CN109111445A - 5 '-furoyl esters -3'-Deoxyadenosine synthetic method and application - Google Patents

5 '-furoyl esters -3'-Deoxyadenosine synthetic method and application Download PDF

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CN109111445A
CN109111445A CN201811297614.5A CN201811297614A CN109111445A CN 109111445 A CN109111445 A CN 109111445A CN 201811297614 A CN201811297614 A CN 201811297614A CN 109111445 A CN109111445 A CN 109111445A
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deoxyadenosine
furoyl
synthetic method
cordycepin
ester
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CN109111445B (en
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崔琳琳
李文兰
张群利
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Harbin University of Commerce
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    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
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    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
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Abstract

5 '-furoyl esters -3'-Deoxyadenosine synthetic method and application, it belongs to the analog synthesis technical field of cordycepin.Preparation method of the present invention is to weigh cordycepin bulk pharmaceutical chemicals and anhydrous pyridine respectively, load weighted cordycepin bulk pharmaceutical chemicals are added in anhydrous pyridine, mixed solution is obtained after stirring and dissolving, in nitrogen protection, under conditions of magnetic force heating stirring, the furoyl chloride that certain mass is slowly added dropwise is reacted, reaction process is monitored with thin-layer chromatography, it is evaporated under reduced pressure after reaction, obtain paste product, after being dissolved with distilled water, it is extracted with ethyl acetate 3 times, merge organic phase solution, vacuum distillation removes organic solvent, it obtains solid powder mixture and column chromatography silica gel mixes, the method of dry method loading carries out column chromatography, obtain 5 '-furoyl esters -3'-Deoxyadenosine.Analog of the present invention for cordycepin synthesizes.

Description

5 '-furoyl esters -3'-Deoxyadenosine synthetic method and application
Technical field
The invention belongs to the analog synthesis technical fields of cordycepin；More particularly to 5'- furoyl ester -3'- deoxidation gland The synthetic method and application of glycosides.
Background technique
Cordycepin is the analog of adenosine, also known as 3'-Deoxyadenosine, and early in nineteen fifty-one, German Cunningham etc. is just Separation discovery cordycepin (Cordycepin), is first from the culturing filtrate of China traditional Chinese medicine Cordyceps militaris (Cordyceps) A nucleosides antibiotics separated from fungi, cordyceps sinensis are known as antitumor, anti-leukocythemia, antibacterial, immunological regulation, remove body Various pharmacological actions such as interior free radical.Currently, the research of cordycepin have become in pharmaceutical chemistry now one it is extremely living The field of jump.
Tumor disease is one of higher disease of current disease incidence, in recent years, as the active constituent in cordyceps sinensis, worm The research of careless element (3'-Deoxyadenosine) pharmacological mechanism especially Anticancer Effect and Mechanism has become extremely active research neck One of domain.It is reported that cordycepin has growth inhibition effect, so that cordycepin is by extensive as potential antitumor pharmacy object Research.
Summary of the invention
It is an object of the present invention to provide the synthetic methods and application of a kind of 5'- furoyl ester -3'-Deoxyadenosine.
