CN108727227A - Polyethers urea bridging chiral molecular tweezer and its preparation and application - Google Patents
Polyethers urea bridging chiral molecular tweezer and its preparation and application Download PDFInfo
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- CN108727227A CN108727227A CN201810622205.1A CN201810622205A CN108727227A CN 108727227 A CN108727227 A CN 108727227A CN 201810622205 A CN201810622205 A CN 201810622205A CN 108727227 A CN108727227 A CN 108727227A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 229920000570 polyether Polymers 0.000 title claims abstract description 15
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 239000004202 carbamide Substances 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 104
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
- 238000006243 chemical reaction Methods 0.000 claims description 43
- -1 methyl ester salt Chemical class 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 4
- 238000005557 chiral recognition Methods 0.000 abstract description 10
- 238000000926 separation method Methods 0.000 abstract description 6
- 239000000243 solution Substances 0.000 description 44
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical class OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 9
- 230000006837 decompression Effects 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 6
- 229930182832 D-phenylalanine Natural products 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- SWVMLNPDTIFDDY-FVGYRXGTSA-N methyl (2s)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=CC=C1 SWVMLNPDTIFDDY-FVGYRXGTSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 229960005190 phenylalanine Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- STVVMTBJNDTZBF-SECBINFHSA-N (2r)-2-amino-3-phenylpropan-1-ol Chemical class OC[C@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-SECBINFHSA-N 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 239000004383 Steviol glycoside Substances 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- YCKKQNLYSGRKQV-KCKAIOALSA-N ent-beyerane Chemical compound C1CC2C(C)(C)CCC[C@@]2(C)C(CC2)C11CCC2(C)C1 YCKKQNLYSGRKQV-KCKAIOALSA-N 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 238000012805 post-processing Methods 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 229930182488 steviol glycoside Natural products 0.000 description 3
- 235000019411 steviol glycoside Nutrition 0.000 description 3
- 150000008144 steviol glycosides Chemical class 0.000 description 3
- 235000019202 steviosides Nutrition 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical class ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001335 aliphatic alkanes Chemical group 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- 229930004069 diterpene Natural products 0.000 description 2
- 150000004141 diterpene derivatives Chemical class 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FZXAAJAZYIPUGV-JLCFLTIHSA-N (1R,2R)-cyclohexane-1,2-diamine (1S,2S)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N.N[C@@H]1CCCC[C@H]1N FZXAAJAZYIPUGV-JLCFLTIHSA-N 0.000 description 1
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- IDIHFYDGUBHGMP-UHFFFAOYSA-N CC(N)OCCOCCO Chemical compound CC(N)OCCOCCO IDIHFYDGUBHGMP-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- WRLRISOTNFYPMU-UHFFFAOYSA-N [S].CC1=CC=CC=C1 Chemical compound [S].CC1=CC=CC=C1 WRLRISOTNFYPMU-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 229910000474 mercury oxide Inorganic materials 0.000 description 1
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical class [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 1
- SWVMLNPDTIFDDY-SBSPUUFOSA-N methyl (2r)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](N)CC1=CC=CC=C1 SWVMLNPDTIFDDY-SBSPUUFOSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/30—Preparation of optical isomers
- C07C227/34—Preparation of optical isomers by separation of optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/26—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/008—Supramolecular polymers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/86—Ring systems containing bridged rings containing four rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses polyethers urea bridging chiral molecular tweezer and its preparations and application.Shown in the structure such as formula (I) or formula (II) of the polyethers urea bridging chiral molecular tweezer.The present invention provides application of the polyethers urea bridging chiral molecular tweezer in identifying chiral molecules object, the chiral molecules object is D/L- amino acid ester hydrochlorides.The Molecular Tweezers that the present invention synthesizes have certain chiral Recognition performance to D/L- amino acid ester hydrochlorides, can be used for chiral Recognition separation enantiomter.
Description
(1) technical field
The present invention relates to a kind of containing there are two the chiral molecular tweezer compound of ent- beyerane diterpene skeletons and its preparation sides
Method and application in chiral Molecular Recognition field, belong to chiral Recognition separation field.
