CN112175032A - Rapid synthesis method of 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound - Google Patents
Rapid synthesis method of 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound Download PDFInfo
- Publication number
- CN112175032A CN112175032A CN202011239986.XA CN202011239986A CN112175032A CN 112175032 A CN112175032 A CN 112175032A CN 202011239986 A CN202011239986 A CN 202011239986A CN 112175032 A CN112175032 A CN 112175032A
- Authority
- CN
- China
- Prior art keywords
- compound
- reaction
- tert
- substituted
- deoxynucleoside
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
Abstract
The invention belongs to the technical field of chemical synthesis, and discloses a method for quickly synthesizing a 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound. Under the protection of nitrogen, reacting the 5-substituted deoxynucleoside compound with tert-butyldimethylsilyl chloride, and performing post-treatment after the reaction is finished to obtain a compound a; compound a in NaHCO3Under catalysis with P2S5And carrying out chemical reaction in diethanol dimethyl ether to finally obtain a compound b. The synthesis method has the advantages of short reaction time, single product, high reaction yield, few byproducts, simple post-treatment and the like, avoids using a pyridine solvent with high toxicity and malodor, avoids using a 1, 4-dioxane solvent with high boiling point, avoids using a Lawson reagent which is easy to deteriorate and has a large number of reaction byproducts, and simplifies the post-treatment column passing process.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and relates to a method for quickly synthesizing a 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound.
Background
Thiopyrimidine nucleoside is a promising photosensitizer, and can selectively kill faster proliferating cancer cells in synergy with UVA (Jiang leather, Luo Feng, Xudazao, et al. research on near ultraviolet light-assisted 4-thiodeoxythymidine anticancer effects [ J ] chemical evolution, 2016,28(8):1224-1237 ]. Thiopyrimidine nucleosides are structurally different from natural nucleosides in that they are obtained by sulfurizing the oxygen atom at the 4-position of a natural pyrimidine nucleoside and are significantly different from natural nucleosides in biological properties. Compared with natural nucleotide, the pyrimidine ring series nucleoside compound containing sulfhydryl group has anticancer activity and immunity enhancement effect (NIGMN SC, SAHARA GS, SHAMM HR. Indian Chem Soc, 1983, 60: 583-.
4-thio-deoxynucleoside analogs have been found to be very sensitive to ultraviolet light and are potentially useful as anti-tumor agents, particularly in combination with near ultraviolet light (UVA) for the treatment of skin cancer (Pridgon SW, Heer R, Taylor GABr. J. cancer 2011,104,1869.). Brady-dazzling and Karran et al (Massey M, Xu YZ, Karran p. curr. biol.2011,11,1142) propose a new photochemotherapeutic approach, i.e. ultraviolet light assisted 4-thiothymidine therapy. The therapy utilizes the characteristics that thiothymidine has a similar structure to natural thymidine and cancer cells rapidly replicate and grow in a human body, 4-thiothymidine analogues are incorporated into cancerated tissues, and DNA of the cancer cells is selectively damaged through the synergistic effect of UVA with a specific wavelength, so that the purpose of selectively killing the cancer cells is achieved (Jiang leather, Rongfen, Xudazhuang, and the like, near ultraviolet light assists in the research on the anti-cancer effect of 4-thiodeoxythymidine [ J ] chemical development, 2016,28(8):1224 1237 ].
Based on the unique biological properties of 4-thiodeoxynucleoside analogs, a large number of syntheses of 4-thiodeoxynucleosides have been reported, but most have used lawson's reagent or phosphorus pentasulfide (P)2S5) To synthesize 4-thiodeoxynucleoside analogs using Lawson's reagent or phosphorus pentasulfide (P)2S5) In the reaction process of the sulfurized deoxynucleoside, the reaction time is too long, the used reaction solvent has a strong taste and a high boiling point, and the sulfurized deoxynucleoside is difficult to remove by means of reduced pressure evaporation. In addition, when the thionization reaction is carried out using the lawson reagent, a large amount of black by-products are produced, and the post-treatment is difficult, and it is also difficult to obtain a pure substance by column purification.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound and a rapid synthesis method thereof. The synthesis method has the advantages of short reaction time (generally, the reaction is completed within 1 hour), high yield, no difficultly separated by-product and few by-products, only water washing is needed for post-treatment, dichloromethane is used for extraction, and reduced pressure evaporation is carried out to obtain the relatively pure 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound, and the relatively pure 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound can be rapidly separated by column chromatography.
