The Study On The Structures Of Microcrystalline Alkaloids From Fritillaria Hupehensis Hsiao Et K.C. Hsia And The LD₅₀ Determination Of Peiminine And Its Five Derivatives

Beimu, Bulbus Fritillariae, is derived from the bulbs of many species of the genus Fritillaria of the Liliaceae. Fritillaria hupehensis Hsiao et K.C. Hsia is a plant growing in the southwest district of Hubei Province, China. And it has been involved in the China Pharmacopoeia.In our study, we got the extraction isolated by alcohol, then with the acid-base method we gain crude alkaloid. Isolating the ointment further by gel column chromatography,we got four new microcrystalline alkaloids and thirteen known alkaloids, among which there are two alkaloids founded from Hubeibeimu firstly. C8 and C9 are new C-nor-D-homo-steroid-Alkaloids of Jervine groups, and their frames of conjugation have been found by the first time in natural products. By spectroscopic analysis (IR,EI-MS,FAB -MS,1H-NMR,13C-NMR,DEPT,1H-1H COSY,HMQC,HMBC,NOESY), the structures of new alkaloids have been established respectively to be (20R, 25S) 5α, 14α-cevanine -3β-actyl -6-one (C1)and (20R, 25S) 5α, 14α-cevanine -3β-actyl -6β-ol ( C3 ) , 5α,17α-17,23-seco-7,12-dien-jervanine-3β,23β-dihydroxy-6-one ( C8 ), 5α,17α-17,23-seco-7,12-dien-jervanine-3β,13α,23β-trihydroxy-6-one(C9). What's more, we rectified the fifth and seventeenth carbon places Of hupehenirine (20S, 25S) 5α,14α,17β-cevanine-6β-hydroxy-3-one.Peminine is the main alkaloid of Fritillaria hupehensis Hsiao et K.C. Hsia, and many Phamacological studies indicate that peminine's antitussive, expectorant and antiasthmatic activity is all very good. We took peminine as a leading compoud, synthetized the (20R, 25S) 5α, 14α-cevanine -3β-actyl -6-one. The structure of it has been established by spectroscopic analysis (FAB -MS,1H-NMR,DEPT and etc. ) On the basis of the pharmacodynamics experiments of Peminine and its five derivatives, we examined the acute dosing toxicity of them. The animals were randomly divided into groups, which were given medicine through ip. Calculate their LD50 and 95% confidence interval by Bliss methods referring to animals'acute morality. The Results are that their LD50 were 14.39, 14.47, 18.41, 23.21, 9.98 mg·kg^-1 in mice respectively, and their toxicities were all lower than peiminine. Therefore, we can drew the conclusion that the five derivatives of peiminine have low toxicity and it is hopeful to find an effective and low-toxicity medicine from those.