Studies On The Chemical Constituents Of Five Medicinal Plants

A great number of drugs (ca. 40% of drugs marketed) are directly or indirectly derived from natural products in the last 25 years), indicating that natural products, including secondary metabolite of plant, animal and microorganism, have played a significant role in modern drug researches. As a consequence, medical plants are the rich and vital source for modern drugs. Previous reaserches have reported the isolation of some complex compounds with diverse biological activities from the five medical plants studied in this thesis. Thus, it is meaningful to isolate and identify new compounds by profound chemical studies of these medical plants, which will lay the foundation for further biological activity screening.Five medicinal plants, Lamiophlomis rotata (Benth.) Kudo, Toona ciliata Roem. var. yunnanensis (C. DC.) C. Y. Wu, Chukrasia tabularis var. velutina, Chisocheton paniculatus (Roxb.) Hiern, and Aglaia roxburghiana Miq. have been chemically investigated and their bioactivities have been evaluated. A total of 146 compounds were obtained, which including ten flavonoids, twenty-one iridoids, eight phenylethanoid glucosides, eleven derivatized carbohydrates, thirty-nine limonoids, eighteen triterpenoids, eleven diterpenoids, eleven sesquiterpenoids, and so on. Twenty-four compounds were isolated as new compounds. Some compounds were found active in the tested pharmacological model.Fifty-nine compounds, including ten flavonoids (1-10), twenty-one iridoids (11-31), nine phenylethanoid glucosides (32-39), eleven derivatized carbohydrates (40-50), and nine compounds in other types (51-59) were isolated from L. rotata of the Lamiophlomis genus (Lamiacea). Four iridoids and one derivatized carbohydrate (C13-norisoprenoid derivative) were isolated as new compounds, viz. 6′-O-syringyl-deoxysesamoside (11), 7-dehydroxy-zaluzioside (12), barlerin-6′′-hydroxy-2′′,6′′-dimethylocta-2′′,7′′-dienate ester (13), 6β-n-butoxy-7,8-dehydropenstemonoside (14) and 5β,6α-dihydroxy-3β-(β-D- glucoyranosyloxy)-7-megastigmen-9-one (44). All compounds were screened by luciferase assay, finding that apigenin-7-O-(6″-O-β-D-apiofuranosyl)-β-D-glucopyranoside (3), 6β-n-butoxy-7,8-dehydropenstemonoside (14), 8-epi-7-deoxyloganin (21), 7,8-dehydropenstemonoside (26), andβ-D-glucopyranoside-(2→1)-β-D-glucopyranoside (49) had the desired, apparent NFκB inhibition activities, in a dose-dependant manner in the range of the detection concentration.The medicinal plant often comprises a complex mixture of different phytochemicals (plant secondary metabolites) and these ingredients work"synergistically"for the therapeutic effects. Previous studies have revealed that flavonoids and phenylethanoid glucosides are the main activity components in L. rotata, and the determination of one or two compounds could not give a complete picture of the herb, while quantification of all compounds is extremely difficult. Hence, we chose three flavonoids (apigenin-7-O-β-D-glucopyranoside, luteolin-7-O-β-D-glucopyranoside and luteolin-7-O-β-D-(6″-O-acetyl)-glucopyranoside) and two phenylethanoid glucosides (verbascoside and forsythoside B) as the"marker compounds"that were in large amounts L. rotata. There is no method in analysis of both flavonoids and PhGs of L. rotata in the previous reported methods, this newly developed HPLC-VWD method for simultaneous determination of both flavonoids and PhGs provided much higher specificity, precision and accuracy. By quantification of the five major compounds, the quality of L. rotata could be effectively evaluated initially. Besides, to obtain a full assessment about L. rotata, the analytical method described here is needed to be developed.Twenty-nine compounds, including nine limonoids (60-62, 67-72), eleven diterpenoids (63-66, 73-79), five sesquiterpenoids (80-84) and four compounds in other types (85-88) were isolated from T. ciliata Roem. var. yunnanensis (C. DC.) of the Toona genus (Meliaceae). Three limonoids (toonaciliatins N-P, 60-62) and four pimaradiene-type diterpenoids (toonacilidins A-D, 63-66) were isolated as new compounds. Toonaciliatin