Chemistry of bryophytes

CHEMISTRY OF BRYOPHYTES GE XIAOWEI (M.Sc., CHINESE ACADEMY OF PREVENTIVE MEDICINE) A THESIS SUBMITED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMISTRY NATIONAL UNIVERSITY OF SINGAPORE 2007 ACKNOWLEDGEMENTS First of all, I would like to gratefully acknowledge the enthusiastic supervision of Professor Leslie J. Harrison throughout the duration of this project. Without his encouragement and patience, nothing would be possible. Also thanks to Professor Benito C. Tan for identification of the plant materials and many instructions during my research. Several people have been instrumental in allowing this project to be completed. I would like to thank especially Madam Han Yan Hui and Miss Ler Peggy from NMR laboratory, Madam Wong Lai Kwai and Madam Lai Hui Ngee from mass spectrometer laboratory, and Ms Tan Geok Kheng from X-Ray laboratory. Thanks them for their assistance with all types of technical problems at all time. I am also grateful to my friends Dr. Wang Yan Mei, Ms Teo Ee Ling, Zhang Guo Dong, Li Wei, and Huang Ming Xing for their discussions, suggestions and happy hours with them. Thanks to National University of Singapore to award me the research scholarship. Finally, I am forever indebted to my families, my wife, my son, and my parents for their endless understanding, patience, support and love. ii Contents Chapter 1. Introduction 1.1 Natural products in drug discovery 1.2 Natural products in chemical ecology 1.3 New technologies and strategies in natural product studies 1.3.1 New technologies in natural product chemistry 1.3.2 Sources of novel natural products 1.3.3 Biotechnologies in natural product chemistry 11 1.4 Natural products from bryophytes 13 1.4.1 Natural products from Mosses 14 1.4.2 Natural products from liverworts 21 Chapter 2. Natural products from some moss species 24 2.1 Suborder Dicranineae Fleisch 26 2.1.1 Family Dicranaceae, Dicranoloma blumii (Nees) Par. and Dicranoloma assimile (Hampe) Par. 26 2.1.2. Family Leucobryaceae, Leucobryum sanctum (Brid.) Hampe 39 2.2 Suborder Leucodontineae, Family Neckeraceae, Himantocladium cyclophyllum (C. Müll) Fleich 44 2.3 Suborder Hypnineae 54 2.3.1 Family Hypnaceae, Ectropothecium sparsipilum (Bosch & Lac.) Jaeg iii 54 2.3.2 Family Hylocomiaceae, Rhytidiadelphus squarrosus (Hedw.) Wasmst 58 2.4 Suborder Grimmiineae, Family Grimmiaceae, Racomitrium lanuginosum (Hew.) Brid. 61 2.5 Suborder: Bryineae, Family Rhizogoniaceae, Pyrrhobryum spiniforme (Hedw.) Mitt. and Suborder Hypnineae, Family Hylocomiaceae, Pleurozium schreberi (Brid.) Mitt. 67 2.6 Order: Polytrichales, Family Polytrichaceae, Polytrichum commune Hedw 72 2.7 Conclusions 81 Chapter 3. Natural products from some liverwort species 83 3.1 Jungermanniidae 85 3.1.1 Riccardia crassa (Schwaegr.) C. Massal, Riccardia elata (Steph.) Schiffn., and Riccardia graeffei (Steph.) Hewson 85 3.1.2 Unidentified Malaysian Bazzania species 100 3.1.3 Lepidozia chordulifera Lindenb 107 3.1.4 Ptychanthus striatus (Lehm. & Lindenb.) Nees 116 3.1.5 Blepharostoma trichophyllum (L.) Dumort 123 3.1.6 Balantiopsis erinacea (Tayl.) Mitt 136 3.1.7 Cryptochila grandiflora (Lindenb. & Gott.) Grolle 143 3.2 Marchantiidae 154 3.2.1. Preissia quadrata (Scop.) Nee 154 3.3 Conclusion 159 iv Chapter Chemosystematics of mosses and liverworts 160 References 164 v SUMMARY In this thesis, the chemistry of twenty-four bryophyte species has been studied. A combination of chromatographic methods was used to isolate thirty-seven new and thirtyfour known compounds. The structures of these compounds were elucidated using a combination of techniques, such as NMR, MS, XRD, and chemical modifications. These compounds include flavonoids, terpenoids, bibenzyls, simple phenolic compounds, and some very specific aromatic compounds. Chapter One briefly introduces the background of this project including natural products in ecology and drug discovery. New technologies and strategies in natural product studies, such as LC-NMR, Computer-Assisted Structure Elucidation (CASE) systems, new sources of natural products such as One Strain–Many Compounds (OSMAC), biotransformation, and some biochemistry methods, are also outlined. Finally, the natural products from bryophytes are described. Chapter Two mainly includes the chemical studies of ten