CN107602662A - A kind of preparation method of fragrant hydrazides macrocyclic compounds - Google Patents
A kind of preparation method of fragrant hydrazides macrocyclic compounds Download PDFInfo
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- CN107602662A CN107602662A CN201710707681.9A CN201710707681A CN107602662A CN 107602662 A CN107602662 A CN 107602662A CN 201710707681 A CN201710707681 A CN 201710707681A CN 107602662 A CN107602662 A CN 107602662A
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- 0 CC*c(cc(**)c(C(*(*)*)=O)c1)c1C(*(*(C(c1cc(C(*I)=*)ccc1)=N)I)I)=O Chemical compound CC*c(cc(**)c(C(*(*)*)=O)c1)c1C(*(*(C(c1cc(C(*I)=*)ccc1)=N)I)I)=O 0.000 description 2
- MLZRUSKIYQALJC-UHFFFAOYSA-N CC(c1cccc(C=O)c1)=C Chemical compound CC(c1cccc(C=O)c1)=C MLZRUSKIYQALJC-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a kind of preparation method of fragrant hydrazides macrocyclic compounds, belong to the synthesis technical field of organic functional material.Technical scheme main points are：
Description
Technical field
The invention belongs to the synthesis technical field of organic functional material, and in particular to a kind of fragrant hydrazides macrocyclic compounds
Preparation method.
Background technology
Compared with ol cpds, macrocyclic compound has the structure of closed hoop, and it is unique that this design feature assigns it
Property and function, therefore macrocyclic compound is all widely used in biological medicine, functional material etc..According to big ring point
The pliability of subring skeleton, macrocycle molecule can be divided into flexible big ring and rigid macrocyclic.The Typical Representative of flexible big ring is crown ether
Class compound, this kind of compound occupy critical role in the structure of molecule, ion identification and functional molecular.Rigid macrocyclic by
It is relatively fixed in its conformation, and it is most of with stronger pi-pi accumulation effect and hydrophobic effect, easily by self assembly
Form the assembly with higher structure, such as porphyrin macrocyclic compound, benzyne class macrocyclic compound etc..It is various on plane of a loop
Functional group, impart the diversity of big ring supermolecule aggregation.If big ring passes through functional group and specific company with export-oriented functional group
The effect of node, a variety of supramolecular structures can be formed；If with interior to functional group, big ring can be used as host compound in chi
The guest compound being mutually matched in terms of very little, polarity and functional group is identified.Therefore, macrocycle molecule has many special property
Can, in nonlinear optics, photoelectric functional material, separation material, Organic Ferromagnet, ferroelectric, liquid crystal and host-guest chemistry etc.
Field has important and is widely applied.With the extensive blending in each field, functional big ring more and more attracts attention.
Aromatic hydrazide kind macrocyclic compound be by several fragrant hydrazyde units intramolecular hydrogen bond effect under, connected by hydrazides key
Connect the compound with cyclic conformation to be formed.Often there is higher structural stability, and such macrocyclic compound root
It can be formed from several according to the difference of construction unitThe interior cave to be differed in size to 1-2nm.There is big pi-conjugated system to this kind of
The research of rigid annular compound is very active in recent years.Due to this kind of macrocyclic compound skeleton in rigidity, construction unit it
Between the conformational freedom that rotates it is very limited, thus produce very big molecular surface, acted on by the pi-pi accumulation of plane of a loop etc.,
Different types of nano molecular structure, such as nanotube, line and vesica can be self-assembly of, in drug delivery and is sustained, artificial
Ion channel, liquid crystal etc. show the property of uniqueness.