(2) background technology
Molecular recognition is the essential characteristic of biosystem, and plays an important role in vital movement.When a chiral mapping
After isomers enters life entity, two enantiomters can usually show completely different bioactivity, so chiral object
It is significantly that the enantiomter of matter, which carries out chiral Recognition separation,.Polyethers urea groups have the stronger intermolecular hydrogen of formation
Bond energy power, ent- beyerane type diterpene molecular skeletons have the hydrophobic outer wall of rigidity, the structure of concave surface and intrinsic asymmetry,
Using the asymmetry of ent- beyerane type diterpene molecular structures, novel surpassing with chiral recognition is researched and developed
Molecular compound has broad application prospects in fields such as functional material, medicine, biochemistry.
(3) invention content
Present invention aims at provide it is a kind of it is new with chiral Molecular Recognition function using polyethers urea groups as linker
Group, chiral molecular tweezer compound containing ent- beyerane skeletons and preparation method thereof and answering in chiral Recognition separation
With.
To achieve the above object, the present invention adopts the following technical scheme that：
The present invention provides polyethers urea bridging chiral molecular tweezer, shown in structure such as formula (I) or formula (II)：
The present invention provides a kind of preparation method of the polyethers urea bridging chiral molecular tweezer, the preparation method packets
It includes：Compound shown in formula (XIV) is dissolved in dichloromethane, is added shown in compound or formula (IX) shown in DIEA and formula (VIII)
Compound, room temperature reaction 6~for 24 hours, (preferably elution reagent is petroleum ether/acetone, wherein volume ratio to silica gel column chromatography on reaction solution
Petroleum ether: acetone=6:1) compound shown in compound or formula (II) shown in corresponding formula (I), is made；
Further, the ratio between compound and the amount of substance of DIEA shown in the formula (XIV) are 1：1~5 (preferably 1:2)；Institute
It is 2 that compound shown in formula (XIV), which is stated, with the ratio between amount of substance of compound shown in compound or formula (IX) shown in formula (VIII)：
0.5~2 (preferably 2:1)；The volumetric usage of the dichloromethane is calculated as 20~60mL/ with the quality of compound shown in formula (XIV)
g。
In the present invention, compound shown in compound, formula (IX) shown in compound, formula (VIII) shown in the formula (XIV)
It is known compound, preparation can refer to open source literature.
Specifically, compound shown in compound and formula (IX) shown in the formula (VIII) recommend as follows into
It is prepared by row：
(1) by NaBH4And I2It is added in anhydrous THF a, obtains mixed liquor, under nitrogen protection, under condition of ice bath slowly
The anhydrous THF b solution dissolved with L-phenylalanine shown in D-phenylalanine shown in formula (III) or formula (IV) is added dropwise, drips
It is brought rapidly up after finishing to back flow reaction 10~for 24 hours, reaction solution is cooled to room temperature, and methanol is slowly added dropwise until solution is clarified, decompression
Excess of solvent is boiled off, 10~30% KOH solution is added, 2~6h is stirred at room temperature, the post-treated obtained phases of obtained reaction solution a
Compound shown in compound or formula (VI) shown in the formula (V) answered；The D-phenylalanine or L-phenylalanine and NaBH4、I2Object
The ratio between amount of matter is 1：2~6：0.5~2；The volumetric usage of the THF a is in terms of the quality of D-phenylalanine or L-phenylalanine
For 10~40mL/g；The volumetric usage of the THF b is calculated as 10~40mL/g with the quality of D-phenylalanine or L-phenylalanine；
(2) diglycol is added in dichloromethane, stirring and dissolving under condition of ice bath is added portionwise to toluene sulphur
Acyl chlorides solid (preferably divides 5 batches of additions), then sodium hydrate solid (preferably dividing 3 batches of additions) is added portionwise, and is stirred in condition of ice bath
React 2~6h, compound shown in the post-treated obtained formulas (VII) of gained reaction solution b；The diglycol with to toluene sulphur
The ratio between amount of substance of acyl chlorides, sodium hydroxide is 1：1~3：1~6；The volumetric usage of the dichloromethane is diglycol
5~20 times of volume；
(3) NaH is added in anhydrous THF c, is added dropwise dissolved with formula made from step (1) under nitrogen protection, condition of ice bath
(V) the anhydrous THF d solution of compound shown in compound or formula (VI) shown in, after reacting at room temperature 1~4h, continue be added dropwise dissolved with
The anhydrous THF e solution of compound shown in formula (VII) made from step (2) continues at 48~96h of room temperature reaction, gained reaction
Liquid c is post-treated to be made compound shown in compound or formula (IX) shown in corresponding formula (VIII)；Compound shown in the formula (V)
Or the ratio between compound shown in formula (VI) and compound, the amount of substance of NaH shown in formula (VII) are 2：1：10~30；The THF c
Volumetric usage 20~50mL/g is calculated as with the quality of compound shown in compound shown in formula (V) or formula (VI)；The THF d's
Volumetric usage is calculated as 20~50mL/g with the quality of compound shown in compound shown in formula (V) or formula (VI)；The body of the THF e
Product dosage is calculated as 20~50mL/g with the quality of compound shown in compound shown in formula (V) or formula (VI)；
In above-mentioned preparation process, in step (1), the post-processing approach of the reaction solution a is：After reaction, reaction solution a
It is extracted with dichloromethane, merges organic layer, organic phase anhydrous Na2SO4It is dry, it filters, filtrate decompression is spin-dried for obtaining compound (V).