moss species from which seventeen new and ten known compounds were isolated. Phenanthrene derivatives, such as dicranopyran (10-hydroxy-5-methoxy-2,2-dimethyl-2H-phenanthro[4,3-b]pyran) and another five similar compounds, were found in Dicranoloma blumii and Racomitrium lanuginosum. Ohioensins, pallidisetin A [(9E)-2,3-dihydro-2-phenyl-5-styrylchromen-4one], pallidisetin B (2,3-dihydro-2-phenylnaphtho[2,1-f]chromen-4-one), and communin A [(9Z)-2,3-dihydro-2-phenyl-5-styrylchromen-4-one] were isolated from Polytrichum commune. Himantocladium cyclophyllum vi produced the unique biflavonoid himantoflavone, which contained one flavone moiety and one isoflavone moiety. 3′,3′′′Binaringenin methyl ethers were obtained from Ectropothecium sparsipilum. Pyrronin (5phenyl-5H-naphtho[1,2-c]-chromene-1,3-diol) was found in Pyrrhobryum spiniforme and Pleurozium schreiberi and leuconin [4,7,9-trihydroxy-1-(4-hydroxyphenyl)-6H-anthra[1,9-bc]-furan-6-one] was isolated from Leucobryum sanctum. Chapter Three is concerned with twenty new and twenty-four known compounds from ten liverwort species. Most of them are terpenoids, flavonoids, and bisbibenzyls. Two bisbibenzyl acids, blepharonins A and B from Blepharostoma trichophyllum and three chlorinated bisbibenzyls (2,10,12,6',14'-pentachloroisoplagiochin C, 2,12,14'- trichloroisoplagiochin C-1'-methyl ether, 2,10,12,14'-tetrachloroisoplagiochin C-1'methyl ether) from Lepidozia chordulifera are the most interesting compounds. Chapter Four briefly discusses the use of the chemistry of bryophytes in taxonomy. The results showed that the chemistry of bryophytes could provide taxonomic supporting information at class or subclass level. vii List of Tables Table 1-1, Biflavonoids from Moss Species Table 2-1, The classification of Bryopsida Table 2-2, 1H, HMBC, NOESY and 13C NMR data for compound 89 Table 2-3, 1H, HMBC, NOESY and 13C NMR data for compound 92 Table 2-4, 1H, HMBC, NOESY and 13C NMR data for compound 93 Table 2-5, 1H, HMBC, NOESY and 13C NMR data for compound 94 Table 2-6, 1H, HMBC, and 13C NMR data for compound 95 Table 2-7, 1H, HMBC, and 13C NMR data for compound 99 Table 2-8, 1H, HMBC, and 13C NMR data for compound 105 Table 2-9, 1H, HMBC, and 13C NMR data for compound 107 Table 2-10, 1H, HMBC, and 13C NMR data for compound 109 Table 2-11, 1H, HMBC, NOESY and 13C NMR data for compound 110 Table 2-12, 1H, HMBC, NOESY and 13C NMR data for compound 111 Table 3-1, The classification of Hepatophyta Table 3-2, 1H, HMBC, and 13C NMR data for compound 133 Table 3-3, 1H, HMBC, and 13C NMR data for compound 164 Table 3-4, 1H, HMBC, and 13C NMR data for compound 176 Table 3-5, 1H, HMBC, and 13C NMR data for compound 177 Table 3-6, 1H, HMBC, and 13C NMR data for compound 178 Table 3-7, 1H, HMBC, and 13C NMR data for compound 191 Table 3-8, 1H, HMBC, and 13C NMR data for compound 200 viii Table 3-9, 1H, HMBC, and 13C NMR data for compound 226 Table 3-10, 1H, HMBC, and 13C NMR data for compound 228 Table 3-11, 1H, HMBC, and 13C NMR data for compound 229 Table 3-12, 1H, HMBC, and 13C NMR data for compound 230 ix List of Figures Figure 1-1, Overview of isoprenoid biosynthesis and compartmentation in plants Figure 2-1, Taxonomy of studied moss species Figure 2-2, Selective HMBC correlations of 89 Figure 2-3, Selective HMBC correlations of 92 Figure 2-4, Selective HMBC correlations of 93 Figure 2-5, Selective NOE effects of 93 Figure 2-6, Selective HMBC correlations of 94 Figure 2-7, Selective NOE effects of 94 Figure 2-8, Selective HMBC correlations of 95 Figure 2-9, Selective HMBC correlations of 99 Figure 2-10, Selective NOE effects of 100 Figure 2-11, Selective HMBC correlations of 104 Figure 2-12, Selective NOE effects of 101, 102 and 103 Figure 2-13, Selective HMBC correlations of 107 Figure 2-14, Selective HMBC correlations of 109 and 110 Figure 2-15, Selective NOE effects of 109 and 110 Figure 2-16, Selective HMBC correlations of 111 Figure 3-1, Taxonomy of studied liverwort species Figure 3-2, Selective HMBC correlations and relative configuration of 133 Figure 3-3, Relative configuration and selective NOE effects of 135 Figure 3-4, Selective HMBC correlations of 164 x Chapter Chemosystematics of mosses and liverworts Chemosystematics was defined as the classification of organism based on the biochemical