Skip to main content
Book cover

Natural Products pp 197–227Cite as

Terpenoids As Therapeutic Drugs and Pharmaceutical Agents

  • Chapter

Abstract

Terpenoids, also referred to as terpenes, are the largest group of natural compounds. Many terpenes have biological activities and are used for the treatment of human diseases. The worldwide sales of terpene-based pharmaceuticals in 2002 were approximately US $12 billion. Among these pharmaceuticals, the anticancer drug Taxol® and the antimalarial drug Artimesinin are two of the most renowned terpene-based drugs. All terpenoids are synthesized from two five-carbon building blocks. Based on the number of the building blocks, terpenoids are commonly classified as monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and sesterterpenes (C25). These terpenoids display a wide range of biological activities against cancer, malaria, inflammation, and a variety of infectious diseases (viral and bacterial). In last two decades, natural-product bioprospecting from the marine environment has resulted in hundreds of terpenoids with novel structures and interesting bioactivities, with more to be discovered in the future. The problem of supply is a serious obstacle to the development of most terpenoid compounds with interesting pharmaceutical properties. Although total chemical synthesis plays a less important role in the production of some terpenoid drugs, it has contributed significantly to the development of terpenoid compounds and terpene-based drugs by providing critical information on structure-activity relationships (SAR) and chiral centers as well as generating analog libraries. Semisynthesis, on the other hand, has played a major role in the development and production of terpenoid-derived drugs. Metabolic engineering as an integrated bioengineering approach has made considerable progress to produce some terpenoids in plants and fermentable hosts. Cell culture and aquaculture will provide a solution for the supply issue of some valuable terpenes from terrestrial and marine environments, respectively. Recent advances in environmental genomics and other “-omics” technologies will facilitate isolation and discovery of new terpenoids from natural environments. There is no doubt that more terpenoid-based clinical drugs will become available and will play a more significant role in human disease treatment in the near future.

Key Words

  • Natural products
  • bioactive terpenoids
  • biosynthesis
  • chemical synthesis
  • drug discovery and development
  • sustainable production

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-59259-976-9_9
  • Chapter length: 31 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   189.00
Price excludes VAT (USA)
  • ISBN: 978-1-59259-976-9
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   249.99
Price excludes VAT (USA)
Hardcover Book
USD   249.99
Price excludes VAT (USA)
Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Newman DJ, Cragg GM, Snader KM. The influence of natural products upon drug discovery. Nat Prod Rep 2000;17(3):215–234.

    PubMed  CAS  Google Scholar 

  2. Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 2003;66(7):1022–1037.

    PubMed  CAS  Google Scholar 

  3. Hill RA. Terpenoids. In: Thomson RH (ed), The Chemistry of Natural Products. Chapman & Hall, Blackie Academic & Professional, New York:;, 1993.

    Google Scholar 

  4. Eisenreich W, Schwarz M, Cartayrade A, Arigoni D, Zenk MH, Bacher A. The deoxyxylulose phosphate pathway of terpenoid biosynthesis in plants and microorganisms. Chem Biol 1998;5(9):R221–R233.

    PubMed  CAS  Google Scholar 

  5. Lindel T, Jensen PR, Fenical W, et al. Eleutherobin, a new cytotoxin that mimics paclitaxel (taxol) by stabilizing microtubules. J Am Chem Soc 1997;119(37):8744–8745.

    CAS  Google Scholar 

  6. D’Ambrosio M, Guerriero A, Pietra F. Sarcodictyin a and sarcodictyin b novel diterpenoidic alcohols esterified by e-n1 methylurocanic acid isolation from the mediterranean stolonifer sarcodictyon-roseum. Helv Chim Acta 1987;70(8):2019–2027.

    CAS  Google Scholar 

  7. D’Ambrosio M, Guerriero A, Pietra F. Isolation from the mediterranean stoloniferan coral sarcodictyon-roseum of sarcodictyin c d e and f novel diterpenoidic alcohols esterified by e or z-n1 methylurocanic acid failure of the carbon-skeleton type as a classification criterion. Helv Chim Acta 1988;71(5):964–976.

    CAS  Google Scholar 

  8. Dubey VS, Bhalla R, Luthra R. An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants. J Biosci 2003;28(5):637–646.

    PubMed  CAS  Google Scholar 

  9. Kuzuyama T, Seto H. Diversity of the biosynthesis of the isoprene units. Nat Prod Rep 2003;20(2):171–183.

    PubMed  CAS  Google Scholar 

  10. Buchanan SG. Structural genomics: bridging functional genomics and structure-based drug design. Curr Opin Drug Discov Dev 2002;5(3):367–381.