In step (2), the post-processing approach of the reaction solution b is：After reaction, it is anti-that ice water quenching is added in reaction solution b
It answers, is extracted with dichloromethane, organic layer is with 1%~20% hydrochloric acid solution, saturated common salt water washing, organic layer anhydrous Na2SO4
It is dry, it filters, decompression is spin-dried for, and recrystallizing methanol obtains compound (VII).
In step (3), the post-processing approach of the reaction solution c is：After reaction, water quenching reaction is added in reaction solution c,
Decompression boils off THF, with concentrated hydrochloric acid tune pH to 2~7, ethyl acetate washing, water phase Na2CO3PH to 9 or so is adjusted, ethyl acetate is used
Extraction, organic layer anhydrous Na2SO4It is dry, it filters, is spin-dried for give light yellow oil, neutral alumina column chromatography (200-300
Mesh) (preferably elution reagent is dichloromethane/ethyl alcohol, wherein volume ratio dichloromethane: ethyl alcohol=20:1) compound, is obtained
(VIII)。
The recommendation of compound shown in the formula (XIV) is prepared in accordance with the following steps：
(A) steviol glycoside shown in formula (X) is dissolved in 10wt%~20wt% sulfuric acid solutions, is stirred at 75~80 DEG C
5~6h is reacted, is cooled to room temperature later, is filtered, filter cake acetone recrystallization, compound shown in formula (XI) is made；It is described
It is (excellent that the volumetric usage of 10wt%~20wt% sulfuric acid solutions with the quality of steviol glycoside shown in formula (X) is calculated as 30~100mL/g
Select 50~70mL/g)；
(B) compound shown in formula (XI) made from step (A) dichloro Asia is dissolved in sough, under the conditions of 60~75 DEG C react 1~
3h, vacuum distillation remove extra dichloro Asia and sough, and obtain brown solid, and brown solid is recrystallized with n-hexane, and formula (XII) institute is made
Show compound；
(C) compound shown in formula (XII) made from step (B) is dissolved in acetone, NaN is added dropwise3It is dissolved in the solution of water a, in
15min is reacted at room temperature, adds water b quenching reactions, precipitation is precipitated, filters and dries, compound shown in formula (XIII) is made；Describedization
Close object (XII) and NaN3The ratio between the amount of substance be 1：1~5；The volumetric usage of the acetone is in terms of the quality of compound (XII)
For 10~60mL/g；The volumetric usage of the water a is calculated as 0.1~5mL/g with the quality of compound (XII)；The volume of the water b
Dosage is calculated as 20~200mL/g with the quality of compound (XII)；
(D) compound shown in formula (XIII) made from step (C) is dissolved in toluene, 2~20h of heating reflux reaction is evaporated off
Toluene is recrystallized with petroleum ether, and compound shown in formula (XIV) is made；The volumetric usage of the toluene is with compound (XIII)
Quality is calculated as 10~60mL/g；
In formula (X), Glu is the abbreviation of glucosyl group.
In the present invention, term " reaction solution a ", " reaction solution b ", " reaction solution c ", " reaction solution d ", " reaction solution e ", " reaction
Meaning not special liquid f " is only intended to distinguish the reaction in different step labeled as " a ", " b ", " c ", " d ", " e ", " f "
Liquid；Term " THF a ", " THF b ", " THF c ", " water a ", " water b " are therewith similarly.
