6159-55-3

Basic information

• Product Name: VASICINE
• Synonyms: 1-b)quinazolin-3-ol,1,2,3,9-tetrahydro-pyrrolo(;vasicin;1,2,3,9-TETRAHYDROPYRROLO[2,1-B]QUINAZOLIN-3-OL;AKOS NCG1-0080;VITAS-BB TBB000541;VASICINE;PEGANINE;C10733
• CAS NO: 6159-55-3
• Molecular Formula: C₁₁H₁₂N₂O
• Molecular Weight: 188.23
• EINECS: 228-180-8
• Product Categories: Miscellaneous Natural Products;Alkaloids
• Mol File: 6159-55-3.mol
• Article Data: 1

Chemical Properties

• Melting Point: 211.5°C
• Boiling Point: 323.23°C (rough estimate)
• Flash Point: 179.9 °C
• Appearance: /
• Density: 1.1124 (rough estimate)
• Vapor Pressure: 2.98E-06mmHg at 25°C
• Refractive Index: 1.5850 (estimate)
• PKA: 13.08±0.20(Predicted)
• CAS DataBase Reference: VASICINE(CAS DataBase Reference)
• NIST Chemistry Reference: VASICINE(6159-55-3)
• EPA Substance Registry System: VASICINE(6159-55-3)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• RIDADR: 1544
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 6159-55-3(Hazardous Substances Data)

Usage

Description

This quinazoline alkaloid was first isolated from the leaves of Adhatoda vasica Nees by Hooper and subsequently discovered in Peganum harmala under the name Peganine. The base is optically inactive although Spath and Kesztler have reported the isolation of the (-)-form from the fresh leaves of A. vasica and Rosenfeld and Kolesnikow have obtained the same form from the flowers and stems of Peganum harmala. The salts are readily obtained crystalline, e.g. the hydrochloride dihydrate, m.p. 208°C (dry); hydriodide dihydrate, m.p. 195°C (dry); picrate, m.p. 199°C (dec.) and the methiodide, m.p. 187°C.With AcOH, the alkaloid gives an anomalous acetyl derivative, m.p. 165°C, subsequently shown to be N-acetylpedadiene. Oxidation with KMn04 gives 4-quinazolone and 4-keto-3 :4-dihydroxyquinazolyl-3-acetic acid, the latter characterized as the methyl ester, m.p. 152°C.The crude drug from A. vasica is used in India as a remedy for asthma while the pure alkaloid acts as a bronchodilator.

References

Hooper., Pharm. J., 18,841 (1888) Sen, Ghose.,J. Ind. Chem. Soc., 1,315 (1924) Ghose., ibid, 4, 1 (1927) Spath, Nakawitz., Ber., 67,45 (1934) Spath, Kuffner., ibid, 67, 1494 (1934) Narang, Ray., Chem. & Ind., 53,698 (1934) Hanford, Liang, Adams., J. Amer. Chem. Soc., 56, 2780 (1934) Ghoseetal., ibid, 57,921,951 (1935) Rosenfeld, Kolesnikov., Ber., 69, 2022 (1936) Pharmacology: Chopra., Ind. Med. Gaz., 60, 354 (1925) Tutaev, Makarova., Trans. Ukraine Inst. Exp. Pharm., 1,32 (1938)

InChI:InChI=1/C11H12N2O/c14-10-5-6-13-7-8-3-1-2-4-9(8)12-11(10)13/h1-4,10,14H,5-7H2/t10-/m0/s1

Synthetic route

vasicine (6159-56-4, 176200-11-6) → (+)-vasicinol (6159-55-3)

Conditions	Yield
With D-tartaric acid

vasicine (6159-56-4, 176200-11-6) → vasicine (18549-38-7) + (+)-vasicinol (6159-55-3)

Conditions	Yield
With 2,2'-iminobis[ethanol] In ethanol Resolution of racemate;

(+)-vasicinol (6159-55-3) → (3S)-1-[(2-aminophenyll)methyl]pyrrolidin-3-ol (1227263-77-5)