The above purpose of the invention is realized by the following technical scheme:
a 5-substituted-4-thio-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound; having the structure of formula (b):
wherein X is CH3、H、F、Cl、Br、I。
The specific structural formula of the 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound is as follows:
wherein A is 4-thio-2 ', 3' -O-di-tert-butyldisilyl deoxythymidine, B is 4-thio-2 ', 3' -O-di-tert-butyldisilyl deoxyuridine, C is 4-thio-5-fluoro-2 ', 3' -O-di-tert-butyldisilyl deoxyuridine, D is 4-thio-5-chloro-2 ', 3' -O-di-tert-butyldisilyl deoxyuridine, E is 4-thio-5-bromo-2 ', 3' -O-di-tert-butyldisilyl deoxyuridine, and F is 4-thio-5-iodo-2 ', 3' -O-di-tert-butyldisilyl deoxyuridine.
The 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl nucleoside compoundA rapid synthesis method; taking deoxynucleoside as raw material and P2S5As a sulfurizing agent, NaHCO3Is used as a catalyst and undergoes chemical reaction in diethanol dimethyl ether to finally obtain a compound b shown as a general formula (b);
wherein X is CH3、H、F、Cl、Br、I。
Further, the rapid synthesis method of the 5-substituted-4-thio-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound comprises the following steps: under the protection of nitrogen, reacting a 5-substituted deoxynucleoside compound with tert-butyldimethylsilyl chloride (TBSCl), and performing post-treatment after the reaction to obtain a compound a shown in a general formula (a); the compound a is then reacted with P dissolved in diethanol dimethyl ether solvent2S5And NaHCO3And reacting to obtain a yellow solid b.
Further, the method for rapidly synthesizing the 5-substituted-4-thio-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound comprises the following specific steps:
s1, synthesis of a compound a: under the protection of nitrogen, 1 equivalent of 5-substituted deoxynucleoside compound and 3 equivalents of imidazole are dissolved in dichloromethane and stirred for 30 minutes in ice water bath (0 ℃); after 30 minutes, adding 2.5 equivalents of tert-butyldimethylsilyl chloride (TBSCl) into the reaction system, and stirring at room temperature for 1 hour; after TLC detection reaction is finished, quenching with water and extracting with dichloromethane; the organic phases were combined, washed with saturated NaCl and anhydrous NaSO4Drying, filtering, and evaporating the solvent under reduced pressure to obtain compound a as white solid, which is directly subjected to the next step S2 without purification;
s2, synthesis of a compound b: adding 1 equivalent of compound a into a solution of 2 equivalents of P2S5After being uniformly stirred, 4 equivalents of NaHCO are added into the solution of the diethanol dimethyl ether3The solid is added into the reaction system, and the reaction speed depends on CO2And (4) precipitating. The reaction was stirred further to 110 ℃ until the TLC detection reaction was complete. After the reaction is finished, the reaction is carried outPouring the solution into cold water, separating out yellow solid, filtering, washing with cold water, and collecting the product.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a rapid synthesis method for preparing the 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound. From the synthesis of the compounds a-b, using P2S5As sulfurizing agent, in NaHCO3Under catalysis with P2S5Formation of NaSPS2Characteristic of salts, NaSPS2Formation of SPS in reaction solution2-，SPS2-attack 4-carbonyl oxygen on pyrimidine ring of 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyloxynucleoside compound as nucleophilic reagent, and then synthesize target compound 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyloxynucleoside compound. The invention realizes the rapid vulcanization of the 4-oxygen atom of the 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound, which is different from the direct vulcanization method which is a common vulcanization means, the prior art usually uses vulcanization reagents such as Lawson reagent, phosphorus pentasulfide or thioacetic acid to directly vulcanize the 4-oxygen atom on the pyrimidine ring of the pyrimidine nucleoside compound, and the invention utilizes SPS2-the ion acts as a nucleophile to rapidly sulphurize the oxygen atom at the 4-position of the pyrimidine ring of the pyrimidine nucleoside compound, the reaction has the advantages of short reaction time (generally completed within 1 hour), specific product, high reaction yield, few by-products, easily soluble water by using the diethanol dimethyl ether and the inorganic salt in the post-treatment process, the 5-substituted-4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound has the characteristic of being insoluble in water and soluble in dichloromethane, and the post-treatment process of the high-boiling point diethanol dimethyl ether solvent is simplified.