Invention further provides the polyethers urea bridging chiral molecular tweezer answering in identifying chiral molecules object
With the chiral molecules object is D/L- amino acid ester hydrochlorides.
Preferably, the chiral molecules object is D/L- phenylalanine methyl ester hydrochlorides.
The present invention the experimental results showed that, host compound (I), (II) can form D- and l-amino acid ester hydrochloride
Super molecular complex, and have larger binding constant Ka, utilize the combination of compound (I) and D- and l-amino acid ester hydrochloride
The difference of constant, it can be achieved that both D- and l-amino acid ester hydrochloride separation.Specifically, compound (I) and D- phenylpropyl alcohol ammonia
The binding constant of acid methyl ester hydrochloride salt is more than the binding constant of compound (I) and L-phenylalanine methyl ester hydrochloride, due to this
The difference of binding constant, using compound (I) by D, the mixture of both L-phenylalanine methyl ester hydrochlorides separates；Change
It closes object (II) and the binding constant of L-phenylalanine methyl ester hydrochloride is more than compound (II) and D-phenylalanine methyl ester hydrochloride
Binding constant, also due to the difference of this binding constant separates phenylalanine methyl ester hydrochloride enantiomter.Therefore,
The Molecular Tweezers that the present invention synthesizes have certain chiral Recognition performance to D/L- amino acid ester hydrochlorides, can be used for chiral Recognition point
From enantiomter.
The beneficial effects of the present invention are：The present invention provides using polyethers urea groups as linking group, contain ent- pattra leaves
The chiral molecular tweezer of alkane skeleton, in terms of identifying chiral molecules object especially in terms of identifying D/L- amino acid ester hydrochlorides
With certain application prospect；It is provided by the present invention using polyethers urea groups as linking group, using ent- pattra leaves alkyl structure as hand
The Molecular Tweezers of property arm have many advantages, such as raw material be easy to get, adjustable structure, prepare it is succinct；Therefore it is expected in chiral Recognition separation field
It is applied.
(4) specific implementation mode
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in
This：
Embodiment 1：The preparation of D- phenylalaninols (V)
The anhydrous THF of 40mL, the NaBH of 1.52g (40mmol) are sequentially added in 250mL three neck round bottom flask4With
The I of 2.54g (10mmol)2.Under nitrogen protection, the D- phenylpropyl alcohols dissolved with 1.65g (10mmol) are slowly added dropwise under condition of ice bath
The anhydrous THF solution 40mL of propylhomoserin (III) is brought rapidly up after being added dropwise to back flow reaction 18h.Reaction solution is cooled to room temperature,
Methanol is slowly added dropwise until solution is clarified.Decompression boils off excess of solvent, and the KOH solution of 60mL 20% is added, 4h is stirred at room temperature.
The dichloromethane of reaction solution 30mL × 5 extracts, and merges organic layer, organic phase anhydrous Na2SO4It is dry, it filters, filtrate is taken to subtract
Pressure is spin-dried for obtaining white waxy solid, is directly used in reacts in next step without further purification.
Embodiment 2：The preparation of L- phenylalaninols (VI)
The D-phenylalanine (III) in embodiment 1 is replaced with L-phenylalanine (IV), other operations are obtained with embodiment 1
White waxy solid compound (VI) is directly used in reacts in next step without further purification.
Embodiment 3：The preparation of two tolysulfonyl ester (VII) of diethylene glycol (DEG)
4.74mL (0.05mol) diglycol, 45mL dichloromethanes are sequentially added in 100mL single necked round bottom flask
Alkane, under ice bath under the conditions of the paratoluensulfonyl chloride of 19.00g (0.1mol) is added after stirring and dissolving in five batches.It has been added portionwise
Bi Hou divides more batches and is slowly added to 6.00g (0.15mol) sodium hydrate solid, continues at condition of ice bath and be stirred to react 3h.Reaction solution
120mL ice water is added, is extracted with the dichloromethane of 50mL × 3, merges organic layer, use 10% hydrochloric acid solution of 50mL × 3 successively,
50mL saturated common salt water washings, organic layer anhydrous Na2SO4It is dry, it filters, decompression is spin-dried for obtaining compound as white solid (VII).
