CN102690227A - Optical active tetrahydropyridine derivative and preparation method thereof - Google Patents
Optical active tetrahydropyridine derivative and preparation method thereof Download PDFInfo
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- CN102690227A CN102690227A CN2012101788910A CN201210178891A CN102690227A CN 102690227 A CN102690227 A CN 102690227A CN 2012101788910 A CN2012101788910 A CN 2012101788910A CN 201210178891 A CN201210178891 A CN 201210178891A CN 102690227 A CN102690227 A CN 102690227A
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- GMSKMVVIWZTCEN-UKILVPOCSA-N CC(C[C@@H](c(cc1)ccc1Br)N([C@@H]1c(cc2)ccc2Br)c2ccccc2)=C1C(OC)=O Chemical compound CC(C[C@@H](c(cc1)ccc1Br)N([C@@H]1c(cc2)ccc2Br)c2ccccc2)=C1C(OC)=O GMSKMVVIWZTCEN-UKILVPOCSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N O=Cc(cc1)ccc1Br Chemical compound O=Cc(cc1)ccc1Br ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to an optical active tetrahydropyridine derivative and a preparation method thereof. The preparation method includes steps of taking aldehyde, amine and Beta-keto acid ester as raw materials and chiral phosphoric acid as a catalyst to react in an organic solvent for 24-120 hours at a temperature of -50-50 DEG C on the condition of presence of a molecular sieve, and obtaining optical active tetrahydropyridine derivative via purification separation. The method for tetrahydropyridine derivative is mild in reaction conditions, simple in technique and convenient and rapid to operate.Furthermore, the optical active tetrahydropyridine derivative is capable of serving as an intermediate of medicament synthesizing, and has potentially good bioactivity.
Description
Technical field
The present invention relates to a kind of optical activity 5,6-tetrahydropyridine derivative and the method for using the preparation of chiral phosphorus acid catalysis, belong to the synthetic field of nitrogenous heterocyclic chirality.
Background technology
5,6-tetrahydropyridine derivative is a kind of active heterocycle of important biomolecule that has, and can be used as the important intermediate of pharmaceutical prod, also is present in some high-activity natural products, referring to (Curr.Med.Chem.2005,12,551 – 571; Bioorg.Med.Chem.17 (2009) 625 – 633; Bioorg.Med.Chem.2003,11,5229; J.Med.Chem.1988,31,1621; Bioorg.Med.Chem.Lett.2003,13,1359; J.Med.Chem.2005,48,3704; Nat.Prod.Rep.1992,9,491).Particularly document Bioorg.Med.Chem.17 (2009) 625 – 633 have reported that some 5,6-tetrahydropyridine derivatives have superior malaria effect.The report that therefore a lot of catalysis tetrahydrobiopterin synthesis pyridine derivates have been arranged is such as Synthesis 2008,3530 – 3532; Tetrahedron Lett.2010,51,4419 – 4424; Tetrahedron Lett.2007,48,5209 – 5212; ACS Comb.Sci.2011,13,181 – 185; J.Org.Chem.2008,73,8398 – 8402 wait for; But these reports all are about the raceme synthetic, and the example of asymmetric synthesis is not arranged as yet; And the different same structure general formula of optical activity can show very big difference usually on pharmacology, even opposite effect.
Therefore further the preparation method of the high enantioselectivity efficiently of exploitation optical activity 5,6-tetrahydropyridine derivative provides the optical activity 5,6-tetrahydropyridine derivative significant to new medicament screen etc.; Obviously be best approach through the asymmetric method synthesis of optically active of catalysis 5,6-tetrahydropyridine derivative.
Summary of the invention
The purpose of this invention is to provide a kind of structure of optical activity 5,6-tetrahydropyridine derivative, and a kind of reaction temperature and, easy and simple to handle, method that chiral phosphorus acid catalysis that enantioselectivity is high prepares the optical activity 5,6-tetrahydropyridine derivative are provided.
