Investigation On The Chemical Constituents Of Cordyceps Militaris And Ophiorrhiza Cantoniensis

This dissertation consists of three chapters.The first chapter discussed the second metabolites of wheat fermentation of the medicinal fungi Cordyceps militaris.Then,chapterⅡreported the phytochemical constituents of the plant Ophiorrhiza cantoniensis and their pharmacological activity.Finally,chapterⅢreviewed the latest research progress of natural indole alkaloid glycosides from 2015 to the present.A total of 47 compounds,including thirteen new ones,were isolated from the above two sources by using modern phytochemical separated methods,such as normal phase,molecular sieve filtration,D101 macro reticular resin,and other column chromatography methods.Their structures were determined by comprehensive spectroscopic methods and quantum chemistry calculations,including DFT GIAO ¹³C NMR and ECD calculations.The isolates,included ergosterols,indole alkaloids,cyclopeptides,fatty acids,and other small molecules.In addition,we tested the biological activities of some new compounds.The fungus Cordyceps militaris,belonging to the Clavicipaceae family,is a unique and precious traditional medicine and folk tonic.It has been widely studied for its ability to produce nucleoside antibiotic cordycepin.In the current chemical study,39 compounds,including ten new ones,were obtained from the wheat fermentation culture of C.militairs.The types of compounds involved ergosterols,fatty acids,benzene derivatives,etc.Compounds 1-3 are novel ergosterol derivatives that possess 6/6/6/6/5-pentacyclic skeletons.They might be derived from the normal ergosterol backbone by a[4+2]cycloaddition reaction,while 1 and 2 are further aromatized.Compound 4 is a rare natural sterol with bond-breaking between C-8 and C-14.Compared with the known compound,compound 5 has hydroxyl substitution at C-6.Compounds 6 and 7 have proton substitutions at positions C-4 and C-5,and C-8 and C-9,respectively,comparing with known compounds 25 and 16.Compounds 12、13 and 14、15 represent two pairs of epimers.Compound 19 is ergosterol peroxide.Compound 23 represents a novel framework of ergosterol.Compounds 38 and 39 are novel fatty acid derivatives containing a pyrroloxazinone system.Ophioorhiza plants in the Rubiaceae family have been used as folk medicines to treat different diseases.It has been demonstrated that the genus is rich in indole alkaloids with structural and pharmacological diversities.Ophiorrhiza cantoniensis is a species endemic to our country,mainly distributed in the vast area south of the Yangtze River.In our investigation,eight compounds,including three new ones,were isolated from this species.Compound 2 is an indole alkaloid nitrogen oxide.Compound 4 is a rare indole alkaloid with a novel skeleton.Compounds 1 and 2 showed significant inhibitory activity on Co A-induced T cell proliferation,with IC₅₀values of 23.6μM and 17.9μM,respectively,while compound 1 had an excellent inhibitory effect on LPS-induced B cell proliferation,with an IC₅₀value of 8.7μM.