Recrystallizing methanol obtains white needle-like crystals compound (VII) 10.35g (0.025mol), yield：50%, fusing point：71-72℃.
Embodiment 4：The preparation of compound (VIII)
The anhydrous THF that the NaH and 50mL of 2.40g (100mmol) are sequentially added in 250mL three neck round bottom flask, in nitrogen
The D- phenylalaninols (V) prepared according to 1 method of embodiment dissolved with 1.51g (10mmol) are added dropwise under gas shielded under condition of ice bath
Anhydrous THF solution 50mL.It is added dropwise, after reacting at room temperature 2h, continues what dropwise addition was prepared dissolved with 2.07g (5mmol) embodiment 3
The anhydrous THF solution 50mL of two tolysulfonyl ester (VII) of diethylene glycol (DEG) continues at room temperature reaction 72h.Water 200mL, decompression is added to steam
The THF in solution is removed, with concentrated hydrochloric acid tune pH to highly acid, is washed with the ethyl acetate of 50mL × 3.Water phase Na2CO3Adjust pH to 9
Left and right is extracted with the ethyl acetate of 50mL × 3, merges organic layer, organic layer anhydrous Na2SO4It is dry, it filters, decompression is spin-dried for
Light yellow oil.Neutral alumina column chromatography (200-300 mesh) (dichloromethane: ethyl alcohol=20:1), product is light yellow oil
Shape compound (VIII) 0.74g (2.0mmol), yield：20% (in terms of D-phenylalanine).
Embodiment 5：The preparation of compound (IX)
The L- phenylalaninols (VI) prepared according to 2 method of embodiment with 10mmol are instead of the D- phenylalaninols in embodiment 4
(V), other operations obtain pale yellowish oil compound (IX) 0.67g (1.8mmol), yield with embodiment 4：18% (with L- benzene
Alanine meter).
Embodiment 6：The preparation of compound (XI)
Steviol glycoside (X) 10g is placed in the round-bottomed flask of 1000mL, is slowly added to the dilution heat of sulfuric acid 600mL of 10wt%,
Magnetic agitation, 75 DEG C of oil bath.After reacting 1h, there is a small amount of yellow fluffy solid to generate, the reaction was continued 4h stops reaction and being cooled to room
Temperature.It filters, obtained yellow solid will be filtered is transferred in the single-necked flask of 100mL and use acetone recrystallization, it is cooling to place, have
White crystal is slowly precipitated, and compound (XI) 2.98g is drying to obtain after filtering.Yield：65.1%, fusing point：263-264℃.1H-
NMR(500MHz,CDCl3)δ(ppm):2.64 (dd, J=18.6,3.8Hz, 1H, 15-Hα), 2.17 (d, J=13.4Hz, 1H, 3-
Heq), 1.89-1.79 (m, 3H, 6-Heq, 2-Hax, 15-Hβ), 1.74-1.66 (m, 3H, 1-Heq, 11-Heq, 7-Heq),1.53
(dd, J=11.5,2.8Hz, 1H, 14-Heq), 1.50 (dd, J=13.2,4.1Hz, 1H, 7-Hax), 1.26 (s, 3H, 18-CH3),
0.98(s,3H,17-CH3),0.79(s,3H,20-CH3).
Embodiment 7：The preparation of compound (XII)
The compound (XI) (6.29mmol, 2.0g) for weighing the preparation of embodiment 6 in 50ml round-bottomed flasks, is added thereto
2ml thionyl chlorides react 1.5h under the conditions of 70 DEG C, steam extra thionyl chloride, obtain brown solid, solid to brown
The n-hexane of 45ml is added in body, flows back 10 minutes, filters to obtain liquid while hot, stands recrystallization, obtains yellow solid i.e. compound
(XII), yield：44.5%.
Embodiment 8：The preparation of compound (XIII)
In the single necked round bottom flask of 100mL, the 7 freshly prepared compound of embodiment of 1.01g (3mmol) is sequentially added
(XII), acetone 30mL, after compound (XII) is completely dissolved, by NaN30.3g (4.6mmol) is dissolved in 0.5mL water, slowly
It is added dropwise to reaction solution, reaction 15min is stirred at room temperature.Add water 60mL, a large amount of yellow mercury oxides are precipitated, filters, appropriate water washing is used in combination
Filter cake.Filter cake is taken to dry to obtain light yellow powder solid chemical compound (XIII) 9.36g (2.73mmol), yield in air：
91%.137-139 DEG C of fusing point, IR ν KmBaxr(cm-1):2144,1195.