Optical activity 5,6-tetrahydropyridine derivative of the present invention is characterized in that it is levo form or the dextrorotatory form optically active compound with structural formula (1):
In the formula: R
1Be selected from aryl or substituted aryl, heteroaryl or substituted heteroaryl, styryl or substituted styryl, said substituting group be halogen, nitro,
C1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
2Be selected from C
3～C
8Alkyl, benzyl, aryl or substituted aryl, heteroaryl or substituted heteroaryl, said substituting group is halogen, nitro, C
1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
3Be selected from C
1～C
4Alkyl, benzyl, allyl group; R
4Be selected from H, C
1～C
4Alkyl, benzyl.
The preparation method of optical activity 5,6-tetrahydropyridine derivative of the present invention; It is characterized in that with aldehyde, amine and beta-ketoester be raw material, in the presence of molecular sieve, is catalyzer with chirality phosphoric acid; In organic solvent; In-50～50 ℃ of reactions 24～120 hours, purified separation obtained the optical activity 5,6-tetrahydropyridine derivative, and the mol ratio of described aldehyde, amine and beta-ketoester is 2: 2: 1; The mol ratio of described chiral phosphorus acid catalyst and beta-ketoester is 1～20: 100; The mass ratio of described molecular sieve and beta-ketoester is 1～20: 1; Reaction formula is:
In the formula: R
1Be selected from aryl or substituted aryl, heteroaryl or substituted aryl, styryl or substituted styryl, said substituting group is halogen, nitro, C
1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
2Be selected from C
3～C
8Alkyl, benzyl, aryl or substituted aryl, heteroaryl or substituted heteroaryl, said substituting group is halogen, nitro, C
1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
3Be selected from C
1～C
4Alkyl, benzyl, allyl group; R
4Be selected from H, C
1～C
4Alkyl, benzyl.
Among the present invention, described chiral phosphorus acid catalyst can be chiral spiro phosphoric acid or chiral binaphthyl phosphoric acid; Described chiral spiro phosphoric acid catalyst is for having the levo form or the dextrorotatory form optically active compound of structural formula (2), and described chiral binaphthyl phosphoric acid catalyst is for having the levo form or the dextrorotatory form optically active compound of structural formula (3);
In the formula: R is selected from halogen, C
1～C
4Alkyl, aryl or substituted aryl, the substituting group on the said substituted aryl is halogen, C
1~ C
4Alkyl, C
1~ C
4-oxyl, C
1~ C
4Perfluoroalkyl or nitro, the substituting group number on the said substituted aryl can be that 1～5 and substituting group can be identical or different.
Among the present invention, described organic solvent can be ethylene dichloride, benzene, toluene or YLENE.
The present invention adopts the method for chirality phosphoric acid asymmetry catalysis aldehyde, amine and keto ester prepared in reaction optical activity 5,6-tetrahydropyridine derivative, compares with existing compound method, has the following advantages:
1) easy and simple to handle;
2) reaction highly versatile;
3) enantioselectivity is high, can further improve the ee value through Virahol or acetonitrile recrystallization, up to 99%ee.
The practical implementation method
Following examples will help to understand the present invention, but be not limited to content of the present invention:
Embodiment 1
Under nitrogen protection; 0.2 mmole aniline, 150 milligrams of
molecular sieves, 0.01 mmole (S)-O; O '-{ 7,7 '-[6,6 '-two-(3; 5-two (trifluoromethyl) phenyl)-1; The two dihydro indenes of 1 '-spiral shell] } ((S)-1a) is blended in 5 milliliters of toluene solvants with 0.1 mmole methyl acetoacetate phosphoric acid catalyst, is cooled to add 0.2 mmole paranitrobenzaldehyde after-30 ° of C, finishes reaction after 72 hours-30 ° of C reactions and carries out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2a through the silica-gel powder column chromatography, productive rate 75%.The dr value of product is 11: 1, and it is 99%ee that dominant isomer optical purity is measured with HPLC.[Daicel?ChiralpakOD-H,n-hexane/i-propanol=85/15,0.8mL/min,λ=254nm,t(major)=21.99min,t(minor)=29.64min].
