Pyrolappaconitine, one new alkaloid isolated from sand-fried Aconitum sinomontanum Nakai with less toxicity and analgesic activity.

Aconitum sinomontanum Nakai is a traditional Chinese medicinal herb whose alkaloids serve as both its analgesic constituents and toxic components. Although sand-frying can reduce the toxicity of alkaloids, the chemical constituents of sand-fried A. sinomontanum have not been investigated. To address the issue, a phytochemical investigation was conducted on the sand-fried product of A. sinomontanum. One new compound (1) and ten known compounds (2-11) were isolated from the processed product using chromatographic separation techniques. The absolute configuration was further determined by single-crystal X-ray diffraction analysis for compound 1. Among the known isolates, compounds 2 and 10 were obtained from the processed product of A. sinomontanum for the first time, and the NMR data of compound 2 were fully reported. Based on structural similarities and literature precedents, reasonable hypotheses for the transformation pathways of the major alkaloids during sand-frying were proposed. The acute toxicity assay exhibited LD50 values of 239.9 mg/kg, 152.8 mg/kg, 8.1 mg/kg, 13.5 mg/kg, and 24.2 mg/kg for compounds 1, 3, 5, 6, and 8, respectively. Furthermore, pyrolappaconitine (1) demonstrated peripheral analgesic activity, with an ED50 value of 16.1 mg/kg.