    CAS  Google Scholar 

  11. Kuzuyama T. Mevalonate and nonmevalonate pathways for the biosynthesis of isoprene units. Biosci Biotechnol Biochem 2002;66(8):1619–1627.

    PubMed  CAS  Google Scholar 

  12. Dewick PM. The biosynthesis of C-5-C-25 terpenoid compounds. Nat Prod Rep 2002;19(2): 181–222.

    PubMed  CAS  Google Scholar 

  13. Dewick PM. The mevalonate and deoxyxylulose phosphate pathways: terpenoids and steroids. In: Dewick PM (ed), Medicinal Natural Products. John Wiley & Sons, Ltd., 2002.

    Google Scholar 

  14. Rohdich F, Kis K, Bacher A, Eisenreich W. The non-mevalonate pathway of isoprenoids: genes, enzymes and intermediates. Curr Opin Chem Biol 2001;5(5):535–540.

    PubMed  CAS  Google Scholar 

  15. Wanke M, Skorupinska-Tudek K, Swiezewska E. Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway. Acta Biochim Pol 2001;48(3):663–672.

    PubMed  CAS  Google Scholar 

  16. Moore BS. Biosynthesis of marine natural products: microorganisms and macroalgae. Nat Prod Rep 1999;16(6):653–674.

    PubMed  CAS  Google Scholar 

  17. Lichtenthaler HK. The 1-deoxy-D-xylulose-5-phosphate pathway of isoprenoid biosynthesis in plants. Annu Rev Plant Physiol Plant Molec Biol 1999;50:47–65.

    CAS  Google Scholar 

  18. Ogura K, Koyama T. Enzymatic aspects of isoprenoid chain elongation. Chem Rev 1998; 98(N4):1263–1276.

    PubMed  CAS  Google Scholar 

  19. Wang KC, Ohnuma S-i. Isoprenyl diphosphate synthases. Biochim Biophys Acta 2000;1529(1-3):33–48.

    PubMed  CAS  Google Scholar 

  20. Poulter CD, and Rilling, H. C. In: Spurgeon SL, and Port JW (eds), Biosynthesis of Isoprenoid Compounds. John Wiley & Sons, New York: 1981; pp. 161–224.

    Google Scholar 

  21. Heide L, Berger U. Partial purification and properties of geranyl pyrophosphate synthase from Lithospermum erythrorhizon cell cultures. Arch Biochem Biophys 1989;273(2):331–338.

    PubMed  CAS  Google Scholar 

  22. Ohnuma S-I, Hirooka K, Tsuruoka N, et al. A pathway where polyprenyl diphosphate elongates in prenyltransferase: Insight into a common mechanism of chain length determination of prenyltransferases. J Biol Chem 1998;273(41):26,705–26,713.

    PubMed  CAS  Google Scholar 

  23. Tachibana A, Yano Y, Otani S, Nomura N, Sako Y, Taniguchi M. Novel prenyltransferase gene encoding farnesylgeranyl diphosphate synthase from a hyperthermophilic archaeon Aeropyrum pernix—molecular evolution with alteration in product specificity. Eur J Biochem 2000;267(2): 321–328.

    PubMed  CAS  Google Scholar 

  24. Tachibana A. A novel prenyltransferase, farnesylgeranyl diphosphate synthase, from the haloalkaliphilic archaeon, Natronobacterium-pharaonis. FEBS Lett 1994;341(2-3):291–294.

    PubMed  CAS  Google Scholar 

  25. Caruthers JM, Kang I, Rynkiewicz MJ, Cane DE, Christianson DW. Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti. J Biol Chem 2000;275(33):25,533–25,539.

    PubMed  CAS  Google Scholar 

  26. Lesburg CA, Zhai GZ, Cane DE, Christianson DW. Crystal structure of pentalenene synthase— mechanistic insights on terpenoid cyclization reactions in biology. Science 1997;277(5333): 1820–1824.

    PubMed  CAS  Google Scholar 

  27. Lesburg CA, Caruthers JM, Paschall CM, Christianson DW. Managing and manipulating carbocations in biology: terpenoid cyclase structure and mechanism. Curr Opin Struct Biol 1998;8(6):695–703.

    PubMed  CAS  Google Scholar 

  28. Abe I RM, Prestwich G. D. Enzymatic cyclization of squalene and squalene oxide to sterols and triterpenes. Chem Rev 1993;93:2189–2206.