level. Nowadays, more and more natural product chemists are interested in bioactive compounds with pharmaceutical or agrochemical uses. Only a few scientists keep working to find the ecological roles of natural products. Some of them try to make clear the correlations between the distributions of natural products and the taxonomic treatment of the species investigated [170]. Scientists estimate that about a quarter of the total plant 20000 to 60000 genes are responsible for encoding enzymes for secondary metabolites [171] . These enzymes that produce secondary metabolites probably have evolved – initially by accident – from enzymes used in primary metabolism, but were genetically fixed when they acquired some useful ecological function advantageous to the producing organism. That’s the reasons plant species have their specific secondary metabolites. Meanwhile, most of the genes, whether formed by duplication or not, will have evolved very slowly. During the course of hundreds of millions of years of evolution they resulted in a gigantic number of new secondary products. However, in some cases they may have been abrupt major changes, resulting in very different enzymes and novel types of compounds. By studying chemosystematics, scientists may reveal the evolution process of plants. The results of chemosystematics can also be used to show the economic value of threatened plants, provide the tools to identify rare and endangered species, and indicate alternative plant 160 sources of valuable medicinal drugs that contain the same or similar active ingredients [172] . After more and more secondary metabolites were isolated from bryophyte species, people started to study the chemosystematics of this type of plant. In the secondary metabolites from bryophyte, flavonoids are very common and widely distributed in bryophyte species. Scientists from Germany studied the flavonoid contents of 160 moss species from 73 genera and 500 liverwort species from 143 genera by 2D-TLC. Results indicated that there was no solid base for chemotaxonomic evaluations with flavonoids as marker compounds at the order, family or genus level of moss species. For liverwort, it is valid only at the family, genus and species level [173] . Japanese scientists also summarized the chemistry of bryophytes and discussed the chemosystematics [164] . Reviews about the chemistry of bryophytes have been published every few years [174, 175]. The chemistry of bryophyte has provided some useful information. The characteristic secondary metabolites from liverwort include a diversity of terpenoids and the exclusive compound bisbibenzyl. Mosses contain biflavonoids and some other novel aromatic compounds. These results correspond to the physiological character of them. As mentioned above, liverworts have many oil bodies that contain large quantities of terpenoids. Less terpenoid was found in mosses because of absence of oil bodies. This is the difference at the class level. However at the lower levels, no positive conclusion can be made up to now. 161 Bisbibenzyls are one group of the characteristic compounds from liverworts. This type of compound is mainly distributed in the liverwort species which belong to subclass Jungermanniidae order Jungermanniales. However it was also found in the species which are under other orders and subclass Marchantiidae. Recently chlorinated bisbibenzyls are frequently isolated from liverwort species belonging to different orders under subclass Jungermanniidae. Their distribution cannot afford any further taxonomic supports either at family or genus levels. Compared to that of liverwort, the chemistry of moss is less diverse. On the other hand, some moss species contain very specific compounds, such as ohioensins from Polytrichum. These species may have faced abrupt environmental changes to result in very different enzyme and secondary metabolites. In conclusion, the chemistry of bryophyte can only provide taxonomic supporting information at class or subclass level. There are many reasons. Firstly, because of the difficulties in obtaining enough plant materials, scientists cannot study the bryophyte species systematically and extensively. No reporting about some secondary metabolites in other orders or families may attribute to the inaccessibility of plant