground with 0.8g sodium hydroxides in mortar, then by mixture
It is placed in Schlenk pipes, is heated to 150 DEG C, add 0.3mL butanol zirconiums (Zr (OBu)4), it is stirred under the conditions of being kept for 150 DEG C anti-
It answers 24 hours, is cooled to room temperature, product is dissolved in methanol, filters, and removes insoluble matter, and filtrate is spin-dried for, is washed with water, and 50 DEG C of vacuum are dry
Dry 12 hours, target product polylysine is obtained, by nmr analysis, it is 83% to obtain wherein linear epsilon-polylysine content.
Embodiment 2
(1), the preparation of α-tertbutyloxycarbonyl protection-lysine monomer
In 100mL single necked round bottom flask, 5g lysine monohydrochlorides are added, 20mL water dissolutions are added, add 1.2g hydrogen
Sodium oxide molybdena under the conditions of ice-water bath, instills the tetrahydrofuran solution 20mL containing 3.0g di-tert-butyl dicarbonates, after being added dropwise,
It is stirred to react at room temperature 24 hours, after reaction, extraction is spin-dried for, column chromatography, obtains target product α-tertbutyloxycarbonyl protection-
Lysine monomer (5.31g, 80%).1H NMR(D2O,300MHz)δ1.12(s,2H),1.22-1.31(m,2H),1.42(s,
9H),1.47-1.60(m,2H),1.73-1.86(m,2H),2.66-2.72(t,2H),4.53-4.57(t,1H),5.49(s,
1H).
(2), the preparation of High Linear epsilon-polylysine content polylysine
3.69g α-tertbutyloxycarbonyl protection-lysine monomer is ground with 0.84g potassium hydroxide in mortar, then will
Mixture is placed in Schlenk pipes, is heated to 160 DEG C, adds 0.2mL butanol titanium (Ti (OBu)4), it keeps under the conditions of 160 DEG C
It is stirred to react 20 hours, is cooled to room temperature, product is dissolved in methanol, filters, and removes insoluble matter, and filtrate is spin-dried for, is washed with water, 50 DEG C
Vacuum drying 12 hours, obtains target product polylysine, by nmr analysis, obtaining wherein linear epsilon-polylysine content is
85%.
Embodiment 3
(1), the preparation of α-benzyloxycarbonyl group protection-lysine monomer
In 100mL single necked round bottom flask, 5g lysine monohydrochlorides are added, 20mL water dissolutions are added, add 1.5g hydrogen
Potassium oxide under the conditions of ice-water bath, instills the tetrahydrofuran solution 20mL containing 5.1g benzyl chloroformates, after being added dropwise, room temperature
Under be stirred to react 24 hours, after reaction, extraction is spin-dried for, and is recrystallized, is obtained target product α-benzyloxycarbonyl group protection-lysine
Monomer (5.3g, 70%).1H NMR(D2O,300MHz)δ1.10(s,2H),1.18-1.31(m,2H),1.48-1.60(m,2H),
1.74-1.84(m,2H),2.66-2.72(t,2H),4.52-4.57(t,1H),5.05(s,2H),5.52(s,1H),7.33(s,
5H).
(2), the preparation of High Linear epsilon-polylysine content polylysine
4.2g α-benzyloxycarbonyl group protection-lysine monomer is ground with 0.36g lithium hydroxides in mortar, it then will mixing
Object is placed in Schlenk pipes, is heated to 150 DEG C, adds 2mg scandium chlorides (ScCl3), it is stirred to react under the conditions of being kept for 150 DEG C
It 30 hours, is cooled to room temperature, product is dissolved in methanol, filters, and removes insoluble matter, and filtrate is spin-dried for, is washed with water, 50 DEG C of vacuum drying
12 hours, target product polylysine is obtained, by nmr analysis, it is 82% to obtain wherein linear epsilon-polylysine content.
Embodiment 4
(1), the preparation of α-trifluoroacetyl group protection-lysine monomer
In 100mL single necked round bottom flask, 5g lysine monohydrochlorides are added, it is molten that 28mL (1M) sodium hydrate aqueous solution is added
Solution, adds 5.5mL trifluoroacetic acid ethyl mercaptan esters, is stirred to react at room temperature 10 hours, product Precipitation, filters, and removes filter
Liquid, recrystallization, obtains target product α-trifluoroacetyl group protection-lysine monomer (4.6g, 70%).1H NMR(DMSO-d6,
300MHz)δ1.13(s,2H),1.18-1.31(m,2H),1.49-1.61(m,2H),1.74-1.85(m,2H),2.66-2.72
(t,2H),4.53-4.57(t,1H),7.12(s,1H).