The invention is realized by the following technical scheme:
A kind of synthetic method of 5'- furoyl ester -3'-Deoxyadenosine, includes the following steps:
Step 1 weighs cordycepin bulk pharmaceutical chemicals and anhydrous pyridine according to certain solid-liquid ratio respectively, by load weighted cordycepin Bulk pharmaceutical chemicals are added in anhydrous pyridine, mixed solution are obtained after stirring and dissolving, for use；
Step 2, the mixed solution for obtaining step 1 are slowly added dropwise under conditions of nitrogen protection, magnetic force heating stirring The furoyl chloride of certain mass is reacted, and reaction process is monitored with thin-layer chromatography, and it is stand-by that reaction solution is obtained after reaction；
Step 3, the reaction solution for obtaining step 2 are evaporated under reduced pressure, and obtain paste product, for use；
Step 4 after dissolving the paste product that step 3 obtains with distilled water, is extracted with ethyl acetate 3 times, merges organic Phase solution, for use；
Step 5, the organic phase solution vacuum distillation for obtaining step 4 remove organic solvent, obtain solid powder mixture It is mixed with column chromatography silica gel, the method for dry method loading carries out column chromatography, obtains 5'- furoyl ester -3'-Deoxyadenosine.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, in step 1 cordycepin bulk pharmaceutical chemicals and The solid-liquid ratio of anhydrous pyridine is 1g:45~55ml.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, furoyl chloride and step in step 2 The mass ratio of cordycepin bulk pharmaceutical chemicals is 0.55~0.65:1 in rapid 1, is heated to be water-bath mode and heats, and heating temperature is 68~72 DEG C, 4.8~5.2h of reaction time.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, thin-layer chromatography solvent is in step 2 The mixed solvent of methanol and methylene chloride, wherein the volume ratio of methanol and methylene chloride is 1:10, is observed under uv analyzer thin Laminate, raw material point disappear, and reaction terminates.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, Rotary Evaporators are 80 in step 3 It is evaporated under reduced pressure at DEG C, 5~10min of distillation time.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, the distilled water being added in step 4 Temperature is 60 DEG C, and the volume ratio of volume and ethyl acetate that distilled water is added is 10ml:25~35ml.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, step 5 center pillar chromatography use solvent For methanol, methylene chloride mixed solvent, the volume ratio of the methanol and the methylene chloride is 1:15, and upper silicagel column is 2 × 75cm glass column, silica gel are 200~300 mesh column chromatography silica gels.
The 5'- furoyl ester-of the synthetic method preparation of 5'- furoyl ester -3'-Deoxyadenosine of the present invention 3'-Deoxyadenosine inhibits the application in cancer drug in preparation, and the cancer includes liver cancer.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, synthetic reaction formula are reaction equation (1) It is shown:
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, the 5'- furoyl ester-of synthesis The chemical structural formula of 3'-Deoxyadenosine is as follows:
Beneficial effects of the present invention are as follows:
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, yield are 50% or more.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention synthesizes described in cordycepin analog 5'- furoyl ester -3'-Deoxyadenosine, by infrared spectroscopy, nuclear magnetic resonance spectroscopy, carbon spectrum and mass spectrum to the 5'- furan Carbamoyl ester -3'-Deoxyadenosine structure of muttering carries out characterization confirmation；The compound that synthesis obtains is carried out with MTT colorimetric method external The measurement of anti-tumor activity.
The synthetic method of 5'- furoyl ester -3'-Deoxyadenosine of the present invention, carry out anti tumor activity in vitro into Row research is the further investigation of cordycepin analogue antitumor action and explores cordycepin analogue in oncotherapy The prospect of application aspect provides foundation, is clinical application based theoretical to provide new thinking for its drug development.
The 5'- furans first of the synthetic method synthesis of 5'- furoyl ester -3'-Deoxyadenosine of the present invention Acyl ester -3'-Deoxyadenosine, can be improved the drug action of cordycepin.
The suppression that 5'- furoyl ester -3'-Deoxyadenosine that the present invention synthesizes improves cordycepin to HepG-2 cell Production is used.3 '-desoxyadenossine is as comparison medicine, IC50Value is 19.18ug/ml.5'- furoyl ester -3'-Deoxyadenosine IC50Value is 8.891ug/ml.
Detailed description of the invention
Fig. 1 is 5'- furoyl ester -3'-Deoxyadenosine infrared absorption spectra of one method of specific embodiment preparation；
Fig. 2 is the infrared absorption spectra of 3'-Deoxyadenosine；
Fig. 3 is 5'- furoyl ester -3'-Deoxyadenosine nucleus magnetic hydrogen spectrum figure of one method of specific embodiment preparation；
Fig. 4 is 5'- furoyl ester -3'-Deoxyadenosine nuclear-magnetism carbon spectrogram of one method of specific embodiment preparation；
Fig. 5 is 5'- furoyl ester -3'-Deoxyadenosine mass spectrogram of one method of specific embodiment preparation；
Fig. 6 is that 5'- furoyl ester -3'-Deoxyadenosine MTT experiment of one method of specific embodiment preparation inhibits bent Line.