Drawings
FIG. 1 shows Compound a of example 1 of the present invention1Nuclear magnetic characterization map of。
FIG. 2 shows Compound b of example 1 of the present invention1The nuclear magnetism characterization map of (1).
Detailed Description
The invention is described in more detail below with reference to specific examples, without limiting the scope of the invention. Unless otherwise specified, the experimental methods adopted by the invention are all conventional methods, and experimental equipment, materials, reagents and the like used in the experimental method can be obtained from commercial sources.
Example 1
4-sulfur-2 ', 3' -O-di-tert-butyldisilyl deoxythymidine with the structural formula of (b)1) As shown in the drawings, the above-described,
s1. Compound a1The synthesis of (2): deoxythymidine (3g) and imidazole (2.52g) were dissolved in dichloromethane (20ml) under nitrogen, and stirred for 30 minutes in an ice-water bath (0 ℃). After 30 minutes, t-butyldimethylsilyl chloride (TBSCl) (4.65g) was added to the reaction system, and the mixture was stirred at room temperature for 1 hour (25 ℃ C. -30 ℃ C.). After the TLC detection reaction, the reaction mixture was quenched with water and extracted with dichloromethane. The organic phases were combined, washed with saturated NaCl and anhydrous NaSO4Drying, filtering, and vacuum evaporating to remove solvent to obtain compound a1As a white solid, 5.8g, yield 99%, the next step S2 was carried out without purification.1H NMR(CDCl3,500MHz):8.11(s,1H),7.48(s,1H),6.34(t,J＝6.7Hz,1H),4.42–4.36(m,1H),3.95–3.72(m,3H),2.27–2.19(m,1H),2.05–1.96(m,1H),1.92(s,3H),0.91(d,J＝17.9Hz,18H),0.14–0.04(m,12H)。
S2. Compound b1The synthesis of (2): 5.47g P2S5After sufficiently dissolving the compound in 24.64ml of diethanol dimethyl ether, the compound a prepared as described above was added1(5.8g) was put into the reaction solution and dissolved sufficiently, and solid NaHCO was added3(4.14g), NaHCO was added3Then, the gas is rapidly generated, and the reaction speed is determined by CO2The reaction solution was further stirred to 110 ℃ until the precipitation rate was reachedNo raw material a can be detected by TLC1Until now. After the reaction is finished, adding cold water into the reaction liquid to separate out a large amount of yellow solid, and filtering to obtain a compound b15.52g, 92% yield, the more pure compound was isolated by column chromatography flash (TLC: petroleum ether: ethyl acetate (V: V): 5: 1).1H NMR(CDCl3,500MHz):9.39(s,1H),7.51(s,1H),6.21(t,J＝6.7Hz,1H),4.34(s,1H),3.91(s,1H),3.86–3.65(m,2H),2.29–2.20(m,1H),2.04(s,3H),1.95(dt,J＝13.2,6.8Hz,1H),0.85(d,J＝15.1Hz,18H),0.04(d,J＝15.7Hz,12H)。
Example 2
4-thio-2 ', 3' -O-di-tert-butyldisilyl deoxyuridine, the structural formula of which is shown as the general formula (b)2) As shown in the drawings, the above-described,
