CN109336921B - DNA base analogue, application and synthetic method thereof - Google Patents
DNA base analogue, application and synthetic method thereof Download PDFInfo
- Publication number
- CN109336921B CN109336921B CN201810968214.6A CN201810968214A CN109336921B CN 109336921 B CN109336921 B CN 109336921B CN 201810968214 A CN201810968214 A CN 201810968214A CN 109336921 B CN109336921 B CN 109336921B
- Authority
- CN
- China
- Prior art keywords
- azo
- dna base
- dna
- base analog
- producing
- 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.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
- C07F9/2404—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Abstract
The invention relates to a DNA base analogue, application and a synthetic method thereof, wherein the structural formula of the DNA base analogue is shown as follows:
the DNA base analog can be embedded and modified into a DNA sequence by utilizing a DNA synthesizer. The change of cis-trans isomerism of azobenzene group embedded in the sequence in the visible light range (green light and blue light) is utilized to perform biological reactions such as noninvasive and reversible regulation of DNA hybridization and further regulation of related enzyme activity. The invention has the advantages of simple synthesis method, short time, low cost, high light regulation and control efficiency and the like, can regulate and control the cis-trans isomer in the visible light range, and has wide application prospect in the aspect of regulating and controlling some biological enzymes.
Description
Technical Field
The invention relates to a DNA basic group analogue, an application and a synthetic method thereof.
Background
The azobenzene compound is a compound with two ends of an azo group connected with a phenyl group. The unmodified azobenzene molecules exhibit strong pi-pi transitions in the UV region and weaker n-pi transitions in the visible region. The azobenzene compound has trans isomer and cis isomer, wherein the trans isomer has a planar structure, and the cis isomer has a non-planar structure. In general, the trans-isomer is relatively stable and can be converted into the cis-isomer under the condition of ultraviolet irradiation; on the contrary, under the irradiation of visible light or under the heating condition, the cis-isomer which is not thermodynamically stable is converted into the trans-isomer which is stable. The optical regulation and control performance of the cis-trans isomer of the azobenzene molecule is a hotspot of biological analysis and research.
Azobenzene molecules have a very large conjugated pi system and a large amount of electron cloud accumulation. After the azobenzene molecules are embedded into the DNA chain, the DNA embedded with the azobenzene can be well hybridized with complementary DNA thereof through the accumulation of electron clouds on the benzene ring and the electron clouds of the DNA base. When the azobenzene molecule is irradiated by ultraviolet light, the azobenzene molecule is converted from a trans isomer to a cis isomer, the configuration change of the azobenzene molecule destroys the non-covalent action of the azobenzene molecule and bases, the hybridization between DNA bases is destroyed, and finally, a hybridized DNA chain is melted. When the double-stranded DNA is irradiated by visible light, the azobenzene molecules are changed from cis-isomer to trans-isomer, and the double-stranded DNA is hybridized again. This hybridization and melting of the DNA can be achieved by controlling the light conditions. Compared with other regulation and control modes, the regulation and control mode has the advantages of simplicity, rapidness, high space-time resolution, non-invasiveness and the like. Has very wide application prospect for the light-controlled nuclease-related reaction system.
However, the conventional azobenzene molecule requires ultraviolet light as a light source due to the light regulation condition, and the ultraviolet light has great damage to a biological system, so that not only protein is denatured, but also nucleic acid is cleaved and the like.
Disclosure of Invention
The invention aims to provide a DNA base analogue with visible light controlled cis-trans isomerism and a synthesis method thereof. Wherein, the structural formula of the DNA base analogue is shown as the following,
the DNA base analogue synthesized by the method can be conveniently and efficiently embedded into a DNA chain by using a DNA synthesizer, and generates a cis-isomer after being irradiated by green light (515-535 nm) to destroy DNA hybridization; and then the trans-isomer conformation is returned after the irradiation of blue light (445-465 nm), and the DNA hybridization is recovered. The azobenzene DNA base analog designed by the invention can be embedded into any position in a DNA chain, and the light regulation and control effect on DNA hybridization in a visible light region is optimally realized through the design of the number of the embedded azobenzene molecules and the embedding position, so that the related biological reaction is effectively subjected to light regulation and control.