    CAS  Google Scholar 

  29. Cane DE. Enzymatic formation of sesquiterpenes. Chem Rev 1990;90:1089–1103.

    CAS  Google Scholar 

  30. Rising KA, Starks CM, Noel JP, Chappell J. Demonstration of germacrene A as an intermediate in 5-epi-aristolochene synthase catalysis. J Am Chem Soc 2000;122(9):1861–1866.

    CAS  Google Scholar 

  31. Rohmer M. The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants. Nat Prod Rep 1999;16(5):565–574.

    PubMed  CAS  Google Scholar 

  32. Wagner KH, Elmadfa I. Biological relevance of terpenoids—overview focusing on mono-, diand tetraterpenes. Ann Nutr Metab 2003;47(3–4):95–106.

    PubMed  CAS  Google Scholar 

  33. Kuroda C, Suzuki H. Synthesis of odd-membered rings by the reaction of beta-carbonylallylsilane or its derivative as a carbon 1,3-dipole. Curr Org Chem 2003;7(2):115–131.

    CAS  Google Scholar 

  34. Ridley RG. Medical need, scientific opportunity and the drive for antimalarial drugs. Nature 2002;415(6872):686–693.

    PubMed  CAS  Google Scholar 

  35. Abdin MZ, Israr M, Rehman RU, Jain SK. Artemisinin, a novel antimalarial drug: Biochemical and molecular approaches for enhanced production. Planta Med 2003;69(4):289–299.

    PubMed  CAS  Google Scholar 

  36. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther 2002;27(6):391–401.

    PubMed  CAS  Google Scholar 

  37. Altaha R, Fojo T, Reed E, Abraham J. Epothilones: a novel class of non-taxane microtubulestabilizing agents. Curr Pharm Design 2002;8(19):1707–1712.

    CAS  Google Scholar 

  38. Altmann KH. Microtubule-stabilizing agents: a growing class of important anticancer drugs. Curr Opin Chem Biol 2001;5(4):424–431.

    PubMed  CAS  Google Scholar 

  39. Bez G, Kalita B, Sarmah P, Barua NC, Dutta DK. Recent developments with 1,2,4-trioxanetype artemisinin analogues. Curr Org Chem 2003;7(12):1231–1255.

    CAS  Google Scholar 

  40. Blunt JW, Copp BR, Munro MHG, Northcote PT, Prinsep MR. Marine natural products. Nat Prod Rep 2003;20(1):1–48.

    PubMed  CAS  Google Scholar 

  41. Bongiorni L, Pietra F. Marine natural products for industrial applications. Chem Indus 1996(2):54–58.

    Google Scholar 

  42. Borzilleri RM, Vite GD. Epothilones: new tubulin polymerization agents in preclinical and clinical development. Drug Future 2002;27(12):1149–1163.

    CAS  Google Scholar 

  43. Burkhart CG, Burkhart CN, Burkhart KM. An assessment of topical and oral prescription and over-the-counter treatments for head lice. J Am Acad Derm 1998;38(6 Part 1):979–982.

    PubMed  CAS  Google Scholar 

  44. Caniato R, Puricelli L. Review: natural antimalarial agents (1995–2001). Crit Rev Plant Sci 2003;22(1):79–105.

    CAS  Google Scholar 

  45. Cantrell CL, Franzblau SG, Fischer NH. Antimycobacterial plant terpenoids. Planta Med 2001;67(8):685–694.

    PubMed  CAS  Google Scholar 

  46. Carte BK. Biomedical potential of marine natural products. Bioscience 1996;46(4):271–86.

    Google Scholar 

  47. Chakraborty Tushar K, Das S. Chemistry of potent anti-cancer compounds, amphidinolides. Curr Med Chem Anticancer Agents 2001;1(2):131–149.

    Google Scholar 

  48. De Clercq E. Current lead natural products for the chemotherapy of human immunodefiency virus (HIV) infection. Med Res Rev 2000;20(5):323–349.

    PubMed  Google Scholar 

  49. Donia M, Hamann MT. Marine natural products and their potential applications as anti-infective agents. Lancet Infect Dis 2003;3(6):338–348.

    PubMed  CAS  Google Scholar 

  50. El Sayed KA, Bartyzel P, Shen XY, Perry TL, Kjawiony JK, Hamann MT. Marine natural products as antituberculosis agents. Tetrahedron 2000;56(7):949–953.

    Google Scholar 

  51. Frederich M, Dogne JM, Angenot L, De Mol P. New trends in anti-malarial agents. Curr Med Chem 2002;9(15):1435–1456.

    PubMed  CAS  Google Scholar 

  52. Fujiki H, Suganuma M, Yatsunami J, et al. Significant marine natural products in cancer research. Gaz Chim Ital 1993;123(6):309–316.