The method for synthesizing fragrant hydrazides macrocyclic compounds at present has：It is the intramolecular cyclization of the oligomer containing difunctional, multiple
The methods of intermolecular cyclization of oligomer and the cyclization using template reaction.First two method is advantageous to the big of accurate control ring
It is small, and the functional groups on phenyl ring are not influenceed, so it is relatively the most frequently used, but its shortcoming is the precursor oligomerization of cyclization
Thing synthesis such as is related to protecting, be coupled and deprotect at multiple repetitive processes, and annulation is generally required in low consistency conditions
Lower progress, so as to cause synthesis very cumbersome and time-consuming, and yield is still very low.It is special that the cyclization method of template reaction needs to have
The substrate of functional group, can be non-covalent for the angle of synthesis by the design of template come the size of control ring as template
Easily connection and the removal of the template of key, so as to which effect is more preferable, but template reaction is also required to carry out under conditions of low concentration, and
And suitable template must be selected to be connected and removed, increase extra synthesis step.
In summary, at present fragrant hydrazides macrocyclic compounds preparation method step it is tediously long, can efficiently prepare manually across
The method of film is rarely reported.
The content of the invention
Present invention solves the technical problem that it there is provided a kind of short synthetic route, high income and workable fragrant hydrazides
The preparation method of macrocyclic compounds.
The present invention is to solve above-mentioned technical problem to adopt the following technical scheme that, a kind of preparation of fragrant hydrazides macrocyclic compounds
Method, it is characterised in that concretely comprise the following steps：
(1) by 4,6- dihydroxy M-phthalic acids methyl esters 1, phenylalanine tripeptides 2 and alkali in reaction dissolvent it is anti-in 60 DEG C
4, the 6- dihydroxy M-phthalic acids methyl esters 3 of double phenylalanine tripeptides modifications should be made, wherein alkali is potassium carbonate, cesium carbonate, hydrogen
It is acetonitrile, acetone or DMF to change sodium, sodium carbonate, sodium hydroxide or potassium hydroxide, reaction dissolvent；
(2) by the 4,6- dihydroxy M-phthalic acids methyl esters 3 of double phenylalanine tripeptides modification and hydrazine hydrate in reaction dissolvent
In 4, the 6- dihydroxy isopthalic dihydrazides 4 of double phenylalanine tripeptides modifications is made in 50 DEG C of reactions, wherein reaction dissolvent is second
Alcohol, tetrahydrofuran, ethanol/tetrahydrofuran mixed solvent or methanol/tetrahydrofuran mixed solvent；
(3) 4,6- dihydroxy isopthalic dihydrazide 4, alkali and the m-phthaloyl chloride class for modifying double phenylalanine tripeptides
Target product virtue hydrazides macrocyclic compounds 6 are made in the back flow reaction in reaction dissolvent of compound 5, and wherein alkali is 4- dimethylamino pyrroles
Pyridine, triethylamine or pyridine, reaction dissolvent are dichloromethane, DMF or DMA；
Specifically synthetic route is：
Further preferably, the specific building-up process of step (1) is：By 4,6- dihydroxy M-phthalic acids methyl esters 1, phenylpropyl alcohol ammonia
Sour tripeptides 2 and potassium carbonate are added in three-necked bottle, are added acetonitrile dissolving, are connected reflux condensing tube on three-necked bottle, on condenser pipe
Three passband balloons are connect, moves into 60 DEG C of oil baths and reacts after displacement nitrogen, after TLC monitoring reactions terminate, stops heating, is spin-dried for solvent
Extracted using water/dichloromethane system, merge organic phase, be spin-dried for after anhydrous sodium sulfate drying, column chromatography obtains double phenylpropyl alcohol ammonia
The 4,6- dihydroxy M-phthalic acids methyl esters 3 of sour tripeptides modification.
Further preferably, 4,6- dihydroxy M-phthalic acids methyl esters described in step (1) 1, phenylalanine tripeptides 2 and carbonic acid
The molar ratio of potassium is 1:3:6.