Preferably, the synthetic route of the DNA base analogues of the present invention is preferably as follows:
DNA base analogs were synthesized on the basis of tetramethoxyazobenzene carboxylic acid analogs. Connecting D-threitol by using Dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) to catalyze amide reaction to form an intermediate product AZO-02; on the basis of the intermediate AZO-02, introducing 4-4' -dimethoxytriphenylchloromethane, and taking pyridine and dichloromethane as solvents to obtain the intermediate AZO-03 under the catalytic action of 4-Dimethylaminopyridine (DMAP). 2-cyanoethyl N, N-diisopropyl phosphoramidite chloride is introduced on the basis of an intermediate AZO-03. Taking N, N-diisopropylethylamine as an alkali and a catalyst and dichloromethane as a solvent, and obtaining a final product AZO-04 under the anhydrous and anaerobic reaction conditions. The synthetic route is as follows:
preferably, in step one, the intermediate product with two hydroxyl groups is synthesized by introducing D-threoninol as a raw material on the basis of an azobenzene carboxylic acid analog (AZO-01) as a skeleton. The intermediate product AZO-02 is obtained by forming amido bond by the condensation of N, N' -Dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt).
Preferably, step one comprises: AZO-01, D-threitol, dicyclohexylcarbodiimide, 1-hydroxybenzotriazole and 4-dimethylaminopyridine are mixed according to a molar ratio of 1-5:1-5:1-5:1-5:0.1-1, and an appropriate amount of anhydrous THF and methanol are added into the mixture to be stirred at room temperature for reaction overnight; after the reaction is finished, filtering to remove the precipitate to obtain AZO-02.
Preferably, in the second step, on the basis of the intermediate AZO-02, 4' -dimethoxytriphenylchloromethane is introduced as a raw material, and the intermediate AZO-03 is obtained under the catalytic action of 4-Dimethylaminopyridine (DMAP) by taking pyridine and dichloromethane as solvents.
Preferably, step two includes: mixing AZO-02 and 4-dimethylaminopyridine in a molar ratio of 1:0.01-0.1, removing air in a container, and adding 1-10 times of pyridine in volume; obtaining a first solution;
4,4' -dimethoxytrityl chloride with the molar ratio of 1-2 to AZO-2 is put in another container, air is pumped out and removed, and then 1-10 times of volume of dichloromethane is added to obtain a second solution; dropwise adding the second solution into the first solution, and stirring at room temperature in a dark place for reaction overnight; after the reaction is finished, extracting by using water and ethyl acetate, reserving the organic phase, drying, and removing the organic solvent to obtain the AZO-03 product.
Preferably, step three, the raw material 2-cyanoethyl N, N-diisopropyl phosphoramidite chloride is introduced on the basis of the intermediate AZO-03; taking N, N-diisopropylethylamine as an alkali and a catalyst and dichloromethane as a solvent, and obtaining a final product AZO-04 under the anhydrous and anaerobic reaction conditions.
Preferably, in step three: adding AZO-03 into a container, and adding 1-20 times of dichloromethane in volume under the protection of nitrogen; under the condition of ice-water bath, dropwise adding 2-10 times of mol ratio of N, N-diisopropylethylamine and 0.5-2 times of mol ratio of 2-cyanoethyl N, N-diisopropylphosphoramidite, and reacting for 2-4 h in ice bath to obtain AZO-4.
The invention has the following advantages:
1. the synthetic raw materials are cheap, and the steps are simple and feasible;
2. after the molecules are embedded into a DNA chain, the cis-trans isomer of the azobenzene can be regulated and controlled by green light and blue light, and then the DNA hybridization and melting are regulated and controlled; the purple light is not needed, and the damage of the purple light to the biological system is avoided.
3. Can be embedded into any position of the DNA sequence by using a DNA synthesizer according to requirements;
4. the R position of the azobenzene embedded in the method can be-H, -OCH3，-CH3，-SCH3Etc. without affecting its light regulating effect on the inserted DNA.
Drawings
FIG. 1 shows AZO-04 as the final product1H NMR spectrum.
FIG. 2 is a diagram of AZO-04 as a final product31P NMR spectrum. In FIG. 2, 147ppm and 148ppm are characteristic peaks of phosphoramidite, and 14ppm is a characteristic peak of a by-product.
