Secondary Metabolites From Laurencia Species And Their Bioactivity And Chemotaxonomic Significance

The marine red algal species of the genus Laurencia (family Rhodomalaceae, order Ceramiales, class Rhodophyceae, and phylum Rhodophyta) comprise about 135 species in the world and more than 20 species distributed in China. They mainly spread along tropical, subtropical, and temperate coasts. The secondary metabolites of the genus Laurencia are mainly composed of sesquiterpenes, diterpenes, triterpenes, and C15-acetogenins, which are usually halogenated and possess antibacterial and cytotoxic activities. In recent ten years, 146 new secondary metabolites with biological activity and structural elucidation were reported from the marine red algae of genus Laurencia, and these were reviewed at the beginning of this dissertation. The isolation, structural elucidation, bioactivity assay, and chemotaxonomic significance of the secondary metabolites of eight Laurencia species including L. mariannensis Yamada, L. decumbens Kützing, L. okamurai Yamada, L. composita Yamada, L. saitoi Perestenko, L. pinnata Yamada, L. tristicha Tseng, Chang, E. Z. Xia et B. M. Xia, and L. similis Nam et Saito were mainly described in this dissertation.Dried and powdered algal material was extracted with organic solvents. Each extract was purified by repeated silica gel and Sephadex LH-20 column chromatography, by preparative thin layer chromatography (PTLC), and by high performance liquid chromatography (HPLC) to yield pure compounds, and their structures were elucidated mainly by 1D and 2D NMR, mass, and infrared spectroscopic techniques. As results, a total of 139 compounds including sesquiterpenes, diterpenes, triterpenes, C15-acetogenins, polybromoindoles, and steroids were isolated and identified from these eight Laurencia species, with 33 new compounds and 6 new natural products. Most of them were halogenated. The new compounds included 17 sesquiterpenes, 4 diterpenes, 2 triterpenes, 5 C15-acetogenins, 4 polybromoindoles, and 1 steroid, and new natural products included 4 sesquiterpenes and 2 isomers of 1-methylcyclohexane-1,4-diols. Briefly, 26 compounds including 8 new structures and 2 new natural products were isolated and elucidated from L. mariannensis, while 20 compounds with 9 new chemicals were identified from L. decumbens. In addition, 9 compounds including 2 new ones were elucidated from L. okamurai, while from L. composita, 30 compounds including 5 new structures and 2 new natural products were characterized. Furthermore, 11 compounds including 7 new structures were isolated and elucidated from L. saitoi, while 9 compounds including 1 new one were isolated and elucidated from L. pinnata. Finally, 18 compounds including 2 new chemicals and 1 new natural product were obtained from L. tristicha, while 16 compounds including 5 new structures and 1 new natural product were isolated and elucidated from L. similis. The isolation of new and unusual structures was a new addition to the molecular diversity of the genus Laurencia, and the isolated precursors and mediators gave new reference to the biogenetical synthesis.Bioactivity assay including antibacterial against Staphylococcus aureus and Escherichia coli, antifungal against Aspergillus niger and Candida albicans, cytotoxic against P388 and HL60 tumor cell lines, and antifeedant against plant pest Spodoptera littoralis showed that some secondary metabolites from these eight Laurencia species, especially those of halogenated structures, possessed antibacterial, antifungal, cytotoxic, and antifeedant activities. The antibacterial activity of polybromoindole LS13 against S. aureus, cytotoxic activity of brominated polyether triterpene LM18 (LD9) against P388 tumor cell line, and antifeedant activity of polyhalogenated chamigrane sesquiterpenes LM2 (LD1, LS8) and LO5 against S. littoralis were notable. A study of structure-activity relationships was accomplished. The result showed that the antibacterial activity of polybromoindoles against S. aureus was influenced by the position of bromines or substituent of methyl. It was futher confirmed that the cytotoxic activity of thyrsiferol-type polyether triterpenes against P388 tumor cell line was affected significantly by its side chain moiety. Enhanced polarity of side chain terminal of thyrsiferol-type polyether triterpenes could reduce their cytotoxic activity against P388 tumor cell line. Hydroxyl and chlorinated vinyl in LM2 (LD1, LS8) and brominated vinyl in LO5 could be the key moieties for antifeedant activity against S. littoralis. The bioactivities and structure-activity relationships provided new evidence for the research of new drug and marine chemical ecology.Chemotaxonomic significance of the halogenated and nonhalogenated secondary metabolites including sesquiterpenes, diterpenes, triterpenes, C15-acetogenins, and indoles from these eight Laurencia species was also discussed. The results indicated that sesquiterpenes, diterpenes, triterpenes, C15-acetogenins, and indoles, especially those of halogenated structures, provided important molecular information for the taxonomy of these eight Laurencia species. Chemotaxonomy based on the secondary metabolites could be an effective complement for the morphological taxonomy of genus Laurencia.