N (60), a new limonoid bearing a 1,11-oxygen bridge-1-one moiety, H-2βof which exchanged to D-2βvia a possible enolized intermediate when it was kept in the solvent of CD3OD for about two days, and this was a reversible progress when treated with CH3OH. Toonacilidin A (63) and eudesm-4(15)-ene-1β,6α-diol (83) showed moderate inhibitory activity against H. pylori-SS1 at the level of MIC of 50μg/mL. Compared the limonoids isolated from T. ciliata Roem. var. ciliata and T. ciliata Roem. var. yunnanensis (C. DC.), the latter seems have a more close relationship with T. ciliata than the former. Thus, a proposed biosynthetic map that encompassed all the routes to the isolated limonoids in T. ciliata was successfully applied in T. ciliata Roem. var. yunnanensis (C. DC.), which supported the rationality that they might share a common precursor.Thirty limonoids were isolated from C. tabularis var. velutina of the Chukrasia A. Juss genus (Meliaceae), twenty-nine of which were phragmalin-type limonoids (89-117) except xyloccensin K (118). These phragmalin-type limonoids could be be divided into about six different sub-groups depending on partial structural transformations of the basic phragmalin skeleton, including six 1,8,9-phragmalin-type limonoids (89-93, 99), five 8,9,11-phragmalin-type limonoids (109-113), two 8,9,30- phragmalin-type limonoids (114, 115), thirteen limonoids that possess a biosynthetically extended propionyl or acetyl group at C-15 and a characteristic ketal moiety between the limonoid skeleton and the acyl substituent at C-15 (95-97, 101-108, 116-117), two limonoids with an unprecedented 1,3-dioxolan-2-one formed a pentacyclic carbonate ester (94, 100), and one in other type (118). Nine of these limonoids (velutinasins A-I, 89-97) were isolated as new compounds. Velutinasins A-D (89-92) were a class of C-15-acyl 1,8,9-phragmalin type limonoids, featuring aδ-lactone ring, and theβ-dicarbonyl groups were presented as a relative steabyα-hydroxy-α,β-unsaturated ester system. Velutinasin A (89) comprised a C-16/C-17δ-lactone ring while velutinasins B-D (90-92) comprised C-16/C-30δ-lactone rings. It was the second time to find that class of kinds, and their absolute configurantions were determined by the CD exciton chirality method.Sixteen compounds, including two new apotirucallane-type triterpenoids (119, 120), four known apotirucallane-type (121, 125-127) and four known tirucallane-type (122-124, 128) triterpenoids, four known sesquiterpenoids (129-132) and two known steroids (133, 134) were isolated from C. paniculatus (Roxb.) Hiern of the Chisocheton genus (Meliaceae). The strcture of ghisiamol G (119) was elucidated on the basis of spectroscopic and chemical methods. To the best of our knowledge, this is the first report of a tetracyclic triterpene with a 21,23-lactone ring (ghisiamols G and H, 119 and 120) from the genus Chisocheton.Twelve compounds, including one new tirucallane-type triterpenoids (135), six known tirucallane-type triterpenoids (136-141), one known steroid (142), two known rocaglamides (143, 144) and two known sesquiterpenoids (143, 144) and were isolated from A. roxburghiana Miq.of the Aglaia genus (Meliaceae).Limonoids are secondary metabolites characteristic of the plant family Meliaceae, from which many structurally diversified and chemosystematically significant limonoids have been isolated in the past several decades, attracting people's great interest due to their diverse structures and significant biological activities.Most of the drugs currently in use are chiral compounds, and called chiral drugs. Although they have the same chemical structure, most isomers of chiral drugs exhibit marked differences in biological and pharmacological effects. A limonoid molecule often has at least one asymmetric carbon, which could be recognized as chiral center. As a consequence, assignment of absolute stereochemistry for limonoids is a vital field of research, which is necessary to known their chemical and biological behavior. This article reviews some different techniques used for the assignment of absolute stereochemistry for limonoids in recent years.