1H?NMR(400MHz,CDCl
3)δ2.85(2H,d,J=4.0Hz),3.96(3H,s),5.24-5.26(1H,m),6.37-6.44(4H,m),6.46(1H,s),6.68(1H,t,J=7.2Hz),7.07(1H,d,J=7.2Hz),7.09(1H,d,J=7.2Hz),7.14-7.17(3H,m),7.28(2H,d,J=8.8Hz),7.48(2H,d,J=8.4Hz),8.11(2H,d,J=8.8Hz),8.13(2H,d,J=8.8Hz),10.28(1H,brs)ppm.
Reaction formula is:
Embodiment 2
Under nitrogen protection; Be blended in 0.01 mmole (R)-dinaphthalene phosphoric acid catalyst (1b), 0.2 mmole aniline, 110 milligrams of
molecular sieves and 0.1 mmole methyl acetoacetate in 3 milliliters of toluene solvants; Be cooled to add 0.2 mmole paranitrobenzaldehyde after-30 ° of C; Finish reaction after 72 hours-30 ° of C reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2a through the silica-gel powder column chromatography, productive rate 56%.The dr value of product is 4:1, and it is 89%ee that dominant isomer optical purity is measured with HPLC.
Reaction formula is:
Embodiment 3
Under nitrogen protection; Be blended in 0.1 mmole (S)-volution phosphoric acid catalyst (1a), 2 mmole aniline, 1000 milligrams of
molecular sieves and 1 mmole methyl acetoacetate in 10 milliliters of ethylene dichloride solvents; Add 2 mmole paranitrobenzaldehydes; Finish reaction after 24 hours at room temperature reaction and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2a through the silica-gel powder column chromatography, productive rate 79%.The dr value of product is 5: 1, and it is 73%ee that dominant isomer optical purity is measured with HPLC.
Embodiment 4
Under nitrogen protection; Be blended in 0.1 mmole (R)-volution phosphoric acid catalyst (1c), 2 mmole aniline, 1000 milligrams of
molecular sieves and 1 mmole methyl acetoacetate in 10 milliliters of toluene solvants; Add 2 mmole paranitrobenzaldehydes; Finish reaction after 24 hours in 50 degree reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2a through the silica-gel powder column chromatography, productive rate 65%.The dr value of product is 10: 1, and it is 20%ee that dominant isomer optical purity is measured with HPLC.Reaction formula:
Embodiment 5
Under nitrogen protection; Be blended in 0.015 mmole volution phosphoric acid catalyst (1a), 0.2 mmole aniline, 110 milligrams of
molecular sieves and 0.1 mmole methyl aceto acetate in 5 milliliters of toluene solvants; Be cooled to add 0.2 mmole paranitrobenzaldehyde after-30 ° of C; Finish reaction after 72 hours-30 ° of C reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2b through the silica-gel powder column chromatography, productive rate 69%.The dr value of product is greater than 20: 1, and it is 95%ee that dominant isomer optical purity is measured with HPLC.[Daicel?Chiralpak?OD-H,n-hexane/i-propanol=85/15,0.8mL/min,λ=254nm,t(major)=20.3min,t(minor)=30.7min].
1H?NMR(400MHz,CDCl
3)δ1.23(t,J=7.5Hz,3H),2.46(dd,J=15.5,3.0Hz,1H),2.81(dd,J=15.5,3.0Hz,1H),4.11-4.19(m,1H),4.23-4.29(m,1H),4.66(J=12.0,3.0Hz,1H),6.02(s,1H),6.76(d,J=8.5Hz,2H),6.84(t,J=8.5Hz,1H),7.01(d,J=8.0Hz,2H),7.15(d,J=7.5Hz,2H),7.19(t,J=7.5Hz,1H),7.33(t,J=8.0Hz,2H),7.45(d,J=8.5Hz,2H),7.74(t,J=8.5Hz,2H),8.08(d,J=8.5Hz,2H),8.26(d,J=8.5Hz,2H),10.75(br?s,1H)ppm.