s1. Compound a2The synthesis of (2): deoxyuridine (5g) and imidazole (4.49g) were dissolved in dichloromethane (34ml) under nitrogen protection, and stirred for 30 minutes under an ice-water bath (0 ℃). After 30 minutes, t-butyldimethylsilyl chloride (TBSCl) (8.3g) was added to the reaction system, and the mixture was stirred at room temperature for 1 hour (25 ℃ C. -30 ℃ C.). After the TLC detection reaction, the reaction mixture was quenched with water and extracted with dichloromethane. The organic phases were combined, washed with saturated NaCl and anhydrous NaSO4Drying, filtering, and vacuum evaporating to remove solvent to obtain compound a2As a white solid, 9.9g, yield 99%, the next step S2 was carried out without purification.1H NMR(CDCl3,500MHz):8.72(s,1H),7.95–7.87(m,1H),6.30(t,J＝6.1Hz,1H),5.69(d,J＝8.1Hz,1H),4.41(dd,J＝6.0,3.6Hz,1H),3.83(dd,J＝73.6,11.5Hz,3H),2.32(dt,J＝10.8,5.0Hz,1H),2.07(dt,J＝12.7,5.8Hz,1H),0.91(d,J＝15.0Hz,18H),0.09(d,J＝15.3Hz,12H)。
S2. Compound b2The synthesis of (2): mixing 4.87g P2S5After sufficiently dissolving in 21.89ml of diethanol dimethyl ether, compound a prepared as described above was added2(5g) Adding into the reaction solution, dissolving completely, adding solid NaHCO3(3.68g), NaHCO was added3Then, the gas is rapidly generated, and the reaction speed is determined by CO2The reaction solution was further stirred to 110 ℃ until the starting material a was not detected by TLC2Until now. After the reaction is finished, adding cold water into the reaction liquid to separate out a large amount of yellow solid, and filtering to obtain a compound b24.65g, 90% yield, the more pure compound was isolated by column chromatography flash (TLC: petroleum ether: ethyl acetate (V: V) ═ 5: 1).1H NMR(CDCl3,500MHz):9.58(s,1H),7.81(s,1H),6.42–6.32(m,1H),6.23(q,J＝6.0,4.3Hz,1H),3.96–3.71(m,3H),2.52(d,J＝4.7Hz,1H),2.35(h,J＝4.8Hz,1H),2.12–2.03(m,1H),0.90(d,J＝15.6Hz,18H),0.09(d,J＝13.9Hz,12H)。
The embodiments described above are merely preferred embodiments of the invention, rather than all possible embodiments of the invention. Any obvious modifications to the above would be obvious to those of ordinary skill in the art, but would not bring the invention so modified beyond the spirit and scope of the present invention.
Claims (3)
1. A5-substituted-4-thio-2 ', 3' -O-di-tert-butyldisilyl deoxynucleoside compound characterized by having a structure of the general formula (b):
wherein X is CH3、H、F、Cl、Br、I。
2. The method for synthesizing a 5-substituted-4-thio-2 ', 3' -O-di-tert-butyldimethylsilyl deoxynucleoside as claimed in claim 1, wherein the deoxynucleoside is used as a raw material, P is used as a stabilizer2S5As a sulfurizing agent, NaHCO3Is used as a catalyst and undergoes chemical reaction in diethanol dimethyl ether to finally obtain a compound b shown as a general formula (b);
wherein X is CH3、H、F、Cl、Br、I；
The synthesis steps are as follows: under the protection of nitrogen, reacting the 5-substituted deoxynucleoside compound with tert-butyldimethylsilyl chloride, and after the reaction is finished, carrying out post-treatment to obtain a compound a shown in a general formula (a); compound a in NaHCO3Under catalysis with P2S5And carrying out chemical reaction in diethanol dimethyl ether to finally obtain a compound b.