FIG. 3 shows the result of HPLC purification of DNA modified with azobenzene base analogue, wherein ① shows the absorption peak at 260nm and ② shows the absorption peak at 490nm (azobenzene molecule).
FIG. 4 shows green light (515) at 535nm,25mW/cm after different periods of time for DNA modified with azobenzene base analogues2) And (3) representing the irradiation time of 0min, 1.5min,3min,5min,10min,15min,30min and 60min in sequence by ① - ⑥, and gradually increasing the cis (%) content by calculating the integral area, so that the better green light irradiation time is 30 min.
FIG. 5 shows the DNA modified with azobenzene base analog after 30min of green light irradiation and then different periods of blue light (445-465nm,25 mW/cm)2) And (3) representing the irradiation time by ① - ④ as 0min, 2.5min,5min and 7.5min in sequence, and gradually reducing the cis (%) content by calculating the integral area, so that the preferable blue light irradiation time is 5 min.
FIG. 6 shows the modification of the DNA with azobenzene base analog by green light irradiation (515) 535nm,25mW/cm230min), the concentration of the cis conformation gradually decreased over time. According to ln [ cis ]]The slope obtained by plotting the time is the apparent rate of conversion K of the cis conformation to the trans conformationobsThen according to τ1/2＝ln 2/KobsAnd further get smoothHalf-life of the conversion of formula (I) to trans1/2＝46.2h。
Detailed Description
With R ═ OCH3For example, the synthetic route is as follows
1. The product AZO-02 is synthesized by the following synthetic route:
a round-bottomed flask was charged with AZO-01(390mg,1.0mmol), D-threoninol (106mg,1.0mmol), dicyclohexylcarbodiimide (DCC,247mg,1.2mmol), 1-hydroxybenzotriazole (HOBT,162mg,1.2mmol) and 4-dimethylaminopyridine (DMAP,24mg,0.2mmol), and an appropriate amount of anhydrous tetrahydrofuran and methanol were added thereto, and the reaction was stirred at room temperature overnight. After the reaction is finished, filtering to remove the precipitate, separating and purifying the crude product by using a silica gel chromatographic column, and characterizing by nuclear magnetism and mass spectrum.1H NMR(500MHz,CDCl3)δ＝6.97(s,2H),6.20(s,2H),4.24(m,2H),4.22(m,2H),3.88(s,3H),3.86(s,6H),3.72(s,6H),1.23(d,3H).ESI-MS Calculated for C22H30N3O8:464.2([M+H]+),found:464.8。
2. The product AZO-03 is synthesized by the following synthetic route:
a round bottom flask was charged with AZO-02(463mg,1.0mmol) and 4-dimethylaminopyridine (DMAP, 6.1mg,0.05mmol) and air purged, after which 2mL pyridine (pyridine) was added. 4,4' -Dimethoxytrityl chloride (DMT-Cl,339mg,1.0mmol) was weighed into another small round bottom flask, air was removed by suction, and 2mL of Dichloromethane (DCM) were added. Then, the DMT-Cl solution is dropwise added into the AZO-02 solution, and the mixture is stirred at room temperature in the dark for reaction overnight. After the reaction is finished, the reaction product is added with water and ethyl acetateExtracting, retaining organic phase, and adding anhydrous Na2SO4Drying, removing the organic solvent, separating and purifying the crude product by using a silica gel chromatographic column, and characterizing by nuclear magnetism and mass spectrum.1H NMR(500MHz,CDCl3)δ＝7.40(m,2H),7.29(m,5H),7.19(m,2H),7.11(s,2H),6.89(d,1H),6.80(m,4H),6.22(s,2H),4.20(m,1H),3.86(m,15H),3.76(d,6H),3.55(dd,1H),3.35(dd,1H),3.22(d,1H),1.21(d,3H).ESI-MS Calculated for C43H47N3O10:766.3([M+H]+),found:766.3。
3. The synthetic product AZO-04 is synthesized by the following synthetic route:
a round bottom flask was charged with AZO-03(765mg,1.0mmol) and 5mL of dichloromethane were added under nitrogen. Under the condition of ice-water bath, N-diisopropylethylamine (DIPEA,516mg and 4mmol) and 2-cyanoethyl N, N-diisopropyl chlorophosphite amide (237mg and 1.0mmol) are added dropwise, the mixture reacts for 2-4 h in ice bath, and is separated and purified by a silica gel chromatographic column and characterized by nuclear magnetism and mass spectrum, as shown in figures 1 and 2.1H NMR(500MHz,CDCl3)δ＝7.43(m,2H),7.31(d,4H),7.28(m,1H),7.22(m,1H),7.09(s,1H),7.05(s,1H),6.81(m,5H),6.22(s,2H),4.48(m,1H),4.38(m,1H),3.86(m,8H),3.83(m,6H),3.77(s,6H),3.53(m,4H),1.28(m,6H),1.13(m,12H),1.01(d,2H).ESI-MS Calculated for C52H65N5O11P:966.4([M+H]+),found:966.7。