Specific embodiment
Specific embodiment 1:
A kind of synthetic method of 5'- furoyl ester -3'-Deoxyadenosine, includes the following steps:
Step 1 weighs cordycepin bulk pharmaceutical chemicals and anhydrous pyridine according to certain solid-liquid ratio respectively, by load weighted cordycepin Bulk pharmaceutical chemicals are added in anhydrous pyridine, mixed solution are obtained after stirring and dissolving, for use；
Step 2, the mixed solution for obtaining step 1 are slowly added dropwise under conditions of nitrogen protection, magnetic force heating stirring The furoyl chloride of certain mass is reacted, and reaction process is monitored with thin-layer chromatography, and it is stand-by that reaction solution is obtained after reaction；
Step 3, the reaction solution for obtaining step 2 are evaporated under reduced pressure, and obtain paste product, for use；
Step 4 after dissolving the paste product that step 3 obtains with distilled water, is extracted with ethyl acetate 3 times, merges organic Phase solution, for use；
Step 5, the organic phase solution vacuum distillation for obtaining step 4 remove organic solvent, obtain solid powder mixture It is mixed with column chromatography silica gel, the method for dry method loading carries out column chromatography, obtains 5'- furoyl ester -3'-Deoxyadenosine.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, cordycepin raw material in step 1 The solid-liquid ratio of medicine and anhydrous pyridine is 1g:50ml.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, furoyl chloride in step 2 It is 0.6:1 with the mass ratioes of cordycepin bulk pharmaceutical chemicals in step 1, is heated to be water-bath mode and heats, heating temperature is 70 DEG C, when reaction Between 5h.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, thin-layer chromatography is molten in step 2 Agent is the mixed solvent of methanol and methylene chloride, and wherein the volume ratio of methanol and methylene chloride is 1:10, is seen under uv analyzer Lamellae is examined, raw material point disappears, and reaction terminates.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, Rotary Evaporators in step 3 It is evaporated under reduced pressure at 80 DEG C, 5~10min of distillation time.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, the distillation being added in step 4 The temperature of water is 60 DEG C, and the volume ratio of volume and ethyl acetate that distilled water is added is 10ml:30ml.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, step 5 center pillar chromatography use exhibition Agent is opened as methanol, methylene chloride mixed solvent, the volume ratio of the methanol and the methylene chloride is 1:15, upper silicagel column For 2 × 75cm glass column, silica gel is 200 mesh column chromatography silica gels.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, when cordycepin bulk pharmaceutical chemicals are When 1g, the white solid powder 1.4369g that step 5 obtains finally obtains the 5'- furoyl ester -3'-Deoxyadenosine 0.695g, theory generate the 5'- furoyl ester -3'-Deoxyadenosine 1.38g, yield 50.4%.