Study On The Chemical Constituents And Bioactivities Of Rhododendron Micranthum, Salvia Cavaleriei And Salvia Deserta

We studied on the chemical constituents and bioactivities of three medical plants Rhododendron micranthum Turcz, Salvia cavaleriei Levl and Salvia deserta Schang, and a total of147compounds, including1new skeleton diterpenoid and33new compounds, have been isolated and identified depending on chromatography methods, spectroscopic and single crystal X-ray diffraction analysis. The chemical type involved monoterpenoid. sesquiterpenoid, nor-sesquiterpenoid, diterpenoid, sesterterpenoid. tritcrpenoid, steroid, coumarin, lignin, flavonoid and other type components. In addition, the immunomodulatory activity,11β-HSD1inhibitory activity and anti-inllammatory activity of some compounds have been investigated.Chapter1. Study on the chemical constituents and bioactivities of R. micranthumR. micranthum (Ericaceae) is widely distributed in Northeast China, North China, Northwest China, Shandong, Henan. Hubei, Hunan and Sichuan provinces of China. Its branches and leaves have been used as a folk medicine in China to treat chronic tracheitis. rheumatism, lumbago, dysmenorrhea, puerperal arthrodynia."Zhaoshanbai Jingao Pian"、a Chinese patent medicine, is a tablet made from the extract of branches and leaves of R. micranthum. We studied on the chemical constituents of R. micranthum leaves and twigs systematically, and investigated on the chemical components of the flowers of this plant for the first time.51compounds have been isolated from the leaves and twigs, and40compounds have been isolated from the flowers. Compound1is a diterpene with new skeleton, and2-15,30,43,52,62and64are new compounds. The absolute configuration of1,2,4,11and12were determined by single crystal X-ray diffraction and ECD spectra. Micranthanone A (1) as the first example of micranthane diterpenoid, represents an important skeleton, and this discovery enriched the structure type of Ericaceae plants. Most of the grayanane diterpenoids are trans-fusion in the A ring and B ring, however, compounds5,6and7are rare cis-fusion. Compound8is the first16-OH acetylized grayanane ditepenoid, and compound14is the first example of6,10-epoxy grayanane diterpenoid. In the bioactivity assay, we test the immunomodulatory activity of the diterpenoids and1β-HSD1inhibitory activity of the triterpenoids isolated from this plant, and compounds54,56,57and59showed significant inhibition against11β-HSD1. In addition, a molecular docking study was performed to clarify the combination of compound57with1β-HSD1.Chapter2. Study on the chemical constituents and bioactivities of S. cavalerieiS. cavaleriei is endemic to China and is distributed in the Guizhou, Sichuan, Guangxi, Guangdong, and Yunnan provinces. The whole plant of S. cavaleriei is used as a Chinese herbal medicine to treat hematemesis, metrorrhagia, dysentery with bloody stools, and traumatic hemorrhage. On the basis of previous work. we further studied on the chemical constituents of this plant.45compounds have been isolated and identified, including8ent-kaurane diterpenes,8abietane diterpenes,1abietane rhamoside,2long-chain diterpenes,14nor-sesquiterpenoids,2steroids,2triterpenes,3lignin glucosides and5other type compounds, and88-95are new compounds. The absolute configuration of88and89were determined by single crystal X-ray diffraction analysis. The inhibitory effects of these compounds on LPS-induced NO production in macro-phage RAW264.7cells were investigated in vitro, and compounds33,94,98,107,108,115and116showed significant inhibitory activity.Chapter3. Study on the chemical constituents of S. desertaS. deserta is a perennial herbaceous plant, and its name also comes from the distribution in Xinjiang gobi desert. The whole plant of S. deserta is used as folk medicine to treat cardiovascular and cerebrovascular diseases.24compounds have been isolated and identified from the acrial part of S. deserta, including3sesterterpenoids,4diterpenoids,8triterpenoids and9other type compounds, and3sesterterpenoids (129-131),1diterpenoids(132) and2triterpenoids(135-136) are new compounds. The absolute configuration of129and130was determined by single crystal X-ray diffraction analysis, and the absolute configuration of131,132, and135were determined on the basis of ECD spectra.