4. And (3) applying the final product AZO-04 to a DNA synthesizer for synthesis.
A DNA oligonucleotide with a product AZO-04 is designed and synthesized, and the sequence is as follows: 5 '-GGT ATC X GCCTAA-3', wherein X is the product AZO-04, and the sequence is named mAZO-DNA. The product AZO-04 was inserted using a conventional DNA synthesis procedure, with only the coupling time being extended to 900 s. After the synthesis is finished, the DNA sequence is firstly cut off from the solid phase carrier CPG by methylamine/ammonia water (v/v,1/1), then methylamine/ammonia water is extracted, dissolved by 0.1mol/L triethylamine acetate (TEAA), and separated and purified by HPLC after passing through a membrane, as shown in figure 3.
5. HPLC characterization experiments with green light illumination control at different times.
6 μ L of 10 μ M mAZO-DNA (PBS buffer: 100mM NaCl,100mM phosphate, 5mM MgCl)2pH 7.4) at 25mW/cm2Respectively irradiating the raw materials for different times (0,5min,10min,15min,30min and 60min) under the condition of green light (515 nm-535 nm) of power, and then respectively carrying out HPLC analysis and characterization, wherein the results are shown in figure 4.
6. HPLC characterization experiments with blue light illumination control at different times.
4 of 50. mu.L of 10. mu.M mAZO-DNA (PBS buffer: 100mM NaCl,100mM phosphate, 5mM MgCl)2pH 7.4) sample, at first 25mW/cm2Irradiating for 30min under the condition of green light with power, and then, after different time (0,2.5min,5min,7.5min), blue light (445 nm-465 nm,25 mW/cm)2Power) and then separately characterized by HPLC analysis, the results are shown in fig. 5.
7. Calculation of half-life of the cis-to-trans conversion of azobenzene embedded in DNA.
8 pieces of 50. mu.L of 10. mu.M mAZO-DNA (PBS buffer: 100mM NaCl,100mM phosphate, 5mM MgCl)2pH 7.4) at 25mW/cm2Irradiating for 30min under the condition of green light with power, then respectively carrying out HPLC characterization at different time points after the illumination is finished, and obtaining the half-life of the cis-trans conversion of the azobenzene embedded in the DNA by statistics and calculation of peak areas, as shown in FIG. 6.
Claims (10)
- A DNA base analog having the ability to undergo cis and trans allosteric transformations under the irradiation of green and blue light, respectively, the structural formula of which is as follows:
- 2. use of a DNA base analogue according to claim 1 for the regulation of DNA hybridization and melting.
- 3. The method of using a DNA base analog according to claim 1, wherein the cis isomer is generated by green light irradiation; blue light irradiation, return to the trans isomer conformation.
- A method for preparing DNA base analogues, comprising the following synthetic steps:
- 5. the method for producing a DNA base analog according to claim 4, wherein:step one, introducing a raw material D-threoninol as a skeleton on the basis of an azobenzene carboxylic acid analogue to synthesize an intermediate product with two hydroxyl groups; the condensation reaction of N, N' -dicyclohexylcarbodiimide and 1-hydroxybenzotriazole is used for forming amido bond, and an intermediate product AZO-02 is obtained.