Further preferably, the specific building-up process of step (2) is：By between the 4,6- dihydroxy of double phenylalanine tripeptides modification
Phthalic acid methyl ester 3 is dissolved in ethanol/tetrahydrofuran in the mixed solvent, adds hydrazine hydrate rear substitution nitrogen, is placed in 50 DEG C of oil bath
Middle reaction 24 hours, White Flocculus generation is carried out with reaction, after the completion of TLC monitoring reactions, oil bath has been removed and stands, mistake
Filter obtains the 4,6- dihydroxy isopthalic dihydrazide 4 of double phenylalanine tripeptides modifications.
Further preferably, 4, the 6- dihydroxy M-phthalic acids methyl esters 3 of double phenylalanine tripeptides modifications described in step (2)
With N2H2·H2O molar ratio is 1:20.
Further preferably, the specific building-up process of step (3) is：By between the 4,6- dihydroxy of double phenylalanine tripeptides modification
Phenyl-diformyl hydrazine 4 is added in round-bottomed flask, adds DMAP, and addition anhydrous methylene chloride is molten after replacing nitrogen
Solution, and stirred in ice salt bath, 4,6- dihydroxy isopthalic dihydrazide 4 and m-phthaloyl chloride class compound 5 are pressed into equimolar
Amount is added in round-bottomed flask, ice salt bath is maintained after addition 2 hours, after question response system is back to room temperature naturally, moves into oil
Back flow reaction 24 hours in bath, reaction are spin-dried for solvent after terminating, and solid residue is redissolved in dichloromethane, and uses watery hydrochloric acid
Wash, wash, finally washed with saturated common salt, gained organic phase is spin-dried for after anhydrous sodium sulfate drying, and column chromatography obtains target production
Thing virtue hydrazides macrocyclic compounds 6.
Further preferably, 4, the 6- dihydroxy isopthalic dihydrazide 4 of double phenylalanine tripeptides modifications described in step (3) with
The molar ratio of DMAP is 1:2.
The present invention has the advantages that relative to traditional synthetic method：
1st, one is passed through as raw material using the 4,6- dihydroxy M-phthalic acid methyl esters of double phenylalanine tripeptides modification in the present invention
4, the 6- dihydroxy isopthalic dihydrazides of the double phenylalanine tripeptides modifications of step reaction generation, with ethanol/tetrahydrofuran mixed solvent
For reaction dissolvent, 4, the 6- dihydroxy isopthalic dihydrazide Direct precipitations of double phenylalanine tripeptides modification of course of reaction generation go out
Come, reaction can directly obtain double phenylalanine tripeptides modifications by filtering 4,6- dihydroxy isopthalic dihydrazides after terminating are pure
Product, the step of isolating and purifying is eliminated, saved cost while simplified experimental implementation；
2nd, the 4,6- dihydroxy isopthalic dihydrazide and m-phthaloyl chloride for modifying double phenylalanine tripeptides in the present invention
Class compound feeds intake by equimolar amounts, under the promotion of intermolecular hydrogen bonding and intramolecular hydrogen bond, reacts direct by one step to form the loop
Fragrant hydrazides macrocyclic compounds have been synthesized, have simplified the intramolecular cyclization of traditional oligomer containing difunctional, multiple oligomers
Synthetic reaction step in the ring closure reaction of intermolecular cyclization and utilization template reaction, improve the yield of target product.
Embodiment
The above of the present invention is described in further details by the following examples, but this should not be interpreted as to this
The scope for inventing above-mentioned theme is only limitted to following embodiment, and all technologies realized based on the above of the present invention belong to this hair
Bright scope.
Embodiment 1
The preparation of the 4,6- dihydroxy M-phthalic acid methyl esters of double phenylalanine tripeptides modifications
Weigh 4,6- dihydroxy M-phthalic acid methyl esters (0.68g, 3.0mmol), phenylalanine tripeptides (5.33g,
9.0mmol) it is added to potassium carbonate (2.49g, 18mmol) in three-necked bottle, adds acetonitrile 100mL dissolvings, connected on three-necked bottle
Reflux condensing tube, threeway (band balloon) is connect on condenser pipe, replace to move into 60 DEG C of oil baths after nitrogen and react.TLC monitoring reaction knots
Shu Hou, stop heating, be spin-dried for solvent, extracted using water/DCM systems, merge organic phase, be spin-dried for after anhydrous sodium sulfate drying,
Column chromatography obtains 4, the 6- dihydroxy M-phthalic acid methyl esters of the double phenylalanine tripeptides modifications of white solid, yield 95%.