materials. Secondly, different environmental conditions can lead to several chemotypes for one species. To obtain enough plant materials, some species are even needed to be cultured axenically in lab. Under different living conditions, same species may activate different enzyme system to produce different compounds. This increases the complexities of chemosystematics. Thirdly, the collection time of the studied species may vary from a few days to a few years. The secondary metabolites may change due to exposure to light or heat during the storage. Fourthly, different parts of plant may contain different 162 compounds. During the discovery of anti-malaria compound quinine from plant Cinchona, scientist found that alkaloid level is highest in young leaves. These alkaloids are of cinchophylline-type (242), semidimeric indole alkaloids, which are quite different from the quinolines (243) presenting in the bark [176] . Bryophytes are usually very tiny and not easy to separate fresh and mature parts. Because of the problems mentioned above, chemosystematics cannot provide much useful information to the taxonomy of bryophytes at the lower levels up to now. H3CO N N H H H HN H HO H H N H H3CO OCH3 242 N 243 163 N References: 1. Fraenkel, G. S., Science, 1959, 129, 1466. 2. Harborne, J. B., Nat. Prod. Rep., 2001, 18, 361. 3. Thomas, R., Nat. Prod. Rep. 2004, 21, 224. 4. Schwarze, D. M., Chemical Ecology of Vertebrates, Cambridge University Press, 2006. 5. Eisner, T., and Meinwald, J., Chemical Ecology, The Chemistry of Biotic Interaction, National Academy Press, 1995. 6. Iken, K., and Baker, J. B., J. Nat. Prod., 2003, 66, 888. 7. Wright, C. W., Phytochemistry. Rev., 2005, 4, 55. 8. Oberlies, N. H. and Kroll, D. J., J. Nat. Prod., 2004, 67, 129 9. Ireland C. M., Aalbersberg W., Andersen, R. J., Semiramis A.-K., Berlinck, R. G. S., Bernan, V., Carter, G., Churchill, A. C. L., Clardy, J., Concepcion, G. P., Silva, E. D. E., Discafani, C., Fojo, T., Frost, P., Gibson, D., Greenberger, L. M., Greenstein, M., Harper, M. K., Mallon, R., Loganzo, F., Nunes, M., Poruchynsky M. S., and Zask, A., Pharmaceut. Biol., 2003, 41, supplement, 15. 10. Singh, S. B., and Barrett J. F., Biochem. Pharmacol., 2006, 71, 1006. 11. Newman, D. J., Cragg, G. M., and Snadder, K. M., J. Nat. Prod., 2003, 66, 1022. 12. Exarchou, V., Krucker, M., Beek, T. A. V., Vervoort, J., Gerothanassis, I. P., and Albert, K., Mag. Reson. Chem., 2005, 43, 681. 13. Wolfender, J. L., Queiroz, E. F., and Hostettman, K., Mag. Reson. Chem., 2005, 43, 697. 14. Exarchou, V., Godejohann, M., Beek, T. A. V., Gerothanassis, I. P., and Vervoort, J., 164 Anal. Chem. 2003, 75, 6288. 15. Lambert, M., Stærk, D., Hansen, S., H., Sairafianpour, M., and Jaroszewski, J. W., J. Nat. Prod. 2005, 68, 1500. 16. Clarkson, C. Stærk, D., Hansen, S., H., Smith, P. J., and Jaroszewski, J. W., J. Nat. Prod. 2006, 69, 527. 17. Steinbeck, C., Nat. Prod. Rep. 2004, 21, 512. 18. Kashman, Y., Gustafson, K. R., Fuller, R. W., Cardellina, J. H., Mcmahon, J. B., Currens, M. J., Buckheit, R. W., Hughes, S. H., Cragg, G. M., and Boyd, M. R., J. Med. Chem., 1992, 35, 2735. 19. Cox, P. A., Pharma. Biol, 2001, 39, Supplement, 33. 20. Cragg, G. M., and Newman, D. G., Pure Appl. Chem., 2005, 77, 7. 21. Hostettmann, K., Wolfender, J.-L., and Terreaux, C., Pharma. Biol, 2001, 39, Supplement, 18. 22. Hanjani, S. A., Stagliano, N. E., Yamada, M., Huang, P. L., Liao, J. K., and Moskowitz, M. A., Stroke, 2001, 32, 980. 23. Whatman, M., and Altmann, K. H., Curr. Med. Chem. Anti-Cancer Agents, 2002, 2, 123. 24. Kaeberlein, T., Lewis, K., and Epstein, S. S., Science, 2002, 296, 1127. 25. Strobel, G. A., Microb. Infect., 2003, 5, 535. 26. Sipkema, D., Franssen, M. C. R., Osinga, R., Tramper, J., and Wijffels, R. H., Mar. Biotechnol., 2005, 7, 142. 27. Cueto, M., Jensen, P. R., Kauffman, C., Fenical, W., Lobkovsky, E., and Clardy, J., J. Nat. Prod., 2001, 64, 1444. 165 28. Hwang, Y., Rowley, D., Rhodes, D., Gertsch, J., Fenical, W., and Bushman, F., Mol. Pharmacol. 1999, 55, 1049. 29. Chinworrungsee, M., Kittakoop, P., Isaka, M., Rungrod, A., Tanticharoen, M., and Thebtaranonth, Y., Bioorg. Med. Chem. Lett., 2001, 11, 1965, 30. Caro, E., Starks, C. M., Jensen, P. R., Fenical, W., Lobkovsky, E., and Clardy, J., J. Nat. Prod., 2003, 66, 423. 