Embodiment 9：The preparation of compound (XIV)
The compound (XIII) of the preparation of 0.68g (2mmol) embodiment 8, toluene are sequentially added in the single necked round bottom flask of 100mL
30mL, back flow reaction 5h.Normal pressure boils off extra toluene, is recrystallized with 60mL petroleum ethers, and light yellow solid Compound (XIV) 0.41g is precipitated
(1.30mmol), yield 65%.116-118 DEG C of fusing point,
Embodiment 10：The preparation of compound (I)
Sequentially add the compound (XIV) that 0.63g (2mmol) is prepared according to 9 method of embodiment in the single-necked flask of 50mL, two
Compound (VIII) prepared by DIEA and 0.37g (1mmol) embodiment 4 of chloromethanes 25mL, 0.52g (4mmol), is stirred at room temperature reaction
12h.Reaction solution directly mixes sample.Silica gel column chromatography (petroleum ether: acetone=6:1), product is white powdery solids compound (I)
0.24g (0.33mmol), yield：32%, fusing point：164-165℃.[α]D 20-29.98(c 5.70,CH2Cl2)； 1H-NMR(500MHz,CDCl3):δ (ppm) 7.28-7.25 (m, 4H), 7.23-7.18 (m, 6H), 5.17 (d, J=8.5Hz,
2H), 4.44 (s, 2H), 3.99-3.97 (m, 2H), 3.66-3.59 (m, 8H), 3.46 (dd, J=9.5,4.2Hz, 2H), 3.38
(dd, J=9.5,4.0Hz, 2H), 2.88-2.80 (m, 4H), 2.74 (d, J=13.7Hz, 2H), 2.46 (dd, J=18.5,
3.8Hz,2H),1.84-1.64(m,10H),1.61-1.55(m,8H),1.38(s,6H),1.30-1.18(m,8H),1.10-
1.03(m,4H),0.99(s,6H),0.96(s,6H),0.89-0.84(m,6H)；13C-NMR(125MHz,CDCl3):δ(ppm)
222.9,157.3,138.7,129.4,128.3,126.2,71.7,70.4,70.2,56.7,55.1,54.8,54.3,504,
48.9,48.8,41.0,39.4,39.0,38.2,37.6,37.2,36.8,29.7,27.9,19.91,19.86,19.5,17.7,
15.1,14.1；HRMS(ESI):calcd.For C62H90N4NaO7[M+Na+]1025.6702；found 1025.6720.
Embodiment 11：The preparation of compound (II)
The compound (VIII) in embodiment 10 is replaced with compound (IX) prepared by embodiment 5, other operations are the same as implementation
Example 10 obtains white powdery solids compound (II) 0.22g (0.30mmol), yield：30%, fusing point：116-117℃.
[α]D 20-55.71(c 6.66,CH2Cl2)； 1H-NMR(500MHz,CDCl3):δ(ppm)7.27-
7.23 (m, 4H), 7.23-7.18 (m, 6H), 5.19 (d, J=8.6Hz, 2H), 4.40 (s, 2H), 4.06 (s, 2H), 3.72-
3.57 (m, 8H), 3.42 (dd, J=9.6,4.8Hz, 2H), 3.36 (dd, J=9.6,3.8Hz, 2H), 2.90-2.82 (m, 4H),
2.80 (d, J=13.8Hz, 2H), 2.61 (dd, J=18.5,3.1Hz, 2H), 1.81-1.62 (m, 10H), 1.60-1.52 (m,
8H),1.37(s,6H),1.32-1.25(m,8H),1.23-1.20(m,4H),0.99(s,6H),0.98(s,6H),0.92-
0.84(m,6H)；13C-NMR(125MHz,CDCl3):δ(ppm)222.9,156.9,138.5,129.6,128.3,126.2,
71.7,70.4,70.3,56.7,55.1,54.8,54.2,50.3,48.8,48.7,40.9,39.4,39.3,38.0,37.6,
37.2,36.8,29.7,27.9,19.9,19.4,17.7,15.0,14.1；HRMS(ESI):calcd.For C62H90N4NaO7[M
+Na+]1025.6702；found1025.6692.
