Studies On Alkaloids From Aconitum Carmichaelii Debeaux

Aconitum family has a long medicinal history as an important medicinal plant in China,and many medicinal herbal books have related records.Aconitum carmichaelii Debeaux is mainly distributed in Sichuan,Yunnan and Shaanxi Provinces in China.Its parent and lateral roots are known as'Chuanwu''and'Fuzi'',which are essential herbal medicines for the treatment of neuralgia,rheumatalgia,and cardianeuria in Chinese medicine.Modern pharmacological studies have shown that diterpenoid alkaloids account for the major effects,such as anti-inflammatory,analgesic,cardioactive and anti-cancer activities.To discover the new and potentially bioactive diterpenoid alkaloids,and further facilitate the development and application of A.carmichaelii,investigation on the alkaloid composition of this plant has been carried out.In this paper,solvent extraction,acid extraction and alkali precipitation,and extraction methods were used to gain the crude alkaloid,which was then purified by various column chromatography,including silica gel,reverse phase silica gel and alkaline Al₂O₃,to obtain28 compounds.Their structures were confirmed by extensive spectroscopic methods,including HRESI-MS,IR,and NMR.Carmichasines A-D were determined as four new compounds,in which carmichasine A was the first natural C₁₉-diterpenoid alkaloid possessing a cyano group?-C?N?.In addition,twenty-four known compounds were identified as two C₁₉-diterpenoid alkaloid with the cleavage of C?8?-C?15?bond:nagarines A and B,three napelline-type C₂₀-diterpenoid alkaloids:songorine,songoramine and15-acetylsongoramine,and nineteen aconitine-type C₁₉-diterpenoid alkaloids:talatisamine,chasmanine,14-acetyltalatisamine,3-deoxyhokbusine A,14-benzoylaconine,hypaconitine,mesaconitine,aconitine,beiwutine,sachaconitine,karacoline,14-benzoylchasmanine,6-epiforsticine,15-?-hydroxyneoline,pengshenine A,8-OEt-14-benzoylmesaconine,neoline,6-epichasmanine and subcusine.Furthermore,nagarines A and B were found for the second time in nature after being isolated from Aconitum nagarum as new skeleton.This finding further confirmed the existence of this type of skeleton.In order to search for promisingly bioactive components,carmichasines A-D were evaluated for cytotoxicity against several human cancer cell lines,but none of them showed significant inhibitory activity.Furthermore,the new diterpenoid alkaloids isolated from Aconitum L.during 2015-2018 were reviewed in Chapter 3,including source,skeletal type and bioactivity.