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, to the 5'- of synthesis Furoyl ester -3'-Deoxyadenosine carries out examination of infrared spectrum, as shown in Figure 1, Fig. 2 is the infrared absorption of 3'-Deoxyadenosine Spectrogram map as a comparison, it can be seen that 5'- furoyl ester -3'-Deoxyadenosine in Fig. 1 from the Spike controls of Fig. 1, Fig. 2 Characteristic peaks be 3486cm-1、3159cm-1、2934cm-1、2857cm-1、1736cm-1、1713cm-1、1662cm-1、1595cm-1、1479cm-1、1393cm-1、963cm-1, 729,636cm-1；The characteristic peaks of 3'-Deoxyadenosine (cordycepin) are in Fig. 2 3337cm-1、3141cm-1、2934cm-1、1671cm-1、1617cm-1、1479cm-1、1342cm-1、1304cm-1、829cm-1、 633cm-1；Wherein 3141cm-1For 5 hydroxyl characteristic absorption peaks, 3337cm-1The stretching vibration absworption peak of N-H is gone up for 6, 1341cm-1For the hydroxyl absorption peak of 5 primary alconols.Fig. 1 1341cmcm in Fig. 1 compared with Fig. 2-1Absorption peak disappears.Product exists 1736cmcm-1Place occurs compared with strong absworption peak, this is ester carbonyl group characteristic absorption peak, 1194cmcm-1Locating broad peak is the C on ester carbonyl group =O characteristic absorption peak.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, to the 5'- of synthesis Furoyl ester -3'-Deoxyadenosine carries out nucleus magnetic hydrogen spectrum analysis, test solvent DMSO, test frequency 10000Hz, test result As shown in figure 3, obtaining 13 signal peaks, it is respectively as follows:1HNMR (500MHz, DMSO-d6) δ 8.26 (1H, s, 2-H), 8.13 (1H, d, 8-H), the 7.98-6.70 (- CH=of 3H, d, 5 '), the 5.93 (- H of 1H, d, 1 '), the 5.77 (- H of 1H, d, 1 ') 4.69-4.24 (4H, Ddtd, 2 '-OH, 4 '-H, 5 '-CH2), the 2.06 (- CH of 2H, ddd, 3 '2)。
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, to the 5'- of synthesis Furoyl ester -3'-Deoxyadenosine carries out nuclear-magnetism carbon spectrum analysis test solvent DMSO, test frequency 29761.904Hz, test As a result as shown in figure 4, obtaining 15 signal peaks, it is respectively as follows: 13CNMR (126MHz, DMSO-d6) δ 158.16 (1C ,-COO), 156.52 (1C, 6-C), 153.10 (1C, 2-C), 149.47 (1C, 4-C), 148.27-143.97 (2C, 5 '-CH=), 139.31 (1C, 8-C), 119.44 (1C, 5-C), 119.15-112.85 (2C, 5 '-CH=), 91.22 (1C, 1 '-C), 77.87 (1C, 4 '- C), 74.81 (1C, 2 '-C), 65.95 (1C, 5 '-C), 35.17 (1C, 3 '-C).
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, to the 5'- of synthesis Furoyl ester -3'-Deoxyadenosine, is analyzed by mass spectrometry, and test results are shown in figure 5, and mass spectrometric measurement result compound is opposite Molecular weight is 346.1154, and compound predicted molecular weight is 345, and test result is consistent with prediction result.
Specific embodiment 2:
A kind of 5'- furoyl ester -3'-Deoxyadenosine of one synthetic method of specific embodiment preparation inhibits cancer in preparation Application in disease drug, the cancer include liver cancer.
Present embodiment 5'- furoyl ester -3'-Deoxyadenosine inhibits the application in cancer drug in preparation, described 5'- furoyl ester -3'-Deoxyadenosine carries out cell Proliferation detection, test method MTT test method:
The first step is the recovery of cell: after the cryopreservation tube that liquid nitrogen container takes out dress HepG2 cell, rapidly being put into cryopreservation tube It thaws rapidly for 37 DEG C into the water-bath having been warmed up, and constantly shakes, melt liquid in pipe rapidly.It is frozen after about 1min Liquid in pipe is completely dissolved, and the wiping of taking-up cotton ball soaked in alcohol freezes pipe outer wall, is placed into superclean bench, is sucked out with suction pipe thin Born of the same parents' suspension injects centrifuge tube and adds 10 times of culture solutions, and 1000rpm is centrifuged 5min after mixing.It inhales and abandons supernatant, add into centrifuge tube Enter 10mL culture solution, cell suspension is made in piping and druming.Cell count adjusts cell concentration with 3 × 104cell/mL.By cell suspension point It is packed into culture bottle, culture bottle is put into 37 DEG C of .5%CO2Culture in incubator, next day replace a culture solution.
