Structure, property, biogenesis, and activity of diterpenoid alkaloids containing a sulfonic acid group from Aconitum carmichaelii

Abstract

Three new C20-diterpenoid alkaloids with a sulfonic acid unit, named aconicarmisulfonines B and C (1 and 2) and chuanfusulfonine A (3), respectively, were isolated from the Aconitum carmichaelii lateral roots (“fu zi” in Chinese). Structures of 1–3 were determined by spectroscopic data analysis. Intriguing chemical properties and reactions were observed for the C20-diterpenoid alkaloids: (a) specific selective nucleophilic addition of the carbonyl (C-12) in 1 with CD3OD; (b) interconversion between 1 and 2 in D2O; (c) stereo- and/or regioselective deuterations of H-11α in 1–3 and both H-11α and H-11β in aconicarmisulfonine A (4); (d) TMSP-2,2,3,3-d4 promoted cleavage of the C-12−C-13 bond of 4 in D2O; (e) dehydrogenation of 4 in pyridine-d5, and (f) Na2SO3-assisted dehydrogenation and N-deethylation of songorine (5, a putative precursor of 1–4). Biogenetically, 1 and 2 are correlated with 4, for which the same novel carbon skeleton is proposed to be derived from semipinacol rearrangements via migrations of C-13−C-16 and C-15−C-16 bonds of the napelline-type skeleton, respectively. Meanwhile, 3 is a highly possible precursor or a concurrent product in the biosynthetic pathways of 1, 2, and 4. In the acetic acid-induced mice writhing assay, at 1.0 mg/kg (i.p.), compounds 1, 2, 5, 5a, and 5b exhibited analgesic effects against mice writhing.

Keywords

• Ranunculaceae
• Aconitum carmichaelii
• Sulfonated C20-diterpenoid alkaloid
• Aconicarmisulfonines
• Chuanfusulfonine A
• Analgesic effect