Chiral synthesis method for (-)-galantamin hydrobromide

Abstract

Ethamine compound is obtained by condensing starting materials of 6-bromoisovanillin and tyramine under catalysis of NaBH4 in carbinol. In formylation of ethamine compound, aminic acid and formaldehyde of same amount are used to produce formyl compound, with temperature between 90 DEG C. and 110 DEG C., 8h. Racemic bromonarwedine is obtain by oxidation and cyclization of the formyl compound. Racemic narwedine is obtained by reduction reaction under catalysis of NaCO2H, PPh3, Pd(OAc)2. Racemic narwedine is transformed into (-)-narwedine by a process of crystal inoculation. (-)-narwedine is reduced into unsaturated ketone by (-)-N-methyl ephedrine as chiral reagent, whereby optically active alcohol is obtained, and (-)-galanthamine is also obtained.

Description

technical field

[0001] The invention belongs to the technical field of medicinal chemistry, in particular to a novel method for chiral synthesis of (-)-galanthamine hydrobromide. Background technique

[0002] Galanthamine is a left-handed chiral compound extracted from Lycoris squamigera Maxim and Lycoris aurea Herb or the same plants of the Amaryllidaceae family. It is a highly selective Sexual cholinesterase inhibitor, well tolerated, no hepatotoxicity. Clinically, it was originally used for the sequelae of polio and myasthenia gravis, and now it is used for the treatment of Alzheimer's disease, and it can also improve the memory impairment caused by dementia patients and brain organic diseases. Clinically used (-)-galantamine is usually prepared as hydrobromide.

[0003]

[0004] Alzheimer's disease is a progressive neurodegenerative disorder in the elderly, and its clinical manifestations are mainly memory loss and cognitive dysfunction. Alzheimer's disease is the ...

Images