Studies On The Chemical Constituents Of Three Southern Plants And On The Stuctural Modification And Structure-Activity Relationship Of Flavonoids

Rhododendron, containing about 850 species, is an important and cosmopolitan genus of the Ericaceae family, distributed in the Northern Hemisphere mainly in Asia. This genus can not only watch, but also apply in traditional medicine to treat various kinds of diseases. For example, the dried stems, leaves and flowers of R. spinuliferum have been used as Chinese folk medicine for eliminating phlegm, relieve cough and anti-asthmatic. The dried leaves of R. dauricum, known in China as’Manshanhong’, were used medicinally as an expectorant and to treat acute and chronic bronchitis. The leaves of R. ellipticum Max is used in Taiwan as a folk medicine to treat high blood pressure.The medicinal properties assigned to Rhododendron prompted us to make a comprehensive and systematic understanding of this genus. The chemical constituents of Rhododendron hainanense Merr which belongs to the Rhododendron genus have not been reported.There are about 100 species in Inula (Compositae) genus, among which over 20 species have been found in China. The flowers of them are used for reducing phlegm and relieving cough as recorded in Chinese Pharmacopoeia. The chemical constituents of Inula hupehensis which belongs to the Inula genus have rare been reported.The genus of Machilus, comprised about 100 species of Lauraceae family. The leaves of Machilus salicina Hance have been used as Chinese folk medicine for detoxification, ears, head pain.However, the chemical compositions of Machilus salicina Hance have never been reported.In order to investgate the medicinal value of these three plants, we carried out the systematic study on chemical constitutents of these plants and biological activities evaluation.About forty constituents have been isolated from aerial parts of Rhododendron hainanense in Hainan Province by means of silica gel column chromatography (CC), preparative thin layer chromatography (PTLC) and recrystallization etc. In combination with the data from literatures, the structures of thirty have been elucidated on the basis of spectroscopic methods (UV, IR, EIMS, HRESIMS,1H- and 13C-NMR.2D NMR (1H-1 HCOSY, HMBC, NOESY) and X-ray diffraction experiments. Among them three compounds are novel. Furthermore the antifungal activities of some flavonoids were also studied. Within the series of flavonoid derivatives tested, farrerol (Rh 2) exhibited excellent inhibitory activities against six plant pathogenic fungi:F. oxysporum f. sp. Niveum, C. gloeosporioides (mango isolate). P. italicum, Rhizoctonia solani, F. oxysporum f. sp. cubense race 4 and Phytophthora melonis. and with EC50 values of 9,18,35,39.5.46 and 66μg/mL.30 compounds were isolated from the petroleum ether part of methanol extracts of I. hupehensis and elucidated as thymols, sesquiterpenoids, flavonoids and steroids in its continuous study, a thymol glycoside is new compound. Moreover the bioactivities of thymols were investigated. Within the series of thymol derivatives tested, compound Ih 3 was the most active, particularly displaying moderate antibacterial activities against Staphylococcus aureus, Methicillin-resistant S. aureus and Escherichia coli with MICs of 62.3,62.8, and 250μg/mL, this compound exhibited inhibitory activities against three plant pathogenic fungi:Rhizoctonia solani, Phytophthora melonis and Peronophythora litchi, with EC50 values of 157,180 and 141 lg/mL.12 compounds were isolated from Machilus salicina,6 compounds were elucidated by published literatures and spectroscopic.Flavonoids are a large class of plant secondary metabolites belonging to the wider family of natural polyphenols and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity.We modified the chemical structure of matteucinol from R. hainanense in attempt to improve its acivity, and synthesized 8-methylflavonoids. "Natraceuticals"’and synthetic flavonoids were evaluated their antimicrobial activities and discussed their structure-activity relationship. Of the compounds tested, compounds 3 and 16 exhibited the strongest inhibitory activity against HL-60 and CMMC-7721 with lower IC50 values of 5.0.27.4; 4.2,32.6μg/mL.