1H NMR(400MHz,CDCl3):δ 8.69 (s, 1H), 8.43 (d, J=8Hz, 2H), 7.24-6.99 (m, 30H),
6.86 (s, 1H), 6.60 (d, J=8Hz, 1H), 6.37 (s, 1H), 6.31 (d, J=8Hz, 2H), 4.8 (m, 2H), 4.66-4.58
(m, 4H), 4.36 (m, 4H), 3.95 (s, 6H), 3.21 (d, J=4Hz, 1H), 3.18 (d, J=4Hz, 1H), 3.10-2.92 (m,
10H),1.34(s,18H).HR-MS(ESI-TOF):Calcd.For C76H84N6O16Na[M+Na]+:1359.5842.Found:
1359.5836。
Embodiment 2
The preparation of the 4,6- dihydroxy isopthalic dihydrazides of double phenylalanine tripeptides modifications
The 4,6- dihydroxy M-phthalic acid methyl esters (1.34g, 1.0mmol) for weighing double phenylalanine tripeptides modifications is dissolved in second
Alcohol/tetrahydrofuran in the mixed solvent, hydrazine hydrate (85%, 9.7mL, 20mmol) rear substitution nitrogen is added, is placed in 50 DEG C of oil baths
Reaction 24 hours.White Flocculus generation has been carried out with reaction, after the completion of TLC monitoring reactions, oil bath has been removed and stands, filtering
Obtain 4, the 6- dihydroxy isopthalic dihydrazides of double phenylalanine tripeptides modifications, yield 45%.
1H NMR(400MHz,DMSO-d6):δ 9.61 (s, 2H), 8.52-8.48 (m, 4H), 8.32 (d, J=8Hz, 2H),
8.16(s,1H),7.28-7.03(m,30H),6.26(s,1H),4.61-4.56(m,6H),4.42-4.37(m,8H),3.04-
2.96(m,8H),2.82-2.65(m,4H),1.30(s,18H).HR-MS(ESI-TOF):Calcd.For C74H85N10O14[M+
H]+:1337.6247.Found:1337.6229。
Embodiment 3
The preparation of fragrant hydrazides macrocyclic compound
50mL tool branch flasks are taken out from drying box, seals and does anhydrous and oxygen-free processing, add malonic acid diacid chloride
After (0.10g, 0.50mmol) displacement nitrogen, anhydrous methylene chloride 20mL dissolvings are added, then add DMAP
(122mg, 1.0mmol), and stirred in ice salt bath.Then take the 4,6- dihydroxy isophthalic diformazans of double phenylalanine tripeptides modifications
Hydrazides (0.12g, 0.50mmol) is added in reaction system, ice salt bath is maintained after addition 2 hours.Question response system is returned naturally
To room temperature, back flow reaction 24 hours in oil bath are moved into.After reaction terminates, after being spin-dried for solvent, solid residue is redissolved in dichloro
In methane (50mL), and (0.5M, 50mL), washing (50mL) are washed with watery hydrochloric acid, finally washed (50mL) with saturated common salt.Gained
Organic phase is spin-dried for after anhydrous sodium sulfate drying, and column chromatography obtains target product virtue hydrazides macrocyclic compound, yield 69%.
