Methods of synthesizing anatabine
Anatabine is obtained by reacting benzophenoneimine with 3-aminomethyl pyridine to form benzylhydrylidene-pyridin-3-yl-methyl-amine. The benzylhydrylidene-pyridin-3-yl-methyl-amine is treated with a non-nucleophilic base and a dielectrophile, such as cis-1,4-dichloro-2-butene, followed by acidification, then basification, to provide anatabine. The resulting anatabine is substantially free from contaminants and displays good stability. In an alternative embodiment, the benzylhydrylidene-pyridin-3-yl-methyl-amine may be used in the synthesis of other alkaloids such as anabasine, nornicotine, N-methylanabasine, and anabaseine.
1. A method of synthesizing anatabine comprising the steps of:
(a) reacting 3-aminomethyl pyridine with benzophenoneimine to obtain a compound of Formula I:
(b) reacting the compound of Formula I with a non-nucleophilic base and a dielectrophile to obtain a compound of Formula II:
wherein X is a halogen,
(c) treating the compound of Formula II with an acid to obtain a compound of Formula III:
wherein X is a halogen; and
(d) treating the compound of Formula III with at least one base to obtain anatabine.
2. The method of claim 1 , further comprising extracting the reaction product obtained in step (d) with methyl tert-butyl ether (MTBE) solvent and removing the solvent by distillation to recover purified anatabine.