Conditions	Yield
With sodium tetrahydroborate In methanol; water for 2h; Solvent;	99%
With sodium tetrahydroborate In methanol; water at 20℃; for 2h;	99%
With sodium tetrahydroborate; water In methanol at 20℃;	90%

(+)-vasicinol (6159-55-3) → (3S)-1,2,3,3a,4,9-hexahydropyrrolo[2,1-b]quinazolin-3-ol

Conditions	Yield
With sodium tetrahydroborate In methanol at 20℃; for 1h; Solvent;	95%

(+)-vasicinol (6159-55-3) → (3S)-1-[(2-aminophenyll)methyl]pyrrolidin-3-ol (1227263-77-5) + (3S)-1,2,3,3a,4,9-hexahydropyrrolo[2,1-b]quinazolin-3-ol

Conditions	Yield
With sodium tetrahydroborate In methanol; water for 2h; Solvent;	A 80% B 10%

(S)-(+)-2-methoxy-2-trifluoromethyl-2-phenylacetyl chloride (39637-99-5, 20445-33-4) + (+)-vasicinol (6159-55-3) → vasicine (R)-α-methoxy-α-(trifluoromethyl)phenylacetic acid ester

(R)-methoxytrifluoromethylphenylacetyl chloride (20445-33-4, 39637-99-5) + (+)-vasicinol (6159-55-3) → vasicine (S)-α-methoxy-α-(trifluoromethyl)phenylacetic acid ester

(+)-vasicinol (6159-55-3) → (R)-N-benzyl-3-hydroxypyrrolidine (101385-90-4, 101930-07-8, 101979-03-7, 775-15-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: water; sodium tetrahydroborate / methanol / 10 h / 20 °C 2.1: hypophosphorous acid; sodium azide; sulfuric acid; acetic acid / water / 39.5 h / 5 °C 2.2: pH 8 3.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 0.33 h / 0 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere 4.1: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate / methanol; water / 2 h 2.1: isopentyl nitrite / N,N-dimethyl-formamide / 0.5 h / 65 °C 3.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran / 0.33 h / 0 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere 4.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran / 2 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate / methanol; water / 2 h 2.1: isopentyl nitrite / N,N-dimethyl-formamide / 0.5 h / 65 °C 3.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran / 0.33 h / 0 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere 4.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran / 2 h / 0 °C View Scheme

(+)-vasicinol (6159-55-3) → (S)-N-benzyl-3-hydroxypyrrolidine (101385-90-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: water; sodium tetrahydroborate / methanol / 10 h / 20 °C 2.1: hypophosphorous acid; sodium azide; sulfuric acid; acetic acid / water / 39.5 h / 5 °C 2.2: pH 8 View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol; water / 2 h 2: isopentyl nitrite / N,N-dimethyl-formamide / 0.5 h / 65 °C View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol; water / 2 h 2: isopentyl nitrite / N,N-dimethyl-formamide / 0.5 h / 65 °C View Scheme

(+)-vasicinol (6159-55-3) → (3R)-1-(phenylmethyl)pyrrolidin-3-ol Acetate (116143-02-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: water; sodium tetrahydroborate / methanol / 10 h / 20 °C 2.1: hypophosphorous acid; sodium azide; sulfuric acid; acetic acid / water / 39.5 h / 5 °C 2.2: pH 8 3.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 0.33 h / 0 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate / methanol; water / 2 h 2.1: isopentyl nitrite / N,N-dimethyl-formamide / 0.5 h / 65 °C 3.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran / 0.33 h / 0 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate / methanol; water / 2 h 2.1: isopentyl nitrite / N,N-dimethyl-formamide / 0.5 h / 65 °C 3.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran / 0.33 h / 0 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere View Scheme

(+)-vasicinol (6159-55-3) → 3-chloro-3-deoxyvasicine

Conditions	Yield
With POCl3#PCl5

(+)-vasicinol (6159-55-3) → deoxypeganine (495-59-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: POCl3#PCl5 2: View Scheme

(+)-vasicinol (6159-55-3) → (S)-3-hydroxy-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (486-64-6)