Embodiment 12：Ultraviolet spectrophotometer method measures recognition performance
Using methanol as solvent, the concentration of stationary body Molecular Tweezers is 2 × 10-5-9×10-5Between mol/L, it is continuously added
Guest molecule (D- amino acid methyl ester hydrochlorides or l-amino acid methyl ester hydrochloride), makes its concentration 8 × 10-4-5×10-3mol/
Change between L, using the object solutions as controls of same concentration, measures the absorbance value of each group complex solution.Experimentation
In, increase with guest compound concentration is added, host compound characteristic absorption rises in regularity, illustrates host molecule and visitor
There is non-covalent bond effects between body molecule, produce identification mating reaction.Host molecule clamps (I) and (II) to what is investigated
Amino acid methyl ester hydrochloride, when object concentration is far longer than body concentration, using the Benesi-Hildebrand equations of modification
Linear fit is carried out, with 1/ [G0] to 1/ Δ A mappings, good linear relationship is given, 1 is formd between Subjective and Objective：1 type is super
Molecular complex is listed in table 1 according to straight slope and the calculated binding constant of intercept.
Host molecule clamps binding constant (Ka) He Jibu of (I), (II) and guest molecule in methanol solution at 1 25 DEG C of table
(- Δ the G of this free energy0) situation of change
Supermolecule can be formed to D- and l-amino acid ester hydrochloride by visible host compound (I), (II) synthesized of table 1
Complex, and have larger binding constant Ka.Using a host compound pair chiral enantiomter binding constant
Difference is separated the mixture of D types and L-type amino-acid ester with it, realizes chiral resolution.
Comparative example：
With compound (XIV) be raw material, using dichloromethane solution as solvent respectively with (1R, 2R) -1,2- cyclohexanediamine
(1S, 2S) -1,2- cyclohexanediamine reacts, and generates chiral molecular tweezer compound (R, R) -1 and (S, S) -1.Design synthetic route
It is as follows：
The preparation of (R, R) -1
The compound (XIV) of 0.63g (2mmol), dichloromethane 25mL, 0.52g are sequentially added in the single-necked flask of 100mL
Reaction 12h is stirred at room temperature in the DIEA of (4mmol), (1R, 2R)-cyclohexanediamine 0.23g (2mmol).The washing of reaction solution 30mL × 3
It washs, organic phase anhydrous Na2SO4It is dry, it filters, takes filtrate decompression to be spin-dried for, obtain white powder crude product.Silica gel column chromatography (petroleum ether:
Acetone=6:1), product is white powdery solids 0.35g (0.48mmol), yield：48%, fusing point：204-205℃.[α]D 20-66.3
(c 5.00,CH2Cl2)； 1H-NMR
(500MHz,CDCl3):δ (ppm) 5.33 (d, J=17.1Hz, 2H), 4.18 (s, 2H), 3.31 (s, 2H), 2.68 (dd, J=
22.2,3.5Hz, 2H), 2.64 (d, J=16.2Hz, 2H), 2.05-2.02 (m, 2H), 1.84-1.78 (m, 6H), 1.71-1.63
(m, 10H), 1.59-1.51 (m, 6H), 1.44 (dd, J=11.7,3.5Hz, 2H), 1.39 (s, 6H), 1.34 (dd, J=12.9,
2.5Hz, 2H), 1.28-1.20 (m, 8H), 1.09-1.07 (m, 2H), 1.02 (d, J=12.5Hz, 2H), 0.99 (s, 6H),
0.97(s,6H),0.93-0.86(m,4H)；13C-NMR(125MHz,CDCl3)δ223.0,157.9,56.8,55.1,54.8,
54.5,54.3,48.9,48.8,41.0,39.3,39.3,37.5,37.2,37.0,33.6,28.0,25.0,19.9,19.9,
19.6,17.8,15.2；HRMS(ESI):calcd.For C46H73N4O4[M+H+]745.5626；found 745.5616.
