Semi-synthesis And Structural Elucidation Of Brevicanines A-D,Four New C₁₉-Diterpenoid Alkaloids With Rotameric Phenomenon From Aconitum Brevicalcaratum

Aconitum was first published in the"Shen Nong's Herbal Classic"and was listed as the defective goods.It is spicy,bitter and poisonous.There are nearly one hundred kinds of A.plants in China as traditional Chinese medicines,such as Chuanwu,Caowu,Fuzi and Bullatine A,and they have anti-inflammatory,analgesic,heat-clearing and detoxifying effects.Studies have shown that diterpenoid alkaloids are the main active constituents and characteristic components of aconitum,which have a wide range of biological activities,especially in the aspects of anti-inflammatory,analgesic and anti-arrhythmia.For many years,diterpenoid alkaloids have been an important source of drug-leading compounds and a research hotspot in botanical classification,which play an important role in lead compound discovery and botanical nomenclature.It can be seen that A.genus has an important medicinal value and is promising.In this paper,diterpenoid alkaloids and their activities were studied from Aconitum brevicalcaratum?Finet et Gagnep.?Diels collected from Lijiang,Yunnan,in order to develop potential medicinal value,the specific work was described below.Separation and purification of diterpene alkaloids from short-headed aconite were proceeded by positive?reverse?phase silica gel column chromatography,medium pressure preparative chromatography and recrystallization,etc.,UPLC-MS,NMR and IR were used to characterize the isolated compounds.Four new C₁₉-diterpenoid alkaloids brevicanines A-D with rotameric phenomenon were isolated from Aconitum brevicalcaratum.They all possessed an unusual axial chiral phenyl-quinazoline side chain and their structures were elucidated by extensive spectroscopic analysis and chemical methods.Meanwhile,brevicanines A and B were semi-synthesized from their parent compound scaconine to further confirm their structures.Variable-temperature NMR spectroscopy was also used to investigate the atropisomers of brevicanine A,in which two sets of signals in ¹H NMR spectra were observed at room temperature and coalesced over 140°C.It is the first research on determining the atropisomeric preference of diterpenoid alkaloids.Additionally,none of them showed potential cytotoxic activity against MCF-7,HCT-116 and HepG-2 in vitro,and did not show good antitumor activity(IC₅₀>50?M,n=3).