Reaction formula is:
Embodiment 6
Under nitrogen protection; Be blended in 0.01 mmole volution phosphoric acid catalyst (1a), 0.2 mmole aniline, 100 milligrams of
molecular sieves and 0.1 mmole ISOPROPYL ACETOACETATE in 5 milliliters of toluene solvants; Be cooled to add 0.2 mmole paranitrobenzaldehyde after-30 ° of C; Finish reaction after 72 hours-30 ° of C reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2c through the silica-gel powder column chromatography, productive rate 54%.The dr value of product is greater than 20:1, and it is 96%ee that dominant isomer optical purity is measured with HPLC, and this product can further improve the ee value with the Virahol recrystallization, reaches 99%ee.[DaicelChiralpak?OD-H,n-hexane/i-propanol=85/15,0.8mL/min,λ=254nm,t(major)=14.1min,t(minor)=20.6min].
Embodiment 7
Under nitrogen protection; Be blended in 0.01 mmole volution phosphoric acid catalyst (1a), 0.2 mmole aniline, 100 milligrams of
molecular sieves and 0.1 mmole methyl acetoacetate in 3 milliliters of toluene solvants; Be cooled to add 0.2 mmole phenyl aldehyde after-15 ° of C; Finish reaction after 100 hours-15 ° of C reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2d through the silica-gel powder column chromatography, productive rate 53%.The dr value of product is greater than 20:1, and it is 88%ee that dominant isomer optical purity is measured with HPLC.[Daicel?Chiralpak?AD-H,n-hexane/i-propanol=85/15,0.8mL/min,λ=254nm,t(major)=6.6min,t(minor)=10min].
1H?NMR(400MHz,CDCl
3)δ2.78-2.74(d,J=15.2Hz,1H),2.89-2.86(dd,J=15.2,5.6Hz,1H),3.93(s,3H),5.12(s,1H),6.28-6.29(d,J=7.6Hz,2H),6.45(s,1H),6.53-6.52(d,J=8.4Hz,2H),6.61-6.58(t,J=7.2Hz,1H),7.33-7.10(m,15H),10.33(br?s,1H,NH)ppm；HRMS(ESI):MH
+:461.2255。
Embodiment 8
Under nitrogen protection; Be blended in 0.01 mmole volution phosphoric acid catalyst (1d), 0.2 mmole aniline, 100 milligrams of
molecular sieves and 0.1 mmole methyl acetoacetate in 3 milliliters of toluene solvants; Add 0.2 mmole phenyl aldehyde; Finish reaction after 72 hours at room temperature reaction and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2d through the silica-gel powder column chromatography, productive rate 87%.The dr value of product is greater than 20:1, and it is 69%ee that dominant isomer optical purity is measured with HPLC.
Embodiment 9
Under nitrogen protection; 0.02 mmole (S)-O; O '-{ 7,7 '-[6,6 '-two-(3; 5-two (trifluoromethyl) phenyl)-1; The two dihydro indenes of 1 '-spiral shell] } phosphoric acid catalyst (1a), 0.2 mmole aniline, 100 milligrams of
molecular sieves and 0.1 mmole methyl acetoacetate be blended in 5 milliliters of toluene solvants, is cooled to add 0.2 mmole m-nitrobenzaldehyde after-30 ° of C, and finish reaction after 120 hours-30 ° of C reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2e through the silica-gel powder column chromatography, productive rate 55%.The dr value of product is 5:1, and it is 96%ee that dominant isomer optical purity is measured with HPLC, and this product can further improve the ee value with the Virahol recrystallization, reaches 99%ee.[Daicel?Chiralpak?AD-H,n-hexane/i-propanol=80/20,1.0mL/min,λ=254nm,t(major)=9.1min,t(minor)=32.9min].
1H?NMR(400MHz,CDCl
3)δ2.90(d,J=3.7Hz,2H,H-5),4.03(s,3H,OCH
3),5.35(br?s,1H,H-6),6.40–6.50(m,5H,ArH,and?H-2),6.71(t,J=7.3Hz,1H,ArH),7.09–7.15(m,5H,ArH),7.44–7.52(m,3H,ArH),7.69(d,J=7.6Hz,1H,ArH),7.95(s,1H,ArH),8.10(m,2H,ArH),8.22(s,1H,ArH),10.35(br?s,1H,NH)ppm.