- 6. The method for producing a DNA base analog according to claim 4, wherein: the first step comprises the following steps: AZO-01, D-threitol, dicyclohexylcarbodiimide, 1-hydroxybenzotriazole and 4-dimethylaminopyridine are mixed according to a molar ratio of 1-5:1-5:1-5:1-5:0.1-1, and an appropriate amount of anhydrous THF and methanol are added into the mixture to be stirred at room temperature for reaction overnight; after the reaction is finished, filtering to remove the precipitate to obtain AZO-02.
- 7. The method for producing a DNA base analog according to claim 4, wherein: and step two, introducing a raw material of 4,4' -dimethoxy triphenylchloromethane on the basis of the intermediate product AZO-02, and obtaining the intermediate product AZO-03 under the catalytic action of 4-dimethylamino pyridine by taking pyridine and dichloromethane as solvents.
- 8. The method for producing a DNA base analog according to claim 7, wherein: the second step comprises the following steps: mixing AZO-02 and 4-dimethylaminopyridine in a molar ratio of 1:0.01-0.1, removing air in a container, and adding 1-10 times of pyridine in volume; obtaining a first solution;4,4' -dimethoxytrityl chloride with the molar ratio of 1-2 relative to AZO-2 is put in another container, air is removed by pumping, and 1-10 times of volume of dichloromethane is added to obtain a second solution; dropwise adding the second solution into the first solution, and stirring at room temperature in a dark place for reaction overnight; after the reaction is finished, extracting by using water and ethyl acetate, reserving the organic phase, drying, and removing the organic solvent to obtain the AZO-03 product.
- 9. The method for producing a DNA base analog according to claim 4, wherein: introducing a raw material 2-cyanoethyl N, N-diisopropyl phosphoramidite chloride on the basis of an intermediate product AZO-03; taking N, N-diisopropylethylamine as an alkali and a catalyst and dichloromethane as a solvent, and obtaining a final product AZO-04 under the anhydrous and anaerobic reaction conditions.
- 10. The method for producing a DNA base analog according to claim 9, characterized in that: adding AZO-03 into a container, and adding 1-20 times of dichloromethane by volume under the protection of nitrogen; under the condition of ice-water bath, dropwise adding 2-10 times of mol ratio of N, N-diisopropylethylamine and 0.5-2 times of mol ratio of 2-cyanoethyl N, N-diisopropylphosphoramidite, and reacting for 2-4 h in ice bath to obtain AZO-4.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810968214.6A CN109336921B (en) | 2018-08-23 | 2018-08-23 | DNA base analogue, application and synthetic method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810968214.6A CN109336921B (en) | 2018-08-23 | 2018-08-23 | DNA base analogue, application and synthetic method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109336921A CN109336921A (en) | 2019-02-15 |
| CN109336921B true CN109336921B (en) | 2020-06-05 |
Family
ID=65296426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810968214.6A Active CN109336921B (en) | 2018-08-23 | 2018-08-23 | DNA base analogue, application and synthetic method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109336921B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113248556B (en) * | 2021-05-18 | 2022-07-26 | 武汉科技大学 | Assembly of nucleic acid grafted azobenzene, preparation method and application |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1724343A1 (en) * | 2004-02-27 | 2006-11-22 | Japan Science and Technology Agency | Dna enzyme and method of controlling the activity thereof |
| WO2010147673A2 (en) * | 2009-06-19 | 2010-12-23 | University Of Florida Research Foundation, Inc. | Single-dna molecule nanomotor regulated by photons |
| EP2314713A1 (en) * | 2008-07-01 | 2011-04-27 | National University Corporation Nagoya University | Oligonucleotide probe, and use thereof |
| WO2012029434A1 (en) * | 2010-08-31 | 2012-03-08 | 国立大学法人名古屋大学 | Oligonucleotide and use thereof |
| CN103819501A (en) * | 2014-03-19 | 2014-05-28 | 厦门大学 | Methyl propenyl phosphoramidite monomer and synthetic method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011135824A (en) * | 2009-12-28 | 2011-07-14 | Nagoya Univ | Method of detecting target nucleic acid |