(2), the preparation of High Linear epsilon-polylysine content polylysine
3.6g α-trifluoroacetyl group protection-lysine monomer is ground with 0.36g lithium hydroxides in mortar, will then be mixed
It closes object to be placed in Schlenk pipes, is heated to 200 DEG C, adds 1mg triethyl aluminums (Al (CH3CH2)3), it keeps under the conditions of 200 DEG C
It is stirred to react 48 hours, is cooled to room temperature, product is dissolved in methanol, filters, and removes insoluble matter, and filtrate is spin-dried for, is washed with water, 50 DEG C
Vacuum drying 12 hours, obtains target product polylysine, by nmr analysis, obtaining wherein linear epsilon-polylysine content is
85%.
Embodiment 5
(1), the preparation of α-isobutylaldehyde protection-lysine monomer
In 100mL single necked round bottom flask, 5g lysine monohydrochlorides are added, 35mL water dissolutions are added, add 1.08g hydrogen
Sodium oxide molybdena under the conditions of ice-water bath, instills 2.5mL isobutylaldehydes, after being added dropwise, is vigorously stirred reaction 3 hours, product precipitation analysis
Go out, filter, remove filtrate, product is washed with cold ethyl alcohol, 12 hours dry under vacuum condition, obtains white object product α-isobutyl
Aldehyde protection-lysine monomer (3.5g, 65%).1H NMR(DMSO-d6,300MHz)δ0.83-0.85(d,6H),1.19-1.30
(m,4H),1.41-1.49(m,1H),1.56-1.71(m,3H),2.65-2.78(m,3H),4.24-4.30(t,1H),7.67-
7.70(d,1H).
(2), the preparation of High Linear epsilon-polylysine content polylysine
3.0g α-isobutylaldehyde protection-lysine monomer is ground with 0.6g sodium hydroxides in mortar, then by mixture
It is placed in Schlenk pipes, is heated to 150 DEG C, add 0.2mL butanol zirconiums (Zr (OBu)4), it is stirred under the conditions of being kept for 150 DEG C anti-
It answers 24 hours, is cooled to room temperature, product is dissolved in methanol, filters, and removes insoluble matter, and filtrate is spin-dried for, is washed with water, and 50 DEG C of vacuum are dry
Dry 12 hours, target product polylysine is obtained, by nmr analysis, it is 83% to obtain wherein linear epsilon-polylysine content.
Embodiment 6
(1), the preparation of α-tertbutyloxycarbonyl protection-lysine monomer
In 100mL single necked round bottom flask, 5g lysine monohydrochlorides are added, 20mL water dissolutions are added, add 1.2g hydrogen
Sodium oxide molybdena under the conditions of ice-water bath, instills the tetrahydrofuran solution 20mL containing 3.0g di-tert-butyl dicarbonates, after being added dropwise,
It is stirred to react at room temperature 24 hours, after reaction, extraction is spin-dried for, column chromatography, obtains target product α-tertbutyloxycarbonyl protection-
Lysine monomer (5.31g, 80%).1H NMR(D2O,300MHz)δ1.12(s,2H),1.22-1.31(m,2H),1.42(s,
9H),1.47-1.60(m,2H),1.73-1.86(m,2H),2.66-2.72(t,2H),4.53-4.57(t,1H),5.49(s,
1H).
(2), the preparation of High Linear epsilon-polylysine content polylysine
3.69g α-tertbutyloxycarbonyl protection-lysine monomer is ground with 2.07g potassium carbonate in mortar, will then be mixed
It closes object to be placed in Schlenk pipes, is heated to 160 DEG C, adds 11mg ethyl alcohol antimony (Sb (OEt)3), it is stirred under the conditions of being kept for 160 DEG C
Reaction 30 hours is mixed, is cooled to room temperature, product is dissolved in methanol, filters, and removes insoluble matter, and filtrate is spin-dried for, is washed with water, and 50 DEG C true
Sky is 12 hours dry, obtains target product polylysine, by nmr analysis, obtaining wherein linear epsilon-polylysine content is
85%.
Dynamic protection group used in above-described embodiment can also be fluorenylmethyloxycarbonyl, allyloxycarbonyl, methoxy carbonyl
Base, carbethoxyl group, trimethylsilyl ethoxycarbonyl, phthalyl, p-toluenesulfonyl, neighbour (to) nitrobenzenesulfonyl, spy
One or more of valeryl, benzoyl.Used alkali can also be in sodium carbonate, potassium tert-butoxide, sodium tert-butoxide
It is one or more.Used catalyst can also be hafnium (Hf), scandium (Sc), yttrium (Y), cobalt (Co), nickel (Ni), palladium (Pd), vanadium
(V), niobium (Nb), tantalum (Ta), chromium (Cr), molybdenum (Mo), tungsten (W), manganese (Mn), rhenium (Re), iron (Fe), ruthenium (Ru), osmium (Os), rhodium
(Rh), iridium (Ir), golden (Au), platinum (Pt), silver-colored (Ag), copper (Cu), zinc (Zn), cadmium (Cd), boron (B), aluminium (Al), lanthanum (La), samarium
(Sm), one or more of the halide of the metals such as cerium (Ce), neodymium (Nd), ytterbium (Yb) and its organo-metallic compound.Here
It will not enumerate example.