    CAS  Google Scholar 

  53. Gochfeld DJ, El Sayed KA, Yousaf M, et al. Marine natural products as lead anti-HIV agents. Minni Rev Med Chem 2003;3(5):401–424.

    CAS  Google Scholar 

  54. Gogas H, Fountzilas G. The role of taxanes as a component of neoadjuvant chemotherapy for breast cancer. Ann Oncol 2003;14(5):667–674.

    PubMed  CAS  Google Scholar 

  55. Haefner B. Drugs from the deep: marine natural products as drug candidates. Drug Discov Today 2003;8(12):536–544.

    PubMed  CAS  Google Scholar 

  56. Haynes RK. Artemisinin and derivatives: the future for malaria treatment? Curr Opin Infect Dis 2001;14(6):719–726.

    PubMed  CAS  Google Scholar 

  57. Heras BDL, Rodriguez B, Bosca L, Villar AM. Terpenoids: sources, structure elucidation and therapeutic potential in inflammation. Curr Topics Med Chem 2003;3:171–185.

    Google Scholar 

  58. Heym B, Cole ST. Multidrug resistance in Mycobacterium tuberculosis. Int J Antimicrob Agents 1997;8(1):61–70.

    CAS  PubMed  Google Scholar 

  59. Ireland Chris M. Mining the world’s oceans for medicinals. Cancer Epidem Biomark Prevention 2002;11(10 Part 2).

    Google Scholar 

  60. Itokawa H, Takeya K, Hitotsuyanagi Y, Morita H. Antitumor compounds isolated from higher plants. Yakugaku Zasshi 1999;119(8):529–583.

    PubMed  CAS  Google Scholar 

  61. Jefford CW. Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action. Curr Med Chem 2001;8(15):1803–1826.

    PubMed  CAS  Google Scholar 

  62. Jung M, Lee S, Kim H, Kim H. Recent studies on natural products as anti-HIV agents. Curr Med Chem 2000;7(6):649–661.

    PubMed  CAS  Google Scholar 

  63. Kavallaris M, Verrills NM, Hill BT. Anticancer therapy with novel tubulin-interacting drugs. Drug Resist Update 2001;4(6):392–401.

    CAS  Google Scholar 

  64. Koenig Gabriele M, Wright Anthony D, Franzblau Scott G. Assessment of antimycobacterial activity of a series of mainly marine derived natural products. Planta Med 2000;66(4):337–342.

    Google Scholar 

  65. Kris-Etherton PM, Hecker KD, Bonanome A, et al. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med 2002;113(Suppl 9B):71–88.

    Google Scholar 

  66. Lloyd AW. Marine natural products as therapeutic agents. Drug Discov Today 2000;5(1):34.

    Google Scholar 

  67. Mann J. Natural products in cancer chemotherapy: past, present and future. Nat Revs Cancer 2002;2(2):143–148.

    CAS  Google Scholar 

  68. Mayer Alejandro MS, Gustafson Kirk R. Marine pharmacology in 2000: Antitumor and cytotoxic compounds. Int J Cancer 2003;105(3):291–299.

    PubMed  CAS  Google Scholar 

  69. Mayer Alejandro MS, Lehmann Virginia KB. Marine pharmacology in 1999: antitumor and cytotoxic compounds. Anticancer Res 2001;21(4A):2489–2500.

    Google Scholar 

  70. Proksch P, Edrada RA, Ebel R. Drugs from the seas—current status and microbiological implications. Appl Microbiol Biotechnol 2002;59(2-3):125–134.

    PubMed  CAS  Google Scholar 

  71. Wylie Bryan L, Ernst Nadia B, Grace Krista JS, Jacobs Robert S. Marine natural products as phospholipase A-2 inhibitors. Progress in Surgery Uhl, W 1997;24:146–152.

    Google Scholar 

  72. Loza-Tavera H. Monoterpenes in essential oils-biosynthesis and properties. Adv Exp Med Biol 1999;464:49–62.

    PubMed  CAS  Google Scholar 

  73. Little DB, Croteau R. Biochemistry of essential oil plants: a thirty year overview. In: Teranishi R, Wick EL, Hornstein I (eds), Flavor Chemistry: Thirty years of Progress: Kluwer Academic/ Plenum, 1999.

    Google Scholar 

  74. Niinemets U, Hauff K, Bertin N, Tenhunen JD, Steinbrecher R, Seufert G. Monoterpene emissions in relation to foliar photosynthetic and structural variables in Mediterranean evergreen Quercus species. New Phytol 2002;153(2):243–256.