Reaction formula is:
Embodiment 10
Under nitrogen protection; 0.02 mmole (S)-O; O '-{ 7,7 '-[6,6 '-two-(3; 5-two (trifluoromethyl) phenyl)-1; The two dihydro indenes of 1 '-spiral shell] } phosphoric acid catalyst (1a), 0.2 mmole aniline, 100 milligrams of
molecular sieves and 0.1 mmole methyl acetoacetate be blended in 5 milliliters of toluene solvants, is cooled to add 0.2 mmole p-bromobenzaldehyde after-30 ° of C, and finish reaction after 96 hours-30 ° of C reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2f through the silica-gel powder column chromatography, productive rate 50%.The dr value of product is 5.5:1, and it is 88%ee that dominant isomer optical purity is measured with HPLC, and this product can further improve the ee value with the Virahol recrystallization, reaches 99%ee.[Daicel?Chiralpak?AD-H,n-hexane/i-propanol=80/20,1.0mL/min,λ=254nm,t(major)=9.1min,t(minor)=32.9min].
1H?NMR(400MHz,CDCl
3)δ2.75(dd,J=15.0and?2.3Hz,1H,H-5a),2.86(dd,J=15.0and?5.3Hz,1H,H-5b),3.95(s,3H,OMe),5.08(br?s,1H,H-6),6.38-6.70(m,5H,4ArH,and?H-2),6.76–6.87(m,1H,ArH),7.01–7.55(m,9H,ArH),7.69–7.73(d,J=7.0Hz,4H,ArH),10.35(br?s,1H,NH)ppm.
Reaction formula is:
Embodiment 11
Under nitrogen protection; 0.01 mmole (R)-O; O '-{ 7,7 '-[6,6 '-two-(3; 5-two (trifluoromethyl) phenyl)-1; The two dihydro indenes of 1 '-spiral shell] } ((R)-1a), 0.2 mmole aniline, 100 milligrams of
molecular sieves and 0.1 mmole methyl acetoacetate are blended in 5 milliliters of toluene solvants phosphoric acid catalyst, are cooled to add 0.2 mmole paranitrobenzaldehyde after-30 ° of C, finish reaction after 72 hours-30 ° of C reactions and carry out aftertreatment; Obtain 5,6-tetrahydropyridine derivative 2a-1 through the silica-gel powder column chromatography, productive rate 70%.The dr value of product is 10: 1, and it is 98%ee that dominant isomer optical purity is measured with HPLC.[Daicel?Chiralpak?OD-H,n-hexane/i-propanol=85/15,0.8mL/min,λ=254nm,t(minor)=21.99min,t(major)=29.64min].
Claims (4)
1. optical activity 5,6-tetrahydropyridine derivative is characterized in that it is levo form or the dextrorotatory form optically active compound with structural formula (1):
In the formula: R
1Be selected from aryl or substituted aryl, heteroaryl or substituted heteroaryl, styryl or substituted styryl, said substituting group is halogen, nitro, C
1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
2Be selected from C
3～C
8Alkyl, benzyl, aryl or substituted aryl, heteroaryl or substituted heteroaryl, said substituting group is halogen, nitro, C
1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
3Be selected from C
1～C
4Alkyl, benzyl, allyl group; R
4Be selected from H, C
1～C
4Alkyl, benzyl.