3. The method for synthesizing a 5-substituted-4-thio-2 ', 3' -O-di-tert-butyldimethylsilyl deoxynucleoside compound according to claim 2, wherein the synthesizing step comprises:
s1, synthesis of a compound a: under nitrogen protection, 1 equivalent of 5-substituted deoxynucleoside compound and 3 equivalents of imidazole were dissolved in dichloromethane under ice-water bath: stirring for 30 minutes at 0 ℃; after 30 minutes, adding 2.5 equivalents of tert-butyldimethylsilyl chloride into the reaction system, and stirring for 1 hour at room temperature; after TLC detection reaction is finished, quenching with water and extracting with dichloromethane; the organic phases were combined, washed with saturated NaCl and anhydrous NaSO4Drying, filtering, and evaporating the solvent under reduced pressure to obtain compound a as white solid, which is directly subjected to the next step S2 without purification;
s2, synthesis of a compound b: adding 1 equivalent of compound a into a solution of 2 equivalents of P2S5After being uniformly stirred, 4 equivalents of NaHCO are added into the solution of the diethanol dimethyl ether3The solid is added into the reaction system, and the reaction speed depends on CO2Precipitation of (2); continuously stirring the reaction solution to 110 ℃ until the TLC detection reaction is finished; after the reaction is finished, pouring the reaction liquid into cold water, separating out yellow solid, filtering and separating, washing with cold water, and collecting the product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011239986.XA CN112175032B (en) | 2020-11-09 | 2020-11-09 | Rapid synthesis method of 5-substituted-4-sulfur-2 ',3' -O-di-tert-butyldisilyl deoxynucleoside compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011239986.XA CN112175032B (en) | 2020-11-09 | 2020-11-09 | Rapid synthesis method of 5-substituted-4-sulfur-2 ',3' -O-di-tert-butyldisilyl deoxynucleoside compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112175032A true CN112175032A (en) | 2021-01-05 |
| CN112175032B CN112175032B (en) | 2022-11-04 |
Family
ID=73917899
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011239986.XA Active CN112175032B (en) | 2020-11-09 | 2020-11-09 | Rapid synthesis method of 5-substituted-4-sulfur-2 ',3' -O-di-tert-butyldisilyl deoxynucleoside compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112175032B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675389A (en) * | 2011-03-08 | 2012-09-19 | 大连大学 | 5-iodine-4-sulfur-2'-deoxyuridine, and derivatives and synthetic method thereof |
| CN102718822A (en) * | 2012-05-18 | 2012-10-10 | 大连大学 | Synthetic method of 4-sulfur thymidine and analogues of 4-sulfur thymidine under microwave irradiation |
| CN110105416A (en) * | 2019-06-17 | 2019-08-09 | 大连大学 | A kind of 4-S-5-Br-2 ', 3 ', 5 '-O- triacetyl uridine synthetic methods |
| CN110204584A (en) * | 2019-06-17 | 2019-09-06 | 大连大学 | A kind of 4-S-2 ', 3 ', 5 '-O- triacetyl uridine synthetic methods |
-
2020
- 2020-11-09 CN CN202011239986.XA patent/CN112175032B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675389A (en) * | 2011-03-08 | 2012-09-19 | 大连大学 | 5-iodine-4-sulfur-2'-deoxyuridine, and derivatives and synthetic method thereof |
| CN102718822A (en) * | 2012-05-18 | 2012-10-10 | 大连大学 | Synthetic method of 4-sulfur thymidine and analogues of 4-sulfur thymidine under microwave irradiation |
| CN110105416A (en) * | 2019-06-17 | 2019-08-09 | 大连大学 | A kind of 4-S-5-Br-2 ', 3 ', 5 '-O- triacetyl uridine synthetic methods |