Second step is the secondary culture of cell: Bel7402 HepG2: routine culture is containing 10% calf serum In mono- 1640 culture medium of RPMI, 37 DEG C are placed in, 5%C02In saturated humidity incubator, melt to its adherent growth to 80%-90% When conjunction, with PBS liquid scrubbing cell twice after, with 0.25% trypsin digestion and cell, microscopically observation waits for the big portion of cell Divide after being rounded, discard digestive juice, the RPMI-1640 culture solution 5mL of 10% calf serum is added in culture bottle, is filled repeatedly with suction pipe Divide piping and druming bottle wall, single cell suspension is made, further according to one bottle of biography two bottles or three bottles of principles, is added and contains 10% calf serum in right amount RPMI-1640 culture solution mix after be respectively charged into each bottle, set 37 DEG C, 5%C02Saturated humidity incubator culture.It is counted under mirror, Adjust cell concentration to 3 × 104A/mL.
Third step is solution preparation: PBS: accurately weighing KCL0.4g, NaCL16g, Na2HP0412H205.76g, KH2P040.4g adds ddH20 dissolution to be settled to 2L, adjusts the PH of solution within the scope of 7.2-7.4 with HCL, sterile with 0.22 μm Membrane filtration degerming, high pressure sterilization, 4 DEG C of refrigerators save.MTT: weighing MTT50mg, and 10mLPBS is added to be protected from light ultrasonic dissolution, 0.22 μ M membrane filtration degerming, 4 DEG C are kept in dark place.
4th step is IC50 measurement: cell is with 5 × 105The inoculum concentration of a/mL is inoculated in 96 well culture plates, 5%CO2, 37 DEG C After cultivating for 24 hours in incubator, each 10 μ L of drug of various concentration is added in every hole, makes the drug final concentration of preliminary screening be respectively 103.102.10 μ g/mL continues culture for 24 hours, and the drug concentration finally screened is respectively 100.200.400.600.800 μ g/ ML, 5, every hole parallel hole.Cell suspension is not added in zeroing hole, only plus contains 10% fetal calf serum RPMI-1640200 μ L, continues to cultivate 48h is separately added into 50 μ LMTT (thiazolyl blue) incubation 4h and discards culture medium, 150 μ LDMSO are added and shake up on plate shaker, The read plate at microplate reader 490nm calculates IC with analysis software SPSS according to the absorbance value measured50Value.
5th step is cell inhibitory rate measurement: the HepG2 cell in logarithmic growth phase is taken, 1000rpm is centrifuged 10min, Sedimentation cell concentration is adjusted to 1 × 10 with RPMI-1640 culture solution (containing 10% fetal calf serum)5cell·mL-1After cell suspension, By cell inoculation in 96 well culture plates.Every hole adds 100 μ L (1 × 10 of cell suspension4Cell), it is different to be then respectively adding concentration N- benzoyl cordycepin, N- thiophene-carboxamides cordycepin, N- amide cordycepin, 200 μ gmL of cordycepin-1Not drug containing Each 100 μ L of culture solution, 4, every hole parallel hole makes total volume up to 200 μ L.HepG2 cell suspension is not added in zeroing hole, only plus contains 10% fetal calf serum RPMI-1640200 μ L.Mix 37 DEG C of postposition, 5%CO2, cultivate 48h under 95% damp condition after, every hole adds Enter 5mgmL-120 μ L of MTTPBS liquid, continue under similarity condition to cultivate 4h, terminate culture.1000rpm is centrifuged 5min, then inhales The culture solution in cultivation plate hole is abandoned, 150 μ LDMSO are added in every hole, and 10min is shaken, makes to form formazan particle after completely dissolution, Microplate reader detects light absorption value.Selection measurement wavelength 490nm.Inhibitory rate of cell growth, test result such as table 1 are calculated by following formula It is shown:
Inhibitory rate of cell growth (%)=× 100% (3) (1- experimental port OD570/ control wells OD570)
Table 1MTT test comparison table
, it can be seen that 5'- furoyl ester -3'-Deoxyadenosine has inhibiting effect (P to HepG-2 cell from table 1 < 0.01), inhibiting rate 50%, inhibitory effect is as shown in Fig. 6, it can be seen that 5'- furoyl ester -3'- deoxidation from Fig. 6 Adenosine is to the increase that the inhibitory effect of HepG-2 cell is with administration concentration, and inhibiting effect is also increasingly stronger, when dense When degree reaches 8.891ug/ml, inhibitory effect reaches cell growth half and inhibits.