Conditions	Yield
With dihydrogen peroxide In acetone

(+)-vasicinol (6159-55-3) → 2-[(3-chloropyrrolidin-1-yl)methyl]benzenamine

Conditions	Yield
Multi-step reaction with 2 steps 1: POCl3#PCl5 2: sodium tetrahydroborate / methanol; water / 2 h View Scheme

(+)-vasicinol (6159-55-3) → 2-(pyrrolidin-1-ylmethyl)benzenamine (55727-59-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: POCl3#PCl5 2: 3: sodium tetrahydroborate / methanol; water / 2 h View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions 8.1: copper(II) sulfate; sodium L-ascorbate / water; tert-butyl alcohol / 6 h / 50 - 60 °C View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-(4-phenyl-1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions 8.1: copper(II) sulfate; sodium L-ascorbate / water; tert-butyl alcohol / 6 h / 50 - 60 °C View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-(4-hexyl-1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions 8.1: copper(II) sulfate; sodium L-ascorbate / water; tert-butyl alcohol / 6 h / 50 - 60 °C View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-(4-(4-pentylphenyl)-1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions 8.1: copper(II) sulfate; sodium L-ascorbate / water; tert-butyl alcohol / 6 h / 50 - 60 °C View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-(4-pentyl-1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions 8.1: copper(II) sulfate; sodium L-ascorbate / water; tert-butyl alcohol / 6 h / 50 - 60 °C View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-(4-propyl-1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions 8.1: copper(II) sulfate; sodium L-ascorbate / water; tert-butyl alcohol / 6 h / 50 - 60 °C View Scheme

(+)-vasicinol (6159-55-3) → (S)-1-(2-(pyridin-4-ylamino)benzyl)pyrrolidin-3-ol

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; methanol / water 2: potassium carbonate / toluene / 6 h / Reflux View Scheme

(+)-vasicinol (6159-55-3) → (2-((3-((tert-butyldimethylsilyl)oxy)pyrrolidin-1-yl)methyl)phenyl)pyridin-4-amine

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; methanol / water 2: potassium carbonate / toluene / 6 h / Reflux 3: 1H-imidazole / dichloromethane / 20 h / 20 °C View Scheme

(+)-vasicinol (6159-55-3) → (S)-(3-((tertbutyldimethylsilyl)oxy)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium tetrahydroborate; methanol / water 2: potassium carbonate / toluene / 6 h / Reflux 3: 1H-imidazole / dichloromethane / 20 h / 20 °C 4: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux View Scheme

(+)-vasicinol (6159-55-3) → (S)-(3-hydroxypyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium tetrahydroborate; methanol / water 2: potassium carbonate / toluene / 6 h / Reflux 3: 1H-imidazole / dichloromethane / 20 h / 20 °C 4: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C View Scheme

(+)-vasicinol (6159-55-3) → (S)-tert-butyl(2-(3-hydroxypyrrolidine-1-carbonyl)phenyl)(pyridin-4-yl)carbamate

Conditions	Yield
Multi-step reaction with 6 steps 1: sodium tetrahydroborate; methanol / water 2: potassium carbonate / toluene / 6 h / Reflux 3: 1H-imidazole / dichloromethane / 20 h / 20 °C 4: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6: tetrahydrofuran / 5 h / 25 °C View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-azidopyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions View Scheme

(+)-vasicinol (6159-55-3) → (R)-(3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)pyrrolidin-1-yl)(2-(pyridin-4-ylamino)phenyl)methanone

Conditions

Yield

Multi-step reaction with 8 steps 1.1: sodium tetrahydroborate; methanol / water 2.1: potassium carbonate / toluene / 6 h / Reflux 3.1: 1H-imidazole / dichloromethane / 20 h / 20 °C 4.1: benzyl(triethyl)ammoniumpermanganate / dichloromethane / 4 h / Reflux 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C 6.1: tetrahydrofuran / 5 h / 25 °C 7.1: triethylamine; dmap; p-toluenesulfonyl chloride / dichloromethane / 12.5 h / 0 - 15 °C 7.2: 4 h / 60 °C 7.3: 1 h / Acidic conditions 8.1: copper(II) sulfate; sodium L-ascorbate / water; tert-butyl alcohol / 6 h / 50 - 60 °C View Scheme