Claims (10)
1. a kind of method that thermal polycondensation prepares the polylysine of the linear epsilon-polylysine of high-content, which is characterized in that this method packet
It includes：
Step 1：The α amino of lysine is protected using dynamic protection group, obtains relying for dynamic protection radical protection
Propylhomoserin monomer；
The dynamic protection group is the protecting group that unstable amido bond, imine linkage can be formed with the α amino of lysine
Group；
Step 2：The lysine monomer for the dynamic protection radical protection that step 1 obtains is ground with alkali, at 100 DEG C -250
Under the conditions of DEG C, catalyst is added, is stirred to react 1-72h, be cooled to room temperature termination reaction, washing drains, it is linear to obtain high-content
The polylysine of epsilon-polylysine.
2. the method that a kind of thermal polycondensation according to claim 1 prepares the polylysine of the linear epsilon-polylysine of high-content,
It is characterized in that, the dynamic protection group is selected from benzyloxycarbonyl group, tertbutyloxycarbonyl, fluorenylmethyloxycarbonyl, allyloxycarbonyl, first
Oxygen carbonyl, carbethoxyl group, trimethylsilyl ethoxycarbonyl, phthalyl, p-toluenesulfonyl, trifluoroacetyl group, neighbour's (to)
One or more of nitrobenzenesulfonyl, pivaloyl group, benzoyl, benzaldehyde or isobutylaldehyde.
3. the method that a kind of thermal polycondensation according to claim 1 prepares the polylysine of the linear epsilon-polylysine of high-content,
The step one is specially：L-lysine mono-hydrochloric salts and alkali are added in the reaction vessel, then adds dynamic protection base
Group or the compound containing dynamic protection group are reacted, and the lysine monomer of dynamic protection radical protection is obtained.
4. the method that a kind of thermal polycondensation according to claim 3 prepares the polylysine of the linear epsilon-polylysine of high-content,
The reaction temperature of the step one is 0 DEG C -150 DEG C, reaction time 1h-24h.
5. the method that a kind of thermal polycondensation according to claim 3 prepares the polylysine of the linear epsilon-polylysine of high-content,
The alkali is one or more in sodium hydroxide, potassium hydroxide, triethylamine, potassium carbonate, sodium carbonate, concentrated ammonia liquor or pyridine.
6. the method that a kind of thermal polycondensation according to claim 1 prepares the polylysine of the linear epsilon-polylysine of high-content,
Alkali in the step two is lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, potassium carbonate, sodium carbonate, the tert-butyl alcohol
It is one or more in potassium or sodium tert-butoxide.
7. the method that a kind of thermal polycondensation according to claim 1 prepares the polylysine of the linear epsilon-polylysine of high-content,
The molar ratio of the lysine monomer of dynamic protection radical protection and the alkali is 1 in the step two:(0.5-5).
8. the method that a kind of thermal polycondensation according to claim 1 prepares the polylysine of the linear epsilon-polylysine of high-content,
Catalyst in the step two has following general formula：
MLx
Wherein, M be titanium, zirconium, hafnium, scandium, yttrium, cobalt, nickel, palladium, antimony, vanadium, niobium, tantalum, chromium, molybdenum, tungsten, manganese, rhenium, iron, ruthenium, osmium, rhodium,
One or more of iridium, gold, platinum, silver, copper, zinc, cadmium, boron, aluminium, lanthanum, samarium, cerium, neodymium or ytterbium；
L is fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, methoxyl group, ethyoxyl, propoxyl group, different
One or more of propoxyl group, butoxy, tert-butoxy, acetate, propionyloxy, isopropyl acidic group or butyric acid base；X is 1-6's
Integer.
9. the method that a kind of thermal polycondensation according to claim 1 prepares the polylysine of the linear epsilon-polylysine of high-content,
Catalyst accounts for the 0.05%- of the molar fraction of the lysine monomer of the dynamic protection radical protection in the step two
8%.
10. the method that a kind of thermal polycondensation according to claim 1 prepares the polylysine of the linear epsilon-polylysine of high-content,
Washing in the step two is first to be washed with methanol, is filtered, and removes insoluble matter, is washed with water and washs, and filters and removes insoluble matter.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113861231A (en) * | 2021-11-11 | 2021-12-31 | 中国科学院长春应用化学研究所 | Amino acid modification-based bionic rubber and application thereof in preparation of aircraft tire tread rubber |
| CN114621431A (en) * | 2022-01-20 | 2022-06-14 | 浙江大学 | Hyperbranched polylysine powder with low polydispersity index and method for the production thereof |
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| CN103917623A (en) * | 2011-07-28 | 2014-07-09 | 巴斯夫欧洲公司 | Use of hyperbranched polylysine as shale inhibitor |
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| CN114621431A (en) * | 2022-01-20 | 2022-06-14 | 浙江大学 | Hyperbranched polylysine powder with low polydispersity index and method for the production thereof |
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