Studies On The Structures And Bioactivities Of Alkaloids From Four Medical Plants

Alkaloids, a very important group of natural products, are widely distributed in nature including plants, animals and microorganisms, etc. The study of alkaloids is the beginning of the development of natural medicinal chemistry, and is one of the most important research fields in Natural Product Chemistry. Due to their diverse structural features and significant biological properties, alkaloids have always attracted considerable interest from natural products, synthetic, and medicinal chemists, as well as pharmacologists. It is reported that about 1900 skeleton of alkaloids have been obtained from the plants, which are about sixteen percent of the total natural products. Drugs derived from the alkaloids are near fourty-six percent of the total herbal medicinal products, which is nothing comparable to this advantage.In order to find novel secondary metabolites with significant bioactivity from the medical plants, our group studied the isolation, structural elucidation, and biological evaluation of the alkaloids from four medicinal plants including the Ervatamia hainanensis, Lycopodiastrum casurinoides, Palhinhaea cernua and Flueggea suffruticosa in this dissertation.Sixty alkaloids were obtained from the four medicinal plants by using various methods, and their structures were identified as 27 monoterpenoid indole alkaloids,3 quinoline alkaloids,20 lycopodium alkaloids and 10 securinega alkaloids by extensive spectroscopic analysis (NMR, IR, UV, ESIMS, X-ray diffraction and CD), chemical transformations, and computational methods, as well as comparison to known compounds. Fifteeen of them are were identified to be new structures, and compound 51, a novel skeleton, is the first representative of secosecurinega alkaloid bearing an unusual enol moiety from natural source. Moreover, the rest of 14 new compounds are classified as 9 monoterpenoid indole alkaloids (1,7-9,18,24-27) and 5 lycopodium alkaloids (31-32,43,46-47). Compound 1 is a ring-C-contracted ibogan-type monoterpenoid indole alkaloid with an unusual 6/5/6/6/6 pentacyclic rearranged ring system. To the best of our knowledge, only flabelliformidine, previously isolated from Ervatamia flabelliformis Tsiang (Apocynaceae), showed the ring-C-contracted carbon skeleton. Compounds (24-27) possess a nitrogen-containing 9/6 ring system that is rarely found in nature. Moreover, compounds 24 and 25, a pair of epimers, display a 22-nor-monoterpenoid indole alkaloid carbon skeleton, which was only found in deformylstemmadenine, previously isolated from Craspidospermum verticillatum. Compound 47 is the first example of 12,15-epoxy ceruane-type lycopodium alkaloid. Compound 43 is the lycopodium alkaloidal glycoside which was reported for the first time.Moreover, some of these alkaloids were tested for in vitro anti-inflammatory activities, anti-aetylcholinesterase activities and cytotoxicities. The results showed that compound 2 exhibited significant inhibition of lipopolysaccharide (LPS)-induced NO production in RAW 264.7 macrophages with IC50 value of 25.5μM, which was 2-fold higher than that of indomethacin served as positive control with IC50 value of 42.6μM. Moreover, compound 17 showed almost the same inhibition as positive control (indomethacin) with IC50 value of 41.5μM. As far as we know, this is the first report to show that ibogan-type monoterpenoid indole alkaloids, from the Ervatamia genus, exhibit significant anti-inflammatory activities. Compound 31 exhibited moderate anti-aetylcholinesterase activities with IC50 value of 87.3μM. Compound 47 and 49 inhibited A549 cell line with IC50 values of 12.6 and 18.4μM, respectively.Finally, in this dissertation, the new lycopodium alkaloids with potentially useful bioactivities have been reviewed in the period 2005-2015.The results would be a supplement for the researeh on bioactivities of chemical constituents as well as strueture-activity relationship in traditional Chinese medieine, helpful referenee for chemotaxonomy, pharmacology and sereening new medicines, and may benefit utilizing and developing the natural resourees of our country.