CN106518852A - 2-methyl-2-(5-fluorouracil) carbonyl trimethylene carbonate and its preparation method and use - Google Patents
2-methyl-2-(5-fluorouracil) carbonyl trimethylene carbonate and its preparation method and use Download PDFInfo
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- CN106518852A CN106518852A CN201610949989.XA CN201610949989A CN106518852A CN 106518852 A CN106518852 A CN 106518852A CN 201610949989 A CN201610949989 A CN 201610949989A CN 106518852 A CN106518852 A CN 106518852A
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- methyl
- fluorouracil
- trimethylene carbonate
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- carbonyl
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- -1 carbonyl trimethylene Chemical group 0.000 title claims abstract description 32
- 229960002949 fluorouracil Drugs 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000013078 crystal Substances 0.000 claims abstract description 11
- 229920000515 polycarbonate Polymers 0.000 claims abstract description 9
- 239000004417 polycarbonate Substances 0.000 claims abstract description 9
- 230000004224 protection Effects 0.000 claims abstract description 4
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 3
- PTBDIHRZYDMNKB-UHFFFAOYSA-N 2,2-Bis(hydroxymethyl)propionic acid Chemical compound OCC(C)(CO)C(O)=O PTBDIHRZYDMNKB-UHFFFAOYSA-N 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000012141 concentrate Substances 0.000 claims description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- VGFNGLUDOVQRNF-UHFFFAOYSA-N benzyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate Chemical compound OCC(C)(CO)C(=O)OCC1=CC=CC=C1 VGFNGLUDOVQRNF-UHFFFAOYSA-N 0.000 claims 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 claims 1
- 239000012830 cancer therapeutic Substances 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- 229940126585 therapeutic drug Drugs 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 9
- 239000000178 monomer Substances 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 7
- 206010028980 Neoplasm Diseases 0.000 abstract description 5
- 201000011510 cancer Diseases 0.000 abstract description 5
- 150000005676 cyclic carbonates Chemical class 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 238000006482 condensation reaction Methods 0.000 abstract description 2
- 238000007363 ring formation reaction Methods 0.000 abstract description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 229940041181 antineoplastic drug Drugs 0.000 abstract 1
- 238000010511 deprotection reaction Methods 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 235000019260 propionic acid Nutrition 0.000 description 6
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 208000035126 Facies Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 150000004672 propanoic acids Chemical class 0.000 description 3
- 238000007151 ring opening polymerisation reaction Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- VHOMAPWVLKRQAZ-UHFFFAOYSA-N Benzyl propionate Chemical class CCC(=O)OCC1=CC=CC=C1 VHOMAPWVLKRQAZ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 229920001963 Synthetic biodegradable polymer Polymers 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000012644 addition polymerization Methods 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
- C08G64/02—Aliphatic polycarbonates
- C08G64/0208—Aliphatic polycarbonates saturated
- C08G64/0225—Aliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen
- C08G64/0233—Aliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen containing halogens
-
- 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
- C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
- C08G64/02—Aliphatic polycarbonates
- C08G64/0208—Aliphatic polycarbonates saturated
- C08G64/0225—Aliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen
- C08G64/0241—Aliphatic polycarbonates saturated containing atoms other than carbon, hydrogen or oxygen containing nitrogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polyesters Or Polycarbonates (AREA)
Abstract
本发明提供了一种能够合成生物可降解聚碳酸酯的单体材料2‑甲基‑2‑(5‑氟尿嘧啶)羰基三亚甲基碳酸酯，上述2‑甲基‑2‑(5‑氟尿嘧啶)羰基三亚甲基碳酸酯为白色晶体，分子式C10H9FN2O6，分子量为272。该物质的合成路线为：从2，2‑二羟甲基丙酸出发，经保护、关环、脱保护、取代以及缩合反应，制备了新型六元环状碳酸酯单体2‑甲基‑2‑(5‑氟尿嘧啶)羰基三亚甲基碳酸酯。该物质能够用于合成具有生物相容性的功能化聚碳酸酯，由于其侧链5‑氟尿嘧是一种抗癌药物，因此所合成的产物在具备癌症治疗效果的基础上，又具备了良好的生物相容性，能够用于制备癌症治疗药物中，具有较高的应用价值。
The invention provides a monomer material 2-methyl-2-(5-fluorouracil) carbonyl trimethylene carbonate capable of synthesizing biodegradable polycarbonate, the above-mentioned 2-methyl-2-(5-fluorouracil) Carbonyltrimethylene carbonate is a white crystal with a molecular formula of C 10 H 9 FN 2 O 6 and a molecular weight of 272. The synthetic route of this substance is: starting from 2,2-dimethylolpropionic acid, through protection, ring closure, deprotection, substitution and condensation reactions, a new six-membered cyclic carbonate monomer 2-methyl- 2‑(5‑Fluorouracil) carbonyl trimethylene carbonate. This substance can be used to synthesize functionalized polycarbonate with biocompatibility, because its side chain 5-fluorouracil is an anticancer drug, so the synthesized product has cancer treatment effect and has It has good biocompatibility, can be used in the preparation of cancer treatment drugs, and has high application value.