31. Bode, H. B., Bethe, B., Höfs, R., and Zeeck, A., Chembiochem, 2002, 3, 619. 32. Duztz, W. A., Houwmeester, H., Berlin, J. B. V., and Witholt, B., Appl. Microbio. Biotechnol. 2003, 61, 269. 33. Noma, Y., Yamasaki, S., and Asakawa, Y., Phytochemistry, 1992, 31, 2925. 34. Chang, H. C., and Oriel, P., J. Food Sci., 1994, 59, 660. 35. Cane, D. E., Walse, C. T., and Khosla, C. Science, 1998, 282, 63. 36. Griffith, B. R., Langenhan, J. M., and Thorson, J. S., Curr. Opinion Biotech., 2005, 16, 622. 37. Bowels, D., Isayenkova, J., Lim, E-K, and Poppenberger, B. Curr. Opinion Plant Biol., 2005, 8, 254. 38. Zinsmeister, H.D., Becker, H., and Eicher, T. (1991). Angew. Chem. , Int. Ed. Engl., 1991, 30, 140. 39. Pearson L. C. The Diversity and Evolution of Plants, CRC Press, 1995, 402. 40. Connolly, J. D., Stud. Org. Chem., 1985, 20, 3. 41. Zinsmeister, H. D., Becker, H., Eicher, T., Angew. Chem. Int. Ed. Engl. 1991, 30, 130. 42. Asakawa, Y., Phytochemistry, 2004, 65, 623. 43. Qiu, Y. L., Cho, Y., Cox, J. C., and Palmer, J. D., Nature, 1998, 394, 671. 166 44. Read, D. J., Duckett, J. G., Francis, R., Ligrone, R., and Russell, A., Phil. Trans. R. Sco. Lond. B, 2000, 355, 815. 45. Anhut, S., Seeger, T., Zinsmeister, H. D., and Geiger, H., Z. Naturforsch, 1989, 44c, 189. 46. Anhut, S., Seeger, T., Biehl, J., Zinsmeister, H. D., and Geiger, H., J. Hattori. Bot. Lab., 1989, 67, 377. 47. Geiger, H., Anhut, S., and Zinsmeister, H. D., Z. Naturforsch, 1988, 43c, 1. 48. Pampendahl, C., seeger, T., Geiger, H., and Zinsmeister, H. D., Phytochemistry, 1996, 42, 1621. 49. Brinkmeier, E., Geiger, H., and Zinsmeister, H. D., Phytochemistry, 1999, 52, 297. 50. Becker, H., Mues, R., Zinsmeister, H. D., Herzog, F., and Geiger, H., Z. Naturforsch, 1986, 41c, 507. 51. Seeger, T., Zinsmeister, H. D., and Geiger, H., Z. Naturforsch, 1990, 45c, 583. 52. Geiger, H., and Markham, K. R., Phytochemistry, 1992, 31, 4325. 53. Zinsmeister, H. D., Weyand, J., Voigt, A., Seeger, T. and Geiger, H., Z. Naturforsch., 1996, 51c, 781. 54. Markham, K. R., Andersen, Ø. M., and Viotto, E. S., Phytochemistry, 1988, 27, 1745. 55. Lindberg, G., Ősterdahl, B.-G., and Nilsson, Chem. Scripta., 1974, 5, 140. 56. Ősterdahl, B.-G., Acta. Chem. Scand. 1983, B37, 69. 57. Seeger, T., Geiger, H. and Zinsmeister, H. D., Phytochemistry. 1991, 30, 1653. 58. Geiger, H., and Bokel, M., Z. Naturforsch., 1989, 44c, 559. 59. Brinkmeier, E., Geiger, H., and Zinsmeister, H.D., Z. Naturforsch., 1998, 53, 1. 60. Seigel, U., Zinsmeister, H. D., and Stein, W., J. Hattori. Bot. Lab., 1989, 67, 389. 167 61. Stein, W., and Zinsmeister, H. D., J. Hattori. Bot. Lab., 1991, 69, 195. 62. Sievers, H., Burkbardt, G., Becker, H, and Zinsmeister, H. D., Phytochemisty, 1992, 31, 3233. 63. Sievers, H., Burkbardt, G., Becker, H, and Zinsmeister, H. D., Phytochemisty, 1994, 35, 795. 64. Seeger, T., Geiger, H., Zinsmeister, H. D., and Rozdzinski, W., Phytochemistry. 1993, 34, 295. 65. Geiger, H., and Seeger, T., Z. Naturforsch., 2000, 55c, 870. 66. Seeger, T., Geiger, H., Zinsmeister, H. D., Frahm, J.-P. and Witte, L., Z. Naturforsch. 1992, 47c, 667. 67. Brinkmeier, E., Geiger, H., and Zinsmeister, H. D., Z. Naturforsch., 2000, 55c, 866. 68. Lopez-Saez, J. A.; Perez-Alonso, M. J.; Velasco-Negueruela, A. Ars Pharmaceutica, 1996, 37, 83. 69. Rudolph, H., Vaduz: J. Cramer, 1978, 13, 279. 70. Vowinkel, E., Chem. Ber., 1975, 108, 1166. 71. Mentlein, R., and Vowinkel, E, Liebigs Ann., Chem. 1984, 1024. 72. Bouvier, F., Rahier, A., and Camara, B., Prog. Lip. Res., 2005, 44, 357. 73. Vitt D. H., New Manual of Bryology, Hattori Botanical Lab, 1984, p 696-760. http://www.science.siu.edu/landplants/Bryophyta/Mosses.Vitt.html 74. Tan, B.C. and Koponen, T., Acta Bot. Fennici., 1983, 20, 317. 75. Klazenga, N., J. Hattori Bot. Laboratory., 1999, 87, 1. 76. Ichikawa, T., Yamada, K., Namikawa, M., Sakai, K., and Kondo, K., J. Hattori Bot. Laboratory., 1984, 56, 209. 168 77. Matsuo, A., Uto, S., Nakayama, M., and Hayashi, S., Tetrahedron Lett. 1976, 28, 2541. 78. Matsuo, A., Yuki, S. and Nakayama, M., J. Chem. Soc. Perkin Trans., 1986, 1, 701. 79. Leong, Y.-W., Kang, C.-C., Harrison, L. J., and Powell, A. D., Phytochemistry, 1997, 44, 157-165. 80. Asakawa, Y., Hashimoto, T., Takikawa, K., Tori, M. and Ogawa, S., Phytochemistry, 1991, 30, 235. 