| CN110204584A (en) * | 2019-06-17 | 2019-09-06 | 大连大学 | A kind of 4-S-2 ', 3 ', 5 '-O- triacetyl uridine synthetic methods |
Non-Patent Citations (6)
| Title |
|---|
| PETER C. TLATELPA等: "Stability of pyrimidine N-glycosydic bonds in the presence of Lawesson’s reagents: revisit of 2-thiolation of pyrimidine nucleosides", 《TETRAHEDRON LETTERS》 * |
| WING L. SUNG: "Chemical Conversion of Uridine into 4-Thiouridine via the 4-(1,2,4-Triazol-l -yl)pyrimidin-2(1 H)-one Intermediate", 《J. CHEM. SOC., CHEM. COMMUN.》 * |
| YAO-ZHONG XU等: "Simple Synthesis of 4-Thiothymidine, 4-Thiouridine and 6-Thio-2’-deoxyguanosine", 《TETRAHEDRON LETTERS》 * |
| 银鸿雁 等: "4-硫胸苷的合成及其与人血清白蛋白的相互作用", 《发光学报》 * |
| 银鸿雁 等: "荧光素标记5-溴-4-硫-2′-脱氧尿苷合成及荧光光谱研究", 《分子科学学报》 * |
| 霍书华 等: "４-硫胸苷的微波合成及光谱性质研究", 《分子科学学报》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112175032B (en) | 2022-11-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101180695B1 (en) | Methods for Preparing high purity chlorophyll and Chlorin e6 from Chlorophyll extracts | |
| CN102417491B (en) | Method for preparing cabazitaxel by taking 10-deacetylate-baccatin III as raw material | |
| EP1916251A1 (en) | Erianin salts, their preparation methods and pharmaceutical compositions containing the same | |
| EP3055295A1 (en) | Synthesis of 1-alkyl-2-amino-imidazol-5-carboxylic acid ester via calpha-substituted n-alkyl-glycine ester derivatives | |
| CN111253448A (en) | Preparation method and purification method of β -nicotinamide mononucleotide | |
| CN113683651A (en) | Preparation method of GalNAc intermediate | |
| CN105481946B (en) | The conjugate and its preparation method and purposes of 5-ALA and 3- pyridone -4- ketone | |
| WO2022017317A1 (en) | Method for large-scale synthesis of tetrodotoxin | |
| CN112175032B (en) | Rapid synthesis method of 5-substituted-4-sulfur-2 ',3' -O-di-tert-butyldisilyl deoxynucleoside compound | |
| CN106046105A (en) | Preparation method and application of glycyrrhetinic acid, ferulic acid and selenomethionine ternary compound | |
| CN106831826B (en) | A kind of method that eldisine is prepared from catharanthus roseus | |
| CN113563401A (en) | Novel cordycepin alkanamide derivative and preparation method and application thereof | |
| CN109134331A (en) | The synthetic method of azithromycin genotoxicity impurity | |
| CN110452134B (en) | Nitric oxide donor small molecule and preparation and application thereof | |
| CN112225760B (en) | Synthesis method of 5-substituted-4-sulfur-2 ',3',5' -O-tri-tert-butyldimethylsilyl nucleoside compound | |
| CN104592253B (en) | Novel synthesis method of temsirolimus | |
| CN112239484A (en) | Synthesis method of 5-halo-4-thio-2 ', 3' -O-di-tert-butyldimethylsilyl nucleoside compound | |
| CN114380888B (en) | Difluoro substituted romidepsin analogue, preparation method and application thereof | |
| CN113773324B (en) | Synthesis and preparation process of antitumor drug CFI-402257 | |
| CN113402578B (en) | Diosgenin derivative and preparation method and medical application thereof | |
| CN113683539B (en) | Synthesis method of polyketone intermediate | |
| CA3074247A1 (en) | Process for the preparation of ixazomib citrate | |
| CN111944000A (en) | 5-substituted-2, 4-dithio-2 ', 3' -O-di-tert-butyldisilyl nucleoside compound and synthetic method thereof | |
| CN114213490B (en) | Tricyclic nucleotide analogues and synthetic method and application thereof | |
| CN113512066B (en) | Sorafenib-ruthenium complex and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |