Lycaconitine Revisited:  Partial Synthesis and Neuronal Nicotinic Acetylcholine Receptor Affinities

Abstract

The norditerpenoid alkaloid lycaconitine (2) was synthesized from lycoctonine (3) and its affinity determined for two neuronal nicotinic acetylcholine receptor subtypes. The structure of 2 was confirmed by a combination of spectroscopic methods.

New diterpenoid alkaloids fromAconitum heterophyllum Wall: Selective butyrylcholinestrase inhibitors

“…The Thus on the basis of above spectral data, the structure of compound 1 was deduced as heterophyllinine-A. Heterophyllinine-B (2), was obtained as a white amorphous powder, and was assigned the molecular formula C 24 H 35 NO 4 , on the basis of EI-MS (M þ m/z ¼ 401), and NMR spectral data. The 1 H-and 13 C-NMR spectra of heterophyllinine-B (2) exhibited a close resemblance to that of the known compound isoatisine [20,21] Thus on the basis of above spectral data, the structure of compound 2 was deduced as heterophyllinine-B.…”

“…Some aconitine and mesaconitine derivatives possess potent analgesic and anti-inflammatory activities [3]. The methyllycaconitine and lycaconitine exhibited neuronal nicotinic acetylcholine receptor affinity [4]. Lycaconitine, obtained from several Aconitum species, was found to be effective against multi-drug resistant cancers.…”

Nicotinic Agonists, Antagonists, and Modulators From Natural Sources

“…No radioactive agonist for α 7 receptors is available. The structurally related alkaloids elatine and nudicauline, both of which contain the methyl succinimidobenzoate moiety of methyllaconitine, had as great an affinity for α 7 receptors as methyllyaconitine (Hardick et al, 1996), while lycaconitine, which lacks only the methyl of the succimidobenzoate moiety had a 20-fold lower affinity (Jacyno et al, 1996). Simpler analogs of methyllycaconitine have been synthesized, but they had lost activity at α 7 receptors, being converted to noncompetitive blockers of α 3 β 4 receptors (Bryant et al, 2002;Ismail and Bergmeier, 2002).…”

A Review of Advances in the Synthesis of Analogues of the Delphinium ­Alkaloid Methyllycaconitine

“…Jacyno et al 31 reported a synthesis of lycaconitine (9) from lycoctonine (5) using only a single step to incorporate the succinimido anthranilate, in contrast to the twostep procedure utilised by Blagborough and co-workers. Anthranilic acid (14) and succinic anhydride were condensed in hot chloroform to afford the ring-opened amidodiacid 15a (Scheme 2), which was then cyclised with triethylamine in toluene to form the imide 15b.…”