81. Asakawa, Y., Toyota, M., and Takemoto, T., Phytochemistry, 1978, 17, 2005. 82. Asakawa, Y., Kusube, E., Takemoto, T., and Suire, C., Phytochemistry, 1978, 17, 2115. 83. Asakawa, Y., Takeda, R., Toyota, M., and Takemoto, T., Phytochemistry, 1981, 20, 858. 84. Asakawa, Y., Takikawa, K., Toyota, M., and Takemoto, T., Phytochemistry, 1982, 21, 2481. 85. Marsili, A., Morelli, I., Bernardini, C., Pacchiani, M., Phytochemistry 1972, 11, 2003. 86. Hansen, C. E.; Rossi, P., Phytochemistry 1991, 30, 1837. 87. Cox, R.H., Spectrochlmlea Acta, 1969, 25A, 1189. 88. Pearce, I. S. K., Woodin, S. J., van der Wal, R., New Phytol., 2003, 160, 145. 89. Jones, M. L. M., Oxley, E. R. B., Ashenden, T. W., Environ. Pollut., 2002, 120, 371 90. Baddeley, J. A., Thompson, D. B. A., Lee, J. A., Environ. Pollut., 1994, 84, 189. 91. Vandekerkhove, O., Z. Pflanzenphysiol., 1980, 100, 369. 92. Czeczuga, B., Bryologist, 1980, 83, 21. 93. Karunen, P., Aro, E. M., Physiol. Plantarum, 1979, 45, 265. 169 94. Karunen, P., Bryologist, 1977, 80, 313. 95. Karunen, P., Bryologist, 1978, 81, 100. 96. Nissinen, R., and Sewón P., Phytochemistry, 1994, 37, 179. 97. Jung, M., Zinsmeister, H. D., and Geiger, H., Z. Naturforsch. 1994, 49c, 697. 98. Zheng,G. Q., Chang, C. J., Stout, T. J., Clardy, J. and Cassady, J. M., J. Am. Chem. Soc., 1989, 111, 5500. 99. Zheng,G. Q., Chang, C. J., Stout, T. J., Clardy, J., Ho, D. K. and Cassady, J. M., J. Org. Chem., 1993, 58, 366. 100. Zheng, G. Q., Ho, D. K., Elder, P. J., Stephens, R. E., Cottrell, C. E., and Cassady, J. M., J. Nat. Prod. 1994, 57, 32. 101. Crandall-Stotler, B., and Stotler, R., Bryophyte Biology, Cambridge University Press, Cambridge, 2000, 21 102. Schuster R. M., Bryophyte Systematics. Academic Press, London and New York. 1979, p 41-82. 103. Das, V. S. R., and Rao, M. P., Nature, 1963, 198, 4884. 104. Hwa, B. S., Phipps, R. K., and Perry, N. B., J. Nat. Prod, 2004, 67, 718. 105. Yoshida, T., Toyota, M., and Asakawa, Y., J. Nat. Prod, 1997, 60, 145. 106. Nagashima, F., Momosaki, S., Watanabe, Y., Toyota, M., Huneck, S., and Asakawa, Y., Phytochemistry, 1996, 41, 207. 107. Nagashima, F., Sari, Y., Tori, M., Asakawa, Y., and Huneck, S, Phytochemistry, 1993, 34, 1341. 108. Asakawa, Y., Toyota, M., Takeda, R., Suire, C., and Takemoto, T., Phytochemistry, 1981, 20, 725. 170 109. Toyota, M., and Asakawa, Y., Phytochemistry, 1993, 32, 137. 110. Perry, N. B., and Foster, L. M., J. Nat. Prod., 1995, 58, 1131. 111. Baldoqui, D. S., Kato, M. J., and Cavalheiro, A. J., Phytochemistry, 1999, 51, 899. 112. Maxwell, A., and Rampersad, D., J. Nat. Prod., 1988, 51, 370. 113. Ali, A. A., and Kondo, K., Chem. Pharm. Bull., 1992, 40, 1130. 114. Nagarajian, G. R., and Parmar, V. S., Planta Med., 1977, 32, 3. 115. Ng, A. S., Phytochemistry, 1988, 27, 3708. 116. Gupta, K. K., and Taneja, S. C., Phytochemistry, 1983, 22, 314. 117. Pantichpol, K. and Waterman, P. G., Phytochemistry, 1978, 17, 1363. 118. Fries, R., Die Naturlichen Pflanzenfamilien 2nd. Edn., Duncker & Humbolt, Berlin, 1959, 17A. 119. Escarria, S., Torrenegra, R. D., and Angarita, B., Phytochemistry, 1977, 16, 1618. 120. Koh, L. L., and Ng, A. S., Acta Cryst, 1993, C49, 105. 121. Pinar, M., Phytochemistry, 1973, 12, 3014. 122. Lu, R. H., Paul, C., Basar, S., König, W. A., Hashimoto, T., and Asakawa, Y., Phytochemistry, 2003, 63, 581. 123. Toyota, M., Asakawa, Y., and Takemoto T., Phytochemistry, 1981, 20, 2359. 124. Wu, C-L, and Chang, S-J, Phytochemistry, 1992, 31, 2150. 125. Wu, C-L, and Chen, C-L, Phytochemistry, 1992, 31, 4213. 126. Toyota, M., and Asakawa, Y., Phytochemistry, 1988, 27, 2155. 127. Nagashima, F., Momosaki, S., Watanabe, Y., Takaoka, S., Huneck, S., and Asakawa, Y., Phytochemistry, 1996, 42, 1361. 128. Warmers, U., and Konig, W. A., Phytochemistry, 1999. 52, 99. 171 129. Tori, M., Toyota, M., Harrison, L. J., Takikawa, K, and Asakawa, Y., Tetrahedron Lett., 1985, 26, 4735. 130. Martini, U., Zapp, J., and Becker, H., Phytochemistry, 1998, 47, 89. 131. Ratcliffe, R. W., Org. Synth., 1976, 55, 84. 132. Cullmann, F., Schmidt, A., Schuld, F, Trennheuser, M. L., and Becker, H., Phytochemistry, 1999, 52, 1647. 133. Matsuo, A., Kubota, N., Nakayama, M., and Hayashi, S., Chem. Lett. 1981, 1097. 134. Matsuo, A., Uto, S., Nozaki, H., and Nakayama, M., J. Chem. Soc., Perkin Trans I, 1984, 215. 