Description
Technical field
The invention provides a kind of biodegradable polycarbonates and its production and use, more particularly to
2- methyl -2- (5-fluorouracil) carbonyl trimethylene carbonates, belong to biomedical materials field.
Background technology
Used as a class synthetic Biodegradable polymer material, fatty poly-ester carbonate has good bio-compatible
Property, biodegradability and physical and mechanical propertiess, and species is a lot, in surgical sewing thread, bone immobilizing material, medicine control
The field such as system release and organizational project is increasingly taken seriously.The synthetic method of fatty poly-ester carbonate mainly have ester-interchange method,
Phosgene condensation method, epoxide and carbon dioxide addition polymerization process and cyclic carbonate monomer ring-opening polymerisation method.Wherein, ring-type
Carbonate monomer ring-opening polymerisation method has the advantages that polymerization process heat effect is low, polymerization speed is fast and molecular weight of product is high,
Become the topmost method of synthctic fat adoption carbonic ester.Different functional groups are introduced in cyclic carbonate monomer, for example
Carboxyl, amino, hydroxyl etc., can provide further chemical modification to fatty poly-ester carbonate.Cyclic carbonate monomer species
It is various, various fatty poly-ester carbonate can be prepared by ring-opening polymerisation.
The content of the invention
The invention provides a kind of monomer material 2- methyl -2- (5- fluorine urine for being capable of synthesising biological degradable polycarbonate
Pyrimidine) carbonyl trimethylene carbonate, its structural formula is：
Above-mentioned 2- methyl -2- (5-fluorouracil) carbonyls trimethylene carbonate be white crystal, molecular formula C10H9FN2O6, point
Son amount is 272.
Present invention also offers the preparation method of the material, comprises the following steps：(1), by 2,2- dihydromethyl propionic acids and
Cylite reacting by heating in a solvent, removes solvent after completion of the reaction, after separating organic faciess and washing, be dried, concentrate, then carries out
Recrystallization is simultaneously dried, and obtains 2,2- dihydromethyl propionic acid benzyl esters；
(2), with triethylamine as catalyst, tetrahydrofuran is solvent, by 2,2- dihydromethyl propionic acids benzyl ester and chloro-carbonic acid second
Ester reacts at room temperature, filters after the completion of reaction, filtrate concentration is carried out recrystallization and is dried, obtain 2- methyl -2- benzyloxy carbonyls
Base trimethylene carbonate；
(3), 2- methyl -2- benzyloxycarbonyl group trimethylene carbonates are dissolved in solvent, and add palladium/carbon catalyst,
Then it is sufficiently stirred in a hydrogen atmosphere making which slough benzyl protection, filters after the completion of reaction, makes after filtrate is concentrated and dried
Obtain 2- methyl -2- carbonyl trimethylene carbonates；
(4), with tetrahydrofuran as solvent, 2- methyl -2- carbonyls trimethylene carbonate and oxalyl chloride are filled at room temperature
Divide reaction, remove solvent after completion of the reaction, obtain 2- methyl -2- acyl chlorides trimethylene carbonates；
(5), 2- methyl -2- acyl chlorides trimethylene carbonate and 5-fluorouracil are dissolved in ethyl acetate, in room temperature
Lower reaction, is filtered after completion of the reaction, adds excessive absolute ether, separate out white crystal, white crystal is tied again after filtrate concentration
Crystalline substance, that is, be obtained final product 2- methyl -2- (5-fluorouracil) carbonyl trimethylene carbonates.