1H NMR(400MHz,DMSO-d6):δ10.80(s,5H),10.38(s,5H),8.55-8.14(m,29H),7.66-
7.64(m,3H),7.22-7.07(m,93H),6.25(br,3H),4.65-4.33(m,30H),3.02-2.94(m,24H),
2.75-2.67(m,12H),1.27(s,54H).HRMS:Calcd for C246H258N30Na2O48[M+Na]2+:
2223.9266.Found:2223.9249。
Embodiment 4
The preparation of methoxyl group virtue hydrazides macrocyclic compound
50mL tool branch flasks are taken out from drying box, seals and does anhydrous and oxygen-free processing, add the different isophathalic acid of 2- methoxyl groups
After diacid chloride (0.12g, 0.50mmol) displacement nitrogen, anhydrous methylene chloride 20mL dissolvings are added, then add 4- dimethylaminos
Pyridine (122mg, 1.0mmol), and stirred in ice salt bath.Then take the 4,6- dihydroxy isophthalic of double phenylalanine tripeptides modifications
Diformylhydrazine (0.12g, 0.50mmol) is added in reaction system, ice salt bath is maintained after addition 2 hours.Question response system is certainly
After being so back to room temperature, back flow reaction 24 hours in oil bath are moved into.After reaction terminates, after being spin-dried for solvent, solid residue is redissolved in
In dichloromethane (50mL), and (0.5M, 50mL), washing (50mL) are washed with watery hydrochloric acid, finally washed (50mL) with saturated common salt.
Gained organic phase is spin-dried for after anhydrous sodium sulfate drying, and column chromatography obtains target product virtue hydrazides macrocyclic compound, yield 63%.
1H NMR(400MHz,DMSO-d6):δ10.45-10.39(m,10H),8.51-8.33(m,20H),7.74-7.70
(m,6H),7.22-7.07(m,96H),6.33-6.29(m,3H),4.68-4.34(m,30H),4.01(s,6H),3.9(s,
3H),3.04-2.96(m,24H),2.80-2.67(m,12H),1.28(s,54H).HRMS:Calcd for
C249H264N30Na2O51[M+Na]2+:2268.9425.Found:2268.9414。
Embodiment 5
The preparation of diethyl malonate virtue hydrazides macrocyclic compound
50mL tool branch flasks are taken out from drying box, seals and does anhydrous and oxygen-free processing, add diethyl malonate modification
M-phthaloyl chloride (0.2g, 0.50mmol) displacement nitrogen after, add anhydrous methylene chloride 20mL dissolving, then add 4- bis-
Methylamino pyridine (122mg, 1.0mmol), and stirred in ice salt bath.Then take the 4,6- dihydroxies of double phenylalanine tripeptides modifications
Base isopthalic dihydrazide (0.12g, 0.50mmol) is added in reaction system, ice salt bath is maintained after addition 2 hours.Question response
After system is back to room temperature naturally, back flow reaction 24 hours in oil bath are moved into.After reaction terminates, after being spin-dried for solvent, solid residue weight
Newly it is dissolved in dichloromethane (50mL), and (0.5M, 50mL), washing (50mL) is washed with watery hydrochloric acid, is finally washed with saturated common salt
(50mL).Gained organic phase is spin-dried for after anhydrous sodium sulfate drying, and column chromatography obtains target product virtue hydrazides macrocyclic compound, yield
57%.
1H NMR(400MHz,DMSO-d6):δ10.70-10.30(m,10H),8.56-8.37(m,20H),7.83(br,
6H),7.23-7.08(m,96H),6.29-6.14(m,3H),5.86-5.79(m,3H),4.67-4.11(m,42H),3.11-
2.97 (m, 24H), 2.78-2.67 (m, 12H), 1.29 (s, 54H), 1.17 (t, J=6Hz, 18H) .HRMS:calcd for
C267H290N30O63[M+2H]2+2463.0239,found 2463.0271。
Embodiment 6
Cbz protects the preparation of ethamine virtue hydrazides macrocyclic compound
50mL tool branch flasks are taken out from drying box, seals and does anhydrous and oxygen-free processing, add diethyl malonate modification
M-phthaloyl chloride (0.22g, 0.50mmol) displacement nitrogen after, add anhydrous methylene chloride 20mL dissolving, then add 4-
Dimethylamino naphthyridine (122mg, 1.0mmol), and stirred in ice salt bath.Then take the 4,6- bis- of double phenylalanine tripeptides modifications
Hydroxyl isopthalic dihydrazide (0.12g, 0.50mmol) is added in reaction system, ice salt bath is maintained after addition 2 hours.Treat anti-
After answering system to be back to room temperature naturally, back flow reaction 24 hours in oil bath are moved into.After reaction terminates, after being spin-dried for solvent, solid residue
It is redissolved in dichloromethane (50mL), and (0.5M, 50mL), washing (50mL) is washed with watery hydrochloric acid, finally uses saturated aqueous common salt
Wash (50mL).Gained organic phase is spin-dried for after anhydrous sodium sulfate drying, and column chromatography obtains target product virtue hydrazides macrocyclic compound, is received
Rate 45%.