135. Matsuo, A., Nozaki, H., Kubota, N., Uto, S., and Nakayama, M., J. Chem. Soc., Perkin Trans I, 1984, 203. 136. Shu, Y. F., Wei, H. C., and Wu, C. L., Phytochemistry, 1994, 37, 773. 137. Toyota, M., Nakaishi, E., and Asakawa, Y., Phytochemistry, 1996, 41, 833. 138. Paul, C., König, W. A., and Wu, C. L., Phytochemistry, 2001, 58, 789. 139. Anton, H., Kraut, L., Mues, R., and Morales Z. M. I., Phytochemistry 1997, 46, 1069. 140. Hashimoto, T., Irita, H., Takaoka, S., Tanaka, M., and Asakawa, Y., Tetrahedron 2000, 56, 3153. 141. Hertewich, U. M., Zapp, J., and Becker, H., Phytochemistry 2003, 63, 227. 142. Scher, J. M., Zapp, J., Schmidt, A., and Becker, H., Phytochemistry 2003, 64, 791. 143. Seung, H. B., Phipps, R. K., and Perry, N. B., J. Nat. Prod. 2004, 67, 718. 144. Hashimoto, T., Takaoka, S., Tanaka, and Asakawa, Y., Heterocycles, 2003 59, 645. 145. Wu, C-L, Wang, C-J, and Yin, M-H, J. Chin. Chem. Soc., 2001, 48, 241. 172 146. Hashimoto, T., Horie, M., Takaoka, S., Tori, M., and Asakawa, Y., Chem. Lett., 1995, 481. 147. Hashimoto, T., Horie, M., Toyota, M., Taira, Z., Takeda, R., Tori, M., and Asakawa, Y., Tetrahedron Lett. 1994, 35, 5457. 148. Hashimoto, T., Ikeda, H., Takaoka, S., Tanaka, M., and Asakawa, Y., Phytochemistry, 1999, 52, 501. 149. Nagashima, F., Sekiguchi, T., Takaoka, S., and Asakawa, Y., Chem. Pharm. Bull., 2004, 52, 556. 150. Mues, R., J. Hattori Bot. Lab. 1982, 53, 271. 151. Feld, H., Zapp, J., Connolly, J. D., and Becker, H., Phytochemistry, 2004, 65, 2357. 152. Labbé, C., and Faini, F, Villagrán, C., Coll, J., and Rycroft, D. S., J. Agric. Food Chem. 2005, 53, 247. 153. Asakawa, Y., Takikawa, K., Tori, M., and Campbell, E. O., Phytochemistry, 1986, 25, 2543. 154. Buchanan, M. S., Connolly, J. D., Kadir, A. A., and Rycroft, D. S., Phytochemistry, 1996, 42, 1641. 155. Connolly, J. D., Harding, A. E., and Thornton, I. M. S., J. C. S. Chem. Comm., 1972, 1320. 156. Andersen, N. H., and Huneck, S. Phytochemistry, 1973, 12, 1818. 157. Andersen, N. H., Costin, C. R., JR, Kramer, C. M., Ohta, Y., and Huneck, S., Phytochemistry, 1973, 12, 2709. 158. Matsuo, A., Nozaki, H., Nakayama, M., Hushi, Y., and Hayashi, S., Tetrahedron. Lett. 1975, 4, 241. 173 159. Andersen, N. H., Bissonette, P., Liu, C.–B., Shunk, B., Ohta, Y., Tseng, W. C. L., Moore, A., and Huneck, S., Phytochemistry, 1977, 16, 1731. 160. Ohta, Y., Andersen, N. H., and Liu, C.–B., Tetrahedron, 1977, 33, 617. 161. Andersen, N. H., Ohta, Y., Moore, A., and Tseng, W. C. L., Tetrahedron, 1978, 34, 41. 162. Hardt, I. H., Rieck, A., König, W. A., and Muhle, H., Phytochemistry, 1995, 40, 605. 163. König, W. A., Bülow, N., Fricke, C., Melching, S., Rieck, A., and Muhle, H., Phytochemistry, 1996, 43, 629. 164. Asakawa, Y., Progress in the Chemistry of Organic Natural Products 65, SpringerVerlag, 1995, p308-311. 165. Razdan, M. K., Introductin to Plant Tissue Culture, Second Edition, Science publisher, Inc. 2003, p1-18. 166. Asakawa, Y., Toyota, M., Taira, Z., Takemoto, T., and Kido, M., J. Org. Chem., 1983, 48, 2164. 167. Tori, M., Masuya, T., and Asakawa, Y., J. Chem Research (S), 1990, 36. 168. Mahato, S. B., and Mukherjee, S., Phytochemistry, 1985, 23, 2131. 169. Friederich, S., Maier, U. H., Neumann, B. D., Asakawa, Y., and Zenk, M. H., Phytochemistry, 1999, 50, 589 170. Harborne, J. B., and Turner, B. L., Plant Chemosystematics, Academic Press, 1984, 4. 171. Pichersky, E., and Gang, D. R., Trends in Plant Science, 2000, 5, 439. 172. Grayer, R. J., Taxonomy and plant conservation, Cambridge University Press, 2006, 174 191. 173. Mues R., Preceedings of the phytochemical society of Europe 29, Bryophytes Their Chemistry and Chemistry Taxonomy, Clarendon Press, 1990,421. 174. Asakawa, Y., Lin X. H., Kondo Keiko, and Fukuyama, Y., Phytochemistry, 1991, 30, 4019. 175. Asakawa, Y, Phytochemistry, 2001, 56, 297. 176. Verpoorte, R., Bioassay Methods in Natural Product Research and Drug Development, Kluwer Academic Publishers, 1999, 11. 175 [...]... Selective NOE effects of 164 Figure 3-6, Selective HMBC correlations of 176 Figure 3-7, Selective HMBC correlations of 191 Figure 3-8, Selective NOE effects of 191 Figure 3-9, Selective HMBC correlations of 198 Figure 3-10, Selective HMBC correlations of 200 Figure 3-11, Selective NOE effects of 200 Figure 3-12, ORTEP drawing of pyridinium part of 227 Figure 3-13, ORTEP drawing of 229 xi List of Schemes Scheme... of 229 xi List of Schemes Scheme 2-1, Proposed biogenesis of 94 Scheme 2-2, Proposed biogenesis of 107 Scheme 2-3, Proposed biogenesis of 109-112 Scheme 2-4, Phenolic compounds from moss species Scheme 3-1, Proposed biogenesis of 191 Scheme 3-2, Formation of the p-bromobenzenesulphate salt 227 Scheme 3-3, Methanolysis of 231 to 230 xii List of abbreviations CC: Column Chromatography COSY: Correlation... major component of peel oil from oranges and lemons, has a production of 50,000 tons annually at the low cost of US$ 1-2/kg Meanwhile, the closely related monoterpenoid perillyl alcohol (38) is widely used in perfume industries and commands much higher prices of more than US$ 30/kg Obviously the conversion of limonene to give perillyl alcohol would be a profitable business Each enantiomer of these monoterpenoids... 5',3'''-dihydroxyamentoflavone (40), Bartramia pomiformis (Bartramiaceae) [57] 5',3'''-dihydroxyamentoflavone (40), philonotisoflavone (53), 2,3-dihydrophilonotisoflavone (55), anhydrobartramiaflavone (69), bartramiaflavone (70), Philonotis fontana (Bartramiaceae) [58] 5',3'''-dihydroxyamentoflavone (40), 5',3'''-dihydroxyrobustaflavone (45) dicranolomin (48), 2,3-dihydro-5',3'''-hydroxyamentoflavone (47), philonotisoflavone... shorten the production time of secondary metabolites However, most of these methods focus on microorganisms because large quantities are available from simple fermentation and the complete genome sequences of a number of species have also been determined OSMAC (One Strain – Many Compounds) is another technique for the study of microbe secondary metabolites The genome sequences of microorganisms show that... India and many other developing countries It was only natural that the beginning of organic chemistry involved studies of biologically active compounds that were readily available from natural sources Efforts in this field have led to the isolation of many compounds, some of which have been widely used as drugs to save millions of lives These compounds include anti-malarial agents like quinine (8), artemisinin... earth [38] Bryophytes share some common characteristics: (1) all have a gametophyte-dominant life cycle; (2) the gametophyte consists of simple leaf and stemlike or thalloid food production organs anchored to the soil by rhizoids; (3) the sporophyte is attached to the gametophyte and is usually completely dependent on it for nourishment [39] Until now, the chemistry of less than 10% of bryophytes has... 5'-hydroxyamentoflavone (39), 5',3'''-dihydroxyamentoflavone (40), 5'-hydroxyrobustaflavone (44), 2,3-dihydro-5'-hydroxy-amentoflavone (46) Campylopus clavatus (Dicranaceae) [52] 5',3'''-dihydroxyamentoflavone (40), 5',3'''-dihydroxyrobustaflavone (45), campylopusaurone (71) 5',3'''-dihydroxyamentoflavone (40), 5',3'''-dihydroxyrobustaflavone (45), campylopusaurone (71) Campylopus introflexus (Dicranaceae)... Less than 1% of bacterial and 5% of fungi species are believed to be known to Science Only a few of these have been studied due to difficulties with their cultivation properties [24] The number of microorganism is estimated to be in the range of 105 to 106 This large number requires scientists to find a practicable strategy to select the species to study Endophytic microorganisms are one of the best... 1.4.2 Natural products from liverworts The chemistry of many liverwort species has been extensively studied and a variety of secondary metabolites have been isolated Terpenoids are considered to be the characteristic metabolites of liverworts However, bibenzyls and their di- and tetramers are also frequently produced Terpenoids are a group of compounds built up of simple or multiple C5 units Dimethylallyl . compounds. Chapter Four briefly discusses the use of the chemistry of bryophytes in taxonomy. The results showed that the chemistry of bryophytes could provide taxonomic supporting information. DEPARTMENT OF CHEMISTRY NATIONAL UNIVERSITY OF SINGAPORE 2007 ii ACKNOWLEDGEMENTS First of all, I would like to gratefully acknowledge the enthusiastic supervision of Professor Leslie. CHEMISTRY OF BRYOPHYTES GE XIAOWEI (M.Sc., CHINESE ACADEMY OF PREVENTIVE MEDICINE) A THESIS SUBMITED FOR THE DEGREE OF DOCTOR OF