Four new C₂₀-diterpenoid alkaloids fromAconitum rotundifolium

Abstract

Four new C-diterpenoid alkaloids, rotundifosines D-G (1-4), along with eight known ones (5-12) were isolated from the whole plant of Aconitum rotundifolium Kar. & Kir. The structures of the compounds were elucidated on the basis of spectroscopic analyses, including HR-ESI-MS and 1D, 2D NMR. Rotundifosine F (3) is a rare C-diterpenoid alkaloid with quaternary ammonium salt. Alkaloids 1-4, 5, 6, 9, and 12 were evaluated for cytotoxicity against MCF-7, HCT-116 and HepG2 human cancer cell lines.

Classification, Toxicity and Bioactivity of Natural Diterpenoid Alkaloids

“…Propionyloxy in C13 and 2-methyl butyryloxy moieties in C2 and a quaternary N base characterise compounds 131–133 obtained from the lateral roots of A. carmichaelii . Compounds 134–138 lose an oxygen group in C11 and C13 [ 67 , 95 , 96 , 97 , 98 , 99 , 100 ].…”

“…The smallest group in the hetidine classification consists of three compounds ( 139–141 in Figure 16 ) [ 99 , 101 , 102 ]. It is distinguished by the presence of the N=CH group, an endocyclic double bond, and a hydroxyl at C5 in all hetidine-DAs [ 97 , 98 , 99 , 101 ]. Rotundifosine F (structure 139 in Figure 16 ) exhibits a cardicine chloride in C17, whereas the DA 140 shows the hordenine group in the same position, and DA 141 brings a (2-methoxyethyl)-benzene ethanol moiety [ 99 ].…”

“…Most vakognavine DAs ( 142–147 in Figure 17 ) come from Aconitum and Delphinium . Structurally, they have a rare double bond between C16 and C17, an aldehyde group in C19, and a characteristic N–Me group [ 56 , 93 , 99 , 103 , 104 , 105 ].…”

“…Few atisine and hetidine-type alkaloids contain N,O- mixed acetal/ketal units [ 77 , 78 , 99 , 101 ].…”

Chemistry and biological activities of hetisine-type diterpenoid alkaloids

“…Seven natural hetisine-type DAs (16,42,43,84,(87)(88), and 150), along with three hydrolysis products, 13-oxocardiopetamine (42a), 13-acetyl-15-oxo-cardiopetamine (42b), 15b-hydroxy-hetisinone (42c), were screened for their insect antifeedant activity against the Colorado potato beetle (CPB, Leptinotarsa decemlineata) and Spodoptera littoralis, as well as their toxicity to insect-derived Sf9 cells (derived from Spodoptera frugiperda pupal ovarian tissue) and mammalian Chinese hamster ovary (CHO) cells (Table 3). 100,101 Among the tested compounds, cardiodine (87), with an EC 50 value of 2.2 mg cm À2 , was found to be the most active CPB antifeedant, followed by glandulosine (84), with an EC 50 value of 4.0 mg cm À2 , which implied that acetylation at both C-3 and C-11 might enhance their CPB antifeedant effects. Hetisinone (16) and cardiopetamine (42) also showed certain activity against L. decemlineata, with EC 50 values of 13.1 and 22.5 mg cm À2 , respectively.…”