1H NMR(400MHz,DMSO-d6):δ10.56-10.37(m,10H),8.48-8.27(m,20H),7.85-7.73
(m,6H),7.24-7.07(m,114H),6.38-6.23(m,3H),5.02-4.89(m,6H),4.62-4.14(m,36H),
3.44(br,6H),3.07-2.94(m,24H),2.78-2.67(m,12H),1.30(s,54H).HRMS:HRMS:calcd for
C276H299N35O57[M+2NH4]2+2508.5821,found 2508.5823。
Embodiment above describes the general principle of the present invention, main features and advantages, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification
Reason, under the scope for not departing from the principle of the invention, various changes and modifications of the present invention are possible, and these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (7)
1. a kind of preparation method of fragrant hydrazides macrocyclic compounds, it is characterised in that concretely comprise the following steps：
(1) 4,6- dihydroxy M-phthalic acids methyl esters 1, phenylalanine tripeptides 2 and alkali are made in reaction dissolvent in 60 DEG C of reactions
Double phenylalanine tripeptides modifications 4,6- dihydroxy M-phthalic acids methyl esters 3, wherein alkali be potassium carbonate, cesium carbonate, sodium hydride,
Sodium carbonate, sodium hydroxide or potassium hydroxide, reaction dissolvent are acetonitrile, acetone or DMF；
(2) by double phenylalanine tripeptides modification 4,6- dihydroxy M-phthalic acids methyl esters 3 and hydrazine hydrate in reaction dissolvent in
4, the 6- dihydroxy isopthalic dihydrazide 4 of double phenylalanine tripeptides modifications is made in 50 DEG C of reactions, and wherein reaction dissolvent is ethanol, four
Hydrogen furans, ethanol/tetrahydrofuran mixed solvent or methanol/tetrahydrofuran mixed solvent；
(3) 4,6- dihydroxy isopthalic dihydrazide 4, alkali and the m-phthaloyl chloride class compound for modifying double phenylalanine tripeptides
5 in reaction dissolvent back flow reaction be made target product virtue hydrazides macrocyclic compounds 6, wherein alkali be DMAP,
Triethylamine or pyridine, reaction dissolvent are dichloromethane, DMF or DMA；
Specifically synthetic route is：
2. the preparation method of fragrant hydrazides macrocyclic compounds according to claim 1, it is characterised in that：The tool of step (1)
Body building-up process is：4,6- dihydroxy M-phthalic acids methyl esters 1, phenylalanine tripeptides 2 and potassium carbonate are added in three-necked bottle,
Acetonitrile dissolving is added, reflux condensing tube is connected on three-necked bottle, three passband balloons are connect on condenser pipe, 60 DEG C are moved into after replacing nitrogen
Reacted in oil bath, after TLC monitoring reactions terminate, stop heating, be spin-dried for solvent and extracted using water/dichloromethane system, is associated with
Machine phase, is spin-dried for after anhydrous sodium sulfate drying, and column chromatography obtains 4, the 6- dihydroxy isophthalic diformazans of double phenylalanine tripeptides modifications
Sour methyl esters 3.