2. the preparation method of the described optical activity 5,6-tetrahydropyridine derivative of claim 1; It is characterized in that with aldehyde, amine and beta-ketoester be raw material, in the presence of molecular sieve, is catalyzer with chirality phosphoric acid; In organic solvent; In-50～50 ℃ of reactions 24～120 hours, purified separation obtained the optical activity 5,6-tetrahydropyridine derivative, and the mol ratio of described aldehyde, amine and beta-ketoester is 2: 2: 1; The mol ratio of described chiral phosphorus acid catalyst and beta-ketoester is 1～20: 100; The mass ratio of described molecular sieve and beta-ketoester is 1～20: 1; Reaction formula is:
In the formula: R
1Be selected from aryl or substituted aryl, heteroaryl or substituted heteroaryl, styryl or substituted styryl, said substituting group is halogen, nitro, C
1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
2Be selected from C
3～C
8Alkyl, benzyl, aryl or substituted aryl, heteroaryl or substituted heteroaryl, said substituting group is halogen, nitro, C
1～C
4Alkyl or C
1～C
4-oxyl in 1～3; R
3Be selected from C
1～C
4Alkyl, benzyl, allyl group; R
4Be selected from H, C
1～C
4Alkyl, benzyl.
3. the preparation method of optical activity 5,6-tetrahydropyridine derivative according to claim 2 is characterized in that described chiral phosphorus acid catalyst is chiral spiro phosphoric acid or chiral binaphthyl phosphoric acid; Above-mentioned chiral spiro phosphoric acid catalyst is for having the levo form or the dextrorotatory form optically active compound of structural formula (2), and above-mentioned chiral binaphthyl phosphoric acid catalyst is for having the levo form or the dextrorotatory form optically active compound of structural formula (3);
In the formula: R is selected from halogen, C
1~ C
4Alkyl, aryl or substituted aryl, the substituting group on the said substituted aryl is halogen, C
1~ C
4Alkyl, C
1~ C
4-oxyl, C
1~ C
4Perfluoroalkyl or nitro, the substituting group number on the said substituted aryl can be that 1～5 and substituting group can be identical or different.
4. the preparation method of optical activity 5,6-tetrahydropyridine derivative according to claim 2 is characterized in that described organic solvent is ethylene dichloride, benzene, toluene or YLENE.
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Cited By (5)
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| CN104031050A (en) * | 2014-05-16 | 2014-09-10 | 浙江大学 | Method for chiral spirocyclic phosphoric acid catalytic synthesis of optically active benzoazepinoindole derivative |
| CN104774173A (en) * | 2015-04-29 | 2015-07-15 | 安徽工业大学 | Method for catalized preparation of tetrahydropyridine derivative through acidic ionic liquid |
| CN105017238A (en) * | 2015-06-25 | 2015-11-04 | 浙江大学 | Method for chiral spirophosphonate catalyzed synthesis of optically active 2H-1,4-benzoxazine-2-one derivative |
| CN111704576A (en) * | 2020-06-17 | 2020-09-25 | 菏泽学院 | Synthesis method and application of axial chiral 9-aryl tetrahydroacridine |
| CN113173925A (en) * | 2021-04-30 | 2021-07-27 | 浙江大学 | Benzoxoepinoindole derivative and preparation method thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104031050A (en) * | 2014-05-16 | 2014-09-10 | 浙江大学 | Method for chiral spirocyclic phosphoric acid catalytic synthesis of optically active benzoazepinoindole derivative |
| CN104774173A (en) * | 2015-04-29 | 2015-07-15 | 安徽工业大学 | Method for catalized preparation of tetrahydropyridine derivative through acidic ionic liquid |
| CN104774173B (en) * | 2015-04-29 | 2017-03-08 | 安徽工业大学 | A kind of method that utilization presence of acidic ionic liquid catalyst prepares 5,6-tetrahydropyridine derivative |
| CN105017238A (en) * | 2015-06-25 | 2015-11-04 | 浙江大学 | Method for chiral spirophosphonate catalyzed synthesis of optically active 2H-1,4-benzoxazine-2-one derivative |
| CN105017238B (en) * | 2015-06-25 | 2017-10-17 | 浙江大学 | A kind of method that chiral spiro-phosphate catalyzes and synthesizes the ketone derivatives of 1,4 benzoxazines of optical activity 2H 2 |
| CN111704576A (en) * | 2020-06-17 | 2020-09-25 | 菏泽学院 | Synthesis method and application of axial chiral 9-aryl tetrahydroacridine |
| CN113173925A (en) * | 2021-04-30 | 2021-07-27 | 浙江大学 | Benzoxoepinoindole derivative and preparation method thereof |
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