In step (1), solvent is N, and N '-dimethyl Methanamide, heating-up temperature are 100 DEG C, and the response time is 16 hours.
In step (3), solvent is ethyl acetate, and mixing time is 48 hours.
2- methyl -2- (5-fluorouracil) provided by the present invention carbonyl trimethylene carbonate can be used in synthesis to be had
The functional polycarbonates of biocompatibility, are a kind of cancer therapy drugs as its side chain 5- fluorine urine is phonetic, therefore synthesized product
On the basis of possessing treatment of cancer effect, but also with good biocompatibility, can be used in preparing cancer treatment drugs
In, with higher using value.The prices of raw materials simultaneously used in the preparation method of the present invention are cheap, wide material sources,
Preparation process is simple.
Description of the drawings
Structural formulas of the Fig. 1 for 2- methyl -2- (5-fluorouracil) provided by the present invention carbonyl trimethylene carbonate；
Synthetic routes of the Fig. 2 for 2- methyl -2- (5-fluorouracil) provided by the present invention carbonyl trimethylene carbonate
Figure.
Specific embodiment
2- methyl -2- (5-fluorouracil) carbonyl trimethylene carbonates provided in the embodiment of the present invention, its structure
Formula is as shown in figure 1, the synthetic route of the material is as shown in Figure 2：Set out from 2,2- dihydromethyl propionic acids, Jing protections, cyclization, remove-insurance
Shield, replacement and condensation reaction, are prepared for new six-membered cyclic carbonates monomer 2- methyl -2- (5-fluorouracil) carbonyls Sanya
Methyl carbonic.Detailed specific description is done with reference to the above-mentioned synthetic method of specific embodiment sheet：
Embodiment 1
Synthesis step employed in the present embodiment is as follows：
(1), the preparation of 2,2- dihydromethyl propionic acids benzyl ester：By 45.0 grams of 2,2- dihydromethyl propionic acids, 23.0 grams of hydroxides
Potassium and 250 milliliters of N, N '-dimethyl Methanamide are placed in 500 milliliters of round-bottomed flasks, heated and stirred 1 hour at 100 DEG C, are formed
Homogeneous transparent solution.69.0 grams of cylites drop to above-mentioned solution, and at 100 DEG C continue heated and stirred 16 hours.Question response
After cooling, removal of solvent under reduced pressure.300 milliliters of ethyl acetate, 300 ml n-hexanes and 200 milliliters of water are added in residue, are separated
Organic faciess, and washed with 200 milliliters, organic faciess are dried with anhydrous magnesium sulfate, concentration.The solid re crystallization from toluene for obtaining, 40
DEG C vacuum drying, obtain white crystal, yield is 73%.
Nuclear magnetic resoance spectrum result is as follows：1H NMR(CDCl3, ppm):7.36 (m, 5H, Ph), 5.21 (s, 2H, PhCH2),
3.94 (d, 2H, J=10.8Hz, CH2OH), 3.73 (d, 2H, J=10.8Hz, CH2OH), 1.08 (s, 3H, CH3)。
(2), the preparation of 2- methyl -2- benzyloxycarbonyl group trimethylene carbonates：By 22.4 grams of 2,2- dihydromethyl propionic acid benzyls
Ester and 28.0 grams of ethyl chloroformates and 600 milliliters of anhydrous tetrahydro furans are placed in 1000 milliliters of round-bottomed flasks, are stirred in ice bath.
28.0 grams of triethylamines are dropped in above-mentioned solution, are dripped within about 30 minutes.Ice bath is withdrawn, under room temperature, continues stirring 2 hours.Cross
Filter, uses tetrahydrofuran and ether mixed solvent recrystallization, 40 DEG C of vacuum drying to obtain white crystal after filtrate concentration, yield is
85%.
Infrared results are as follows：FT-IR:V=1754cm-1(C=O).1H NMR(CDCl3, ppm):7.37 (m, 5H, Ph),
5.22 (s, 2H, PhCH2), 4.71 (d, 2H, J=10.8Hz, CH2O), 4.21 (d, 2H, J=10.8Hz, CH2O), 1.34 (s,
3H, CH3)。
(3), the preparation of 2- methyl -2- carbonyl trimethylene carbonates：By 5.0 grams of three methylenes of 2- methyl -2- benzyloxycarbonyl groups
Base carbonic ester is dissolved in 50 milliliters of ethyl acetate, and adds 250 milligrams of Pd/C (10wt%).Pumping, is filled with hydrogen, so repeats
Three times.After being stirred at room temperature 48 hours in hydrogen atmosphere, filter, wash filtering residue several times with methanol.Merging filtrate, concentration, 40 DEG C
Vacuum drying, obtains white solid, and yield is 98%.
