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

Three new C-20-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 C-20-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-11 alpha in 1-3 and both H-11 alpha and H-11 beta in aconicarmisulfonine A (4); (d) TMSP-2,2,3,3-d(4) promoted cleavage of the C-12-C-13 bond of 4 in D2O; (e) dehydrogenation of 4 in pyridine-d(5), 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. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.