3. the preparation method of fragrant hydrazides macrocyclic compounds according to claim 1 or 2, it is characterised in that：In step (1)
The molar ratio of the 4,6- dihydroxy M-phthalic acid methyl esters 1, phenylalanine tripeptides 2 and potassium carbonate is 1:3:6.
4. the preparation method of fragrant hydrazides macrocyclic compounds according to claim 1, it is characterised in that：The tool of step (2)
Body building-up process is：The 4,6- dihydroxy M-phthalic acids methyl esters 3 that double phenylalanine tripeptides are modified is dissolved in ethanol/tetrahydrofuran
In the mixed solvent, add hydrazine hydrate rear substitution nitrogen, be placed in 50 DEG C of oil bath and react 24 hours, with reaction carried out it is white
Color floccule produces, and after the completion of TLC monitoring reactions, removes oil bath and stands, and is filtrated to get the 4,6- of double phenylalanine tripeptides modifications
Dihydroxy isopthalic dihydrazide 4.
5. the preparation method of the fragrant hydrazides macrocyclic compounds according to claim 1 or 4, it is characterised in that：In step (2)
The 4,6- dihydroxy M-phthalic acids methyl esters 3 and N of double phenylalanine tripeptides modifications2H2·H2O molar ratio is 1:
20。
6. the preparation method of fragrant hydrazides macrocyclic compounds according to claim 1, it is characterised in that：The tool of step (3)
Body building-up process is：4, the 6- dihydroxy isopthalic dihydrazide 4 of double phenylalanine tripeptides modification is added in round-bottomed flask, then added
Enter DMAP, anhydrous methylene chloride dissolving is added after replacing nitrogen, and stirred in ice salt bath, by 4,6- dihydroxy
Isopthalic dihydrazide 4 and m-phthaloyl chloride class compound 5 are added in round-bottomed flask by equimolar amounts, are maintained after addition
Ice salt bath 2 hours, after question response system is back to room temperature naturally, back flow reaction 24 hours in oil bath are moved into, reaction is spin-dried for after terminating
Solvent, solid residue are redissolved in dichloromethane, and are washed, washed with watery hydrochloric acid, are finally washed with saturated common salt, gained is organic
Mutually it is spin-dried for after anhydrous sodium sulfate drying, column chromatography obtains target product virtue hydrazides macrocyclic compounds 6.
7. the preparation method of the fragrant hydrazides macrocyclic compounds according to claim 1 or 6, it is characterised in that：In step (3)
The molar ratio of the 4,6- dihydroxy isopthalic dihydrazide 4 and DMAP of the double phenylalanine tripeptides modification is
1:2。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103087054A (en) * | 2013-02-27 | 2013-05-08 | 山东大学 | 4-pyridyl phenyl ether compounds, and preparation method and application thereof |
| CN105732468A (en) * | 2016-04-07 | 2016-07-06 | 昆明理工大学 | N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound and preparation method and application thereof |
| CN106389419A (en) * | 2016-08-31 | 2017-02-15 | 段占娥 | Application of arylhydrazide compound in treatment of acute myocardial ischemic coronary heart disease |
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- 2017-08-17 CN CN201710707681.9A patent/CN107602662A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103087054A (en) * | 2013-02-27 | 2013-05-08 | 山东大学 | 4-pyridyl phenyl ether compounds, and preparation method and application thereof |
| CN105732468A (en) * | 2016-04-07 | 2016-07-06 | 昆明理工大学 | N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound and preparation method and application thereof |
| CN106389419A (en) * | 2016-08-31 | 2017-02-15 | 段占娥 | Application of arylhydrazide compound in treatment of acute myocardial ischemic coronary heart disease |
Non-Patent Citations (1)
| Title |
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| 这个地球不太稳: "芳香酰肼折叠体聚合物的构建及其跨膜输送研究http://www.doc88.com/p-6127754193345.html", 《道客巴巴》 * |
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