Specific embodiment 3:
A kind of synthetic method of 5'- furoyl ester -3'-Deoxyadenosine, includes the following steps:
Step 1 weighs cordycepin bulk pharmaceutical chemicals and anhydrous pyridine according to certain solid-liquid ratio respectively, by load weighted cordycepin Bulk pharmaceutical chemicals are added in anhydrous pyridine, mixed solution are obtained after stirring and dissolving, for use；
Step 2, the mixed solution for obtaining step 1 are slowly added dropwise under conditions of nitrogen protection, magnetic force heating stirring The furoyl chloride of certain mass is reacted, and reaction process is monitored with thin-layer chromatography, and it is stand-by that reaction solution is obtained after reaction；
Step 3, the reaction solution for obtaining step 2 are evaporated under reduced pressure, and obtain paste product, for use；
Step 4 after dissolving the paste product that step 3 obtains with distilled water, is extracted with ethyl acetate 3 times, merges organic Phase solution, for use；
Step 5, the organic phase solution vacuum distillation for obtaining step 4 remove organic solvent, obtain solid powder mixture It is mixed with column chromatography silica gel, the method for dry method loading carries out column chromatography, obtains 5'- furoyl ester -3'-Deoxyadenosine.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment, yield are 50% or more.
5'- furoyl ester -3'-Deoxyadenosine synthetic method described in present embodiment synthesizes cordycepin 5'- furoyl ester -3'-Deoxyadenosine described in analog passes through infrared spectroscopy, nuclear magnetic resonance spectroscopy, carbon spectrum and mass spectrum pair The 5'- furoyl ester -3'-Deoxyadenosine structure carries out characterization confirmation；The chemical combination that synthesis is obtained with MTT colorimetric method The measurement of object progress anti tumor activity in vitro.
5'- furoyl ester -3'-Deoxyadenosine synthetic method, is resisted in vitro described in present embodiment Tumor promotion is studied, and is further investigation and the exploration cordycepin analogue of cordycepin analogue antitumor action Prospect in terms of cancer therapeutic applications provides foundation and establishes to provide new thinking for its drug development for clinical application Theoretical basis.
Specific embodiment 4:
According to 5'- furoyl ester -3'-Deoxyadenosine synthetic method described in specific embodiment three, worm in step 1 The solid-liquid ratio of careless element bulk pharmaceutical chemicals and anhydrous pyridine is 1g:45~55ml.
Specific embodiment 5:
According to 5'- furoyl ester -3'-Deoxyadenosine synthetic method described in specific embodiment three, furan in step 2 The mass ratio of cordycepin bulk pharmaceutical chemicals is 0.55~0.65:1 in formyl chloride and the step 1 of muttering, and is heated to be water-bath mode and heats, heating temperature Degree is 68~72 DEG C, 4.8~5.2h of reaction time.
Specific embodiment 6:
It is thin in step 2 according to 5'- furoyl ester -3'-Deoxyadenosine synthetic method described in specific embodiment three Layer chromatography solvent be methanol and methylene chloride mixed solvent, wherein the volume ratio of methanol and methylene chloride be 1:10, ultraviolet point Lamellae is observed under analyzer, raw material point disappears, and reaction terminates.
Specific embodiment 7:
According to 5'- furoyl ester -3'-Deoxyadenosine synthetic method described in specific embodiment three, revolved in step 3 Turn evaporimeter to be evaporated under reduced pressure at 80 DEG C, 5~10min of distillation time.
Specific embodiment 8:
According to 5'- furoyl ester -3'-Deoxyadenosine synthetic method described in specific embodiment three, add in step 4 The temperature of the distilled water entered is 60 DEG C, and the volume ratio of volume and ethyl acetate that distilled water is added is 10ml:25~35ml.