Nuclear magnetic resoance spectrum result is as follows：1H NMR(DMSO-d6, ppm):13.41 (br, 1H, COOH), 4.53 (d, 2H, J=
10.8Hz, CH2O), 4.31 (d, 2H, J=10.8Hz, CH2O), 1.15 (s, 3H, CH3)。
(4), the preparation of 2- methyl -2- acyl chlorides trimethylene carbonates：By 1.6 grams of 2- methyl -2- carbonyl trimethylene carbon
Acid esters, 1.3 grams of oxalyl chlorides and 50 milliliters of anhydrous tetrahydro furans are placed in 100 milliliters of round-bottomed flasks, are reacted 1 hour under room temperature.It is dense
Contracting obtains light yellow solid except solvent, and yield is 100%.
Nuclear magnetic resoance spectrum result is as follows：1H NMR(CDCl3, ppm):4.52 (d, 2H, J=10.8Hz, CH2O), 4.24 (d,
2H, J=10.8Hz, CH2O), 1.24 (s, 3H, CH3)。
(5), the preparation of 2- methyl -2- (5-fluorouracil) carbonyl trimethylene carbonate：By 1.78 grams of 2- methyl -2- acyls
Chlorine trimethylene carbonate, 1.30 grams of 5-fluorouracil, 1.1 grams of triethylamines and 50 milliliters of ethyl acetate are placed in 50 milliliters of round bottoms and burn
In bottle, react 3 hours under room temperature.Filter, add excessive absolute ether after filtrate concentration, separate out white crystal, and use tetrahydrochysene furan
Mutter and the mixed solvent recrystallization that absolute ether volume ratio is 1 to 3 three times, obtain white crystal, yield is 79%.
By infrared (FT-IR), nuclear magnetic resoance spectrum (1H NMR and13C NMR) and elementary analysiss (EA) phenetic analysis, it was demonstrated that
The white crystal is 2- methyl -2- (5-fluorouracil) carbonyl trimethylene carbonates.FT-IR:V=1749cm-1(C=O), v
=1662cm-1(CONH I), v=1524cm-1(CONH II)。1H NMR(CDCl3, ppm):7.35 (d, 1H, CH=CF),
4.48 (d, 2H, J=10.8Hz, CH2O), 4.17 (d, 2H, J=10.8Hz, CH2O), 1.28 (s, 3H, CH3)。13C NMR
(CDCl3, ppm):179.1,159.1,151.3,149.7,139.1,107.3,80.7,31.9,19.6.C10H9FN2O6
272.04:Calad.C 44.13, H 3.33, N 10.29；Found C 48.64, H 4.32, N 12.13.
Embodiment 2
2- methyl -2- (5-fluorouracil) carbonyls trimethylene carbonate prepared in upper embodiment is used for synthesizing tool
There are the functional polycarbonates of biocompatibility, concrete grammar is as follows：By 0.544 gram of 2- methyl -2- (5-fluorouracil) carbonyl
Trimethylene carbonate and 4.6 milligrams of diazabicylos are dissolved in 2 milliliters of dichloromethane, are reacted 5 hours under room temperature.With 50 milliliters
Normal hexane is precipitated, and resulting polymers are vacuum dried at 40 DEG C, and yield is 95.8%.Number-average molecular weight is 9400, and polydispersion refers to
Number is 1.21.
Infrared results are as follows：FT-IR:V=1755cm-1(C=O), v=1652cm-1(CONH I), v=1538cm-1
(CONH II)。1H NMR(CDCl3, ppm):7.38 (br, 1H, CH=CF), 4.52-4.21 (m, 4H, CH2O), 1.22 (s, 3H,
CH3)。
5-fluorouracil in the functional polycarbonates on side chain is a kind of cancer therapy drug, therefore the material can be used
In cancer treatment drugs are prepared, and the biodegradation character possessed due to its own, therefore prepared medicine has
Good biocompatibility.
Claims (5)
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