The preparation of (S, S) -1
Change (1R, 2R)-cyclohexanediamine into (1S, 2S)-cyclohexanediamine, remaining operating procedure and compound (R, R) -1
It synthesizes identical.Product is white powdery solids 0.42g (0.42mmol), yield：56%, fusing point：255-256℃.[α]D 20-
25.6(c 5.01,CH2Cl2)； 1H-NMR(500MHz,CDCl3):δ (ppm) 5.93 (s, 2H), 4.12 (s, 2H), 3.34 (d, J=7.4Hz, 2H), 2.80 (d, J
=13.7Hz, 2H), 2.68 (dd, J=18.5,3.6Hz, 2H), 2.00 (d, J=12.4Hz, 2H), 1.84-1.80 (m, 6H),
1.74-1.64(m,10H),1.61-1.56(m,6H),1.45-1.39(m,6H),1.37(s,6H),1.28-1.23(m,8H),
1.09-1.06 (m, 2H), 1.03 (d, J=5.9Hz, 2H), 1.00 (s, 6H), 0.99 (s, 6H), 0.93-0.84 (m, 4H)；13C-
NMR(125MHz,CDCl3):δ(ppm)222.6,158.0,56.7,55.2,54.9,54.5,54.3,48.8,41.1,39,4,
39.3,37.6,37.2,36.7,33.6,28.0,25.1,19.9,19.3,17.7,15.1；HRMS(ESI):calcd.For
C46H73N4O4[M+H+]745.5626；found 745.5657.
The Molecular Tweezers based on compound (R, R) -1 and (S, S) -1, using methanol as solvent, stationary body Molecular Tweezers
Concentration is 2 × 10-5-9×10-5Between mol/L, guest molecule D/L- phenylalanine methyl ester hydrochlorides are continuously added, its concentration is made
8 × 10-4-5×10-3Change between mol/L, using the object solutions as controls of same concentration, measures each group complex solution
Absorbance value.Ultraviolet titration the experimental results showed that, D and the chiral Molecular Tweezers compound of L-phenylalanine methyl ester hydrochloride
The absorbance value of (R, R) -1 and (S, S) -1 each group complex solution is not in regular increasing or decreasing, chiral molecular tweezer compound
(R, R) -1 and (S, S) -1 pair of D/L- phenylalanine methyl ester hydrochloride do not have chiral recognition.
Claims (5)
1. shown in polyethers urea bridging chiral molecular tweezer, structure such as formula (I) or formula (II)：
2. a kind of preparation method of polyethers urea bridging chiral molecular tweezer as described in claim 1, the preparation method include：
Compound shown in formula (XIV) is dissolved in dichloromethane, compound or formula (IX) shownization shown in DIEA and formula (VIII) is added
Conjunction object, room temperature reaction 6~for 24 hours, silica gel column chromatography on reaction solution is made shown in compound or formula (II) shown in corresponding formula (I)
Compound；
3. preparation method as claimed in claim 2, it is characterised in that：The substance of compound and DIEA shown in the formula (XIV)
The ratio between amount be 1：1~5；Compound shown in the formula (XIV) and compound shown in compound or formula (IX) shown in formula (VIII)
The ratio between the amount of substance be 2：0.5~2；The volumetric usage of the dichloromethane is calculated as with the quality of compound shown in formula (XIV)
20~60mL/g.
4. application of the polyethers urea bridging chiral molecular tweezer as described in claim 1 in identifying chiral molecules object, described
Chiral molecules object is D/L- amino acid ester hydrochlorides.
5. application as claimed in claim 4, it is characterised in that：The chiral molecules object is D/L- phenyalanine methyl ester salt
Hydrochlorate.
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| CN102718657A (en) * | 2012-06-08 | 2012-10-10 | 浙江工业大学 | Isosteviol compound as well as preparation method and application thereof |
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| CN105541633A (en) * | 2015-12-16 | 2016-05-04 | 浙江工业大学 | Open-chain chiral crown ether containing ent-beyerane skeleton and preparation and application thereof |
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| CN102718657A (en) * | 2012-06-08 | 2012-10-10 | 浙江工业大学 | Isosteviol compound as well as preparation method and application thereof |
| CN105399644A (en) * | 2015-12-11 | 2016-03-16 | 浙江工业大学 | Molecular tweezer compounds with (1S,2S)-1,2-cyclohexanediamine as spacer group and isosteviol as chiral arm, and preparation method and application thereof |
| CN105601528A (en) * | 2015-12-11 | 2016-05-25 | 浙江工业大学 | Molecular tweezer compound with ent-beyerane diterpene as chiral arm, and preparation method and application thereof |
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