Specific embodiment 9:
According to 5'- furoyl ester -3'-Deoxyadenosine synthetic method, step 5 center pillar described in specific embodiment three Chromatography is methanol, methylene chloride mixed solvent with solvent, and the volume ratio of the methanol and the methylene chloride is 1:15, Upper silicagel column is 2 × 75cm glass column, and silica gel is 200~300 mesh column chromatography silica gels.
Specific embodiment 10:
5'- furoyl ester -3'-Deoxyadenosine synthetic method system according to one of specific embodiment three-nine Standby 5'- furoyl ester -3'-Deoxyadenosine inhibits the application in cancer drug in preparation, and the cancer includes liver cancer.

Claims (8)

1. a kind of synthetic method of 5'- furoyl ester -3'-Deoxyadenosine, characterized by the following steps:
Step 1 weighs cordycepin bulk pharmaceutical chemicals and anhydrous pyridine according to certain solid-liquid ratio respectively, by load weighted cordycepin raw material Medicine is added in anhydrous pyridine, mixed solution is obtained after stirring and dissolving, for use；
Step 2, the mixed solution for obtaining step 1 are slowly added dropwise certain under conditions of nitrogen protection, magnetic force heating stirring The furoyl chloride of quality is reacted, and reaction process is monitored with thin-layer chromatography, and it is stand-by that reaction solution is obtained after reaction；
Step 3, the reaction solution for obtaining step 2 are evaporated under reduced pressure, and obtain paste product, for use；
Step 4 after dissolving the paste product that step 3 obtains with distilled water, is extracted with ethyl acetate 3 times, merges organic mix Liquid, for use；
Step 5, the organic phase solution vacuum distillation for obtaining step 4 remove organic solvent, obtain solid powder mixture and column Chromatographic silica gel mixes, and the method for dry method loading carries out column chromatography, obtains 5'- furoyl ester -3'-Deoxyadenosine.
2. the synthetic method of 5'- furoyl ester -3'-Deoxyadenosine according to claim 1, it is characterised in that: step 1 The solid-liquid ratio of middle cordycepin bulk pharmaceutical chemicals and anhydrous pyridine is 1g:45~55ml.
3. the synthetic method of 5'- furoyl ester -3'-Deoxyadenosine according to claim 1, it is characterised in that: step 2 The mass ratio of cordycepin bulk pharmaceutical chemicals is 0.55~0.65:1 in middle furoyl chloride and step 1, is heated to be water-bath mode and heats, adds Hot temperature is 68~72 DEG C, 4.8~5.2h of reaction time.
4. the synthetic method of 5'- furoyl ester -3'-Deoxyadenosine according to claim 1, it is characterised in that: step 2 Middle thin-layer chromatography solvent is the mixed solvent of methanol and methylene chloride, and wherein the volume ratio of methanol and methylene chloride is 1:10, purple Lamellae is observed under outer analysis instrument, raw material point disappears, and reaction terminates.
5. the synthetic method of 5'- furoyl ester -3'-Deoxyadenosine according to claim 1, it is characterised in that: step 3 Middle Rotary Evaporators are evaporated under reduced pressure at 80 DEG C, 5~10min of distillation time.
6. the synthetic method of 5'- furoyl ester -3'-Deoxyadenosine according to claim 1, it is characterised in that: step 4 The temperature of the distilled water of middle addition is 60 DEG C, and the volume ratio of volume and ethyl acetate that distilled water is added is 10ml:25~35ml.
7. the synthetic method of 5'- furoyl ester -3'-Deoxyadenosine according to claim 1, it is characterised in that: step 5 Center pillar chromatography is methanol, methylene chloride mixed solvent with solvent, and the volume ratio of the methanol and the methylene chloride is 1:15, upper silicagel column are 2 × 75cm glass column, and silica gel is 200~300 mesh column chromatography silica gels.
8. a kind of 5'- furoyl ester -3'-Deoxyadenosine of claim 1-7 synthetic method preparation inhibits cancer medicine in preparation Application in object, it is characterised in that: the cancer includes liver cancer.
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