-
2018
- 2018-08-23 CN CN201810968214.6A patent/CN109336921B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1724343A1 (en) * | 2004-02-27 | 2006-11-22 | Japan Science and Technology Agency | Dna enzyme and method of controlling the activity thereof |
| EP2314713A1 (en) * | 2008-07-01 | 2011-04-27 | National University Corporation Nagoya University | Oligonucleotide probe, and use thereof |
| WO2010147673A2 (en) * | 2009-06-19 | 2010-12-23 | University Of Florida Research Foundation, Inc. | Single-dna molecule nanomotor regulated by photons |
| WO2012029434A1 (en) * | 2010-08-31 | 2012-03-08 | 国立大学法人名古屋大学 | Oligonucleotide and use thereof |
| CN103819501A (en) * | 2014-03-19 | 2014-05-28 | 厦门大学 | Methyl propenyl phosphoramidite monomer and synthetic method thereof |
Non-Patent Citations (1)
| Title |
|---|
| Molecular Design for Reversing the Photoswitching Mode of Turning ON and OFF DNA Hybridization;Xingguo Liang et al.;《Chem. Asian J. 》;20081231;第3卷;page:553-560 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109336921A (en) | 2019-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ollevier et al. | Bismuth triflate-catalyzed mild and efficient epoxide opening by aromatic amines under aqueous conditions | |
| CN109336921B (en) | DNA base analogue, application and synthetic method thereof | |
| Takemoto et al. | Stereoselective synthesis of nonracemic 1, 3-amino alcohols from chiral 2-vinylaziridines by InI–Pd (0)-promoted metalation | |
| Hansen et al. | A facile formal synthesis of volicitin | |
| CN114409592B (en) | Chiral pyridoxal catalyst with biaryl structure and side chain at C3 position, and preparation method and application thereof | |
| Beresis et al. | Enantioselective Nitration of Chiral (E)-Crotylsilanes: A Concise Asymmetric Synthesis of (E)-Olefin Dipeptide Isosteres | |
| Li et al. | Synthesis of 1, 1-disubstituted-2, 6-diarylcyclohexane-4-ones catalyzed by KF/basic Al2O3 under ultrasound | |
| CN110642737B (en) | Preparation method of amide-substituted (E, E) -configuration branched conjugated diene derivative | |
| CN108164561B (en) | Chiral menthyl phenyl phosphonamide compound and preparation method thereof | |
| Tanaka et al. | Catalytic dehydrogenative N-((triisopropylsilyl) oxy) carbonyl (Tsoc) protection of amines using iPr 3 SiH and CO 2 | |
| CN102807501A (en) | Non-natural chiral amino acid and biological catalysis desymmetrisation preparation method thereof | |
| CN103232507B (en) | Modified nucleoside monomer and synthetic method thereof and application | |
| CN112047842A (en) | 1, 4-diene compound and preparation method and application thereof | |
| Shibata et al. | Synthesis of nonpolar peptide nucleic acid monomers containing fluoroaromatics | |
| Pandey et al. | Diastereoselective Oxyselenylation of 1, n-Diolefins Utilizing PET Generated [PhSeSePh]+. as an Electrophilic Species: An Efficient and General Strategy for the Synthesis of α, α′-trans-Dialkyl Cyclic Ethers | |
| JP4195384B2 (en) | Method for producing optically active 3,5-dihydroxycarboxylic acid derivative | |
| CN115466238B (en) | Dihydrofuran-2 (3H) -imine bridged ring derivative and synthetic method thereof | |
| CN112538506B (en) | Process method for synthesizing chloramphenicol succinate by enzyme catalysis | |
| CN111825594B (en) | (Z) -beta-trifluoromethyl dehydrotryptophan compound and synthetic method and application thereof | |
| JPH02235850A (en) | Production of hydroxy-n-acyl-alpha-amino acid derivative, oligomer and lactone thereof | |
| Wang et al. | Application of modified amino acid as a chiral building block in asymmetric synthesis | |
| WO2004076391A1 (en) | Process for producing optically active compound | |
| JPH0222254A (en) | 2,3-diaminopropionic acid derivative | |
| Lv et al. | Synthesis of dendritic oligodeoxyribonucleotide analogs with nonionic diisopropylsilyl linkage | |
| CN117843727A (en) | Preparation method, intermediate and application of cyclopeptide toxin alpha-Amanitin and/or amanamide |
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 |