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

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.