Selective N-demethylation of galanthamine to norgalanthamine via a non classical Polonovski reaction

Mary, Aude; Renko, Dolor; Guillou, Catherine; Thal, C.

doi:10.1016/s0040-4039(97)01097-6

Cited by 41 publications

(24 citation statements)

References 9 publications

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“…The galantamine was demethylated following a known procedure . The reaction of norgalantamine with the initially prepared bromides 6 – 10 in dry acetonitrile, and potassium carbonate as a base led to the set of target compounds 1 – 5 (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Docking-based Design of Galantamine Derivatives with Dual-site Binding to Acetylcholinesterase

et al. 2016

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The enzyme acetylcholinesterase is a key target in the treatment of Alzheimer's disease because of its ability to hydrolyze acetylcholine via the catalytic binding site and to accelerate the aggregation of amyloid-β peptide via the peripheral anionic site (PAS). Using docking-based predictions, in the present study we design 20 novel galantamine derivatives with alkylamide spacers of different length ending with aromatic fragments. The galantamine moiety blocks the catalytic site, while the terminal aromatic fragments bind in PAS. The best predicted compounds are synthesized and tested for acetylcholinesterase inhibitory activity. The experimental results confirm the predictions and show that the heptylamide spacer is of optimal length to bridge the galantamine moiety bound in the catalytic site and the aromatic fragments interacting with PAS. Among the tested terminal aromatic fragments, the phenethyl substituent is the most suitable for binding in PAS.

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Section: Resultsmentioning

confidence: 99%

Docking-based Design of Galantamine Derivatives with Dual-site Binding to Acetylcholinesterase

et al. 2016

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“…59 Alkylation of norgalantamine 2 with the indole-based bromides 3a-d was realized via nucleophilic substitutions. 57 Thus, heating of 2 with bromides 3a-d in acetonitrile in the presence of K 2 CO 3 as a base for 24 h afforded the targeted compounds 1a-d in good yields and excellent purity after flash column chromatography (Scheme 2).…”

Section: Synthesis Of the Best Predicted Galantamine Derivativesmentioning

confidence: 99%

Galantamine derivatives with indole moiety: Docking, design, synthesis and acetylcholinesterase inhibitory activity

Atanasova

Stavrakov

Philipova

et al. 2015

Bioorganic & Medicinal Chemistry

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“…The N ‐demethylation of the galanthamine‐ N ‐oxide is sensitive to the competition from the benzyl effect [34]. However, the N ‐demethylation has been obtained with a yield of 76% by stirring at 10°C the N ‐oxide in methanol containing iron(II) sulfate.…”

Section: Resultsmentioning

confidence: 99%

A convenient racemic synthesis of two isomeric tetrahydropyridyl alkaloids: Isoanatabine and anatabine

Rouchaud

Kem

2010

Journal of Heterocyclic Chem

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Anatabine is a major alkaloid in Nicotiana tabacum and its isomer, isoanatabine, was recently found in a marine worm. Reduction of 1-methylpyridinium iodide with sodium borohydride gave 1-methyl-3-piperideine, which was transformed with hydrogen peroxide into the N-oxide. Reaction of the N-oxide successively with trifluoroacetic anhydride and potassium cyanide gave 2-cyano-1-methyl-3-piperideine. Its reaction with 3-pyridylmagnesium chloride gave (6)-N-methyl-isoanatabine. This was transformed with m-chloroperbenzoic acid into the N-oxide which was N-demethylated with iron(II) sulfate, giving (6)-isoanatabine. The successive applications of literature procedures for the N-demethylation by decomposition of N-oxide contributed to the knowledge of the mechanism of this oxidative rearrangement. On the other hand, the reduction of 1-methylpyridinium iodide with sodium borohydride and with potassium cyanide present since the start of the reaction in a two layer ether-water system, gave 2-cyano-1-methyl-4-piperideine. This was transformed into (6)-anatabine by the same sequence of reactions used for the synthesis of (6)-isoanatabine.

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Selective N-demethylation of galanthamine to norgalanthamine via a non classical Polonovski reaction

Cited by 41 publications

References 9 publications

Docking-based Design of Galantamine Derivatives with Dual-site Binding to Acetylcholinesterase

Docking-based Design of Galantamine Derivatives with Dual-site Binding to Acetylcholinesterase

Galantamine derivatives with indole moiety: Docking, design, synthesis and acetylcholinesterase inhibitory activity

A convenient racemic synthesis of two isomeric tetrahydropyridyl alkaloids: Isoanatabine and anatabine

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