(+)-vasicinol (6159-55-3) → (S)-methyl-9-((2-((3-hydroxypyrrolidin-1-yl)methyl)phenyl)-amino)-9-oxononanoate

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol; water / 2 h / 20 °C 2: boric acid / toluene / 3 h / Molecular sieve; Inert atmosphere; Reflux View Scheme

(+)-vasicinol (6159-55-3) → (S)-methyl-5-((2-((3-hydroxypyrrolidin-1-yl)methyl)phenyl)-amino)-5-oxopentanoate

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol; water / 2 h / 20 °C 2: boric acid / toluene / 3 h / Molecular sieve; Inert atmosphere; Reflux View Scheme

(+)-vasicinol (6159-55-3) → (S)-methyl 6-((2-((3-hydroxypyrrolidin-1-yl)methyl)phenyl)-amino)-6-oxohexanoate

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / methanol; water / 2 h / 20 °C 2: boric acid / toluene / 3 h / Molecular sieve; Inert atmosphere; Reflux View Scheme

Upstream product

• 6159-56-4 vasicine 

Downstream Products

• 116183-79-0 (3S)-3-<(4-tolylsulfonyl)oxy>-1-(phenylmethyl)pyrrolidine 
• 114715-39-8 (R)-1-benzyl-3-aminopyrrolidine 
• 116183-80-3 (3R)-3-<(4-tolylsulfonyl)oxy>-1-(phenylmethyl)pyrrolidine 
• 114715-38-7 (3S)-1-benzyl-3-pyrrolidinamine 

Relevant articles and documents

Stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic pharmacodynamics, and toxic properties of vasicine enantiomers in vitro and in vivo

Vasicine (VAS) is a potential natural cholinesterase inhibitor for treatment of Alzheimer's disease. Due to one chiral centre (C-3) presenting in molecule, VAS has two enantiomers, d-vasicine (d-VAS) and l-vasicine (l-VAS). The study was undertaken to investigate the stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic effect and acute toxicity of VAS enantiomers. In results, the glucuronidation metabolic rate of l-VAS was faster than d-VAS in human liver microsomes and isoenzymes tests, and it was proved that the UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B15 were the major metabolic enzymes for glucuronidation of l-VAS, while only UGT1A9 for d-VAS, which take responsibility of the significantly less metabolic affinity of d-VAS than l-VAS in HLM and rhUGT1A9. The plasma exposure of d-VAS in rats was 1.3-fold and 1.6-fold higher than that of l-VAS after intravenous and oral administration of d-VAS and l-VAS, respectively. And the plasma exposure of the major glucuronidation metabolite d-VASG was one of tenth of l-VASG or more less, no matter by intravenous or oral administration. Both d-VAS and l-VAS were exhibited promising acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, and the BChE inhibitory activity of d-VAS with IC50 of 0.03 ± 0.001 μM was significantly stronger than that of l-VAS with IC50 of 0.98 ± 0.19 μM. The molecular docking results indicated that d-VAS and l-VAS could bind to the catalytic active site (CAS position) either of human AChE and BChE, and the BChE combing ability of d-VAS (the score of GBI/WAS dG ?7.398) was stronger than that of l-VAS (the score of GBI/WAS dG ?7.135). Both d-VAS and l-VAS could improving the learning and memory on scopolamine-induced memory deficits in mice. The content of acetylcholine (ACh) after oral administration d-VAS increased more than that of l-VAS in mice cortex, through inhibiting cholinesterase (ChE) and increasing choline acetyltransferase (ChAT). In addition, the LD50 value of d-VAS (282.51 mg·kg?1) was slight lower than l-VAS (319.75 mg·kg?1). These results indicated that VAS enantiomers displayed significantly stereoselective metabolic, pharmacokinetics, anti-amnesic effect and toxic properties in vitro and in vivo. The d-VAS might be the dominant configuration for treating Alzheimer's disease.