    CAS  Google Scholar 

  75. Sharkey TD, Yeh SS. Isoprene emission from plants. Annu Rev Plant Physiol Plant Molec Biol 2001;52:407–436.

    CAS  Google Scholar 

  76. Davis EM, Croteau R. Cyclization enzymes in the biosynthesis of monoterpenes, sesquiterpenes, and diterpenes. Biosynth Arom Polyket Isopren Alkal 2000;209:53–95.

    CAS  Google Scholar 

  77. Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr 1999;129(3): 775S–778S.

    PubMed  CAS  Google Scholar 

  78. Duetz WA, Fjallman AHM, Ren SY, Jourdat C, Witholt B. Biotransformation of D-limonene to (+) trans-carveol by toluene-grown Rhodococcus opacus PWD4 cells. Appl Environ Microbiol 2001;67(6):2829–2832.

    PubMed  CAS  Google Scholar 

  79. Fabian CJ. Breast cancer chemoprevention: beyond tamoxifen. Breast Cancer Res 2001;3(2): 99–103.

    PubMed  CAS  Google Scholar 

  80. Wattenberg LW, Sparnins VL, Barany G. Inhibition of N nitrosodiethylamine carcinogenesis in mice by naturally occurring organosulfur compounds and monoterpenes. Cancer Res 1989;49(10):2689–2692.

    PubMed  CAS  Google Scholar 

  81. Crowell PL, Kennan WS, Vedejs E, Gould MN. Chemoprevention of mammary carcinogenesis by hydroxylated metabolites of limonene. In: 81st Annual Meeting of the American Association for Cancer Research, Washington, DC, USA, May 23–26, 1990. Proc Am Assoc Cancer Res Annu Meet 1990.

    Google Scholar 

  82. Mills JJ, Chari RS, Boyer IJ, Gould MN, Jirtle RL. Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol. Cancer Res 1995;55(5):979–983.

    PubMed  CAS  Google Scholar 

  83. Haag JD, Gould MN. Mammary carcinoma regression induced by perillyl alcohol, a hydroxylated analog of limonene. Cancer Chem Pharm 1994;34(6):477–483.

    CAS  Google Scholar 

  84. Stark MJ, Burke YD, McKinzie JH, Ayoubi AS, Crowell PL. Chemotherapy of pancreatic cancer with the monoterpene perillyl alcohol. Cancer Lett 1995;96(1):15–21.

    PubMed  CAS  Google Scholar 

  85. McNamee D. Limonene trial in cancer. Lancet 1993;342(8874):801.

    Google Scholar 

  86. Phillips LR, Malspeis L, Supko JG. Pharmacokinetics of active drug metabolites after oral administration of perillyl alcohol, an investigational antineoplastic agent, to the dog. Drug Metab Disposi 1995;23(7):676–680.

    CAS  Google Scholar 

  87. Liu G, Oettel K, Bailey H, et al. Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer. Invest New Drugs 2003;21(3):367–372.

    PubMed  CAS  Google Scholar 

  88. Ariazi EA, Satomi Y, Ellis MJ, et al. Activation of the transforming growth factor beta signaling pathway and induction of cytostasis and apoptosis in mammary carcinomas treated with the anticancer agent perillyl alcohol. Cancer Res 1999;59(8):1917–1928.

    PubMed  CAS  Google Scholar 

  89. Crowell PL, Chang RR, Ren Z, Elson CE, Gould MN. Selective inhibition of isoprenylation of 21-26-Kda proteins by the anticarcinogen D-limonene and its metabolites. J Biol Chem 1991;266(26):17,679–17,685.

    PubMed  CAS  Google Scholar 

  90. Hitmi A, Coudret A, Barthomeuf C. The production of pyrethrins by plant cell and tissue cultures of Chrysanthemum cinerariaefolium and Tagetes species. Crit Rev Biochem Mol Biol 2000;35(5):317–337.

    PubMed  CAS  Google Scholar 

  91. George J, Bais HP, Ravishankar GA. Biotechnological production of plant-based insecticides. Crit Rev Biotechnol 2000;20(1):49–77.

    PubMed  CAS  Google Scholar 

  92. Jones KN, English JC. Review of common therapeutic options in the United States for the treatment of Pediculosis capitis. Clin Infect Dis 2003;36(11):1355–1361.

    PubMed  CAS  Google Scholar 

  93. Pollack RJ, Kiszewski A, Armstrong P, et al. Differential permethrin susceptibility of head lice sampled in the United States and Borneo. Arch Pediatr Adolesc Med 1999;153(9):969–73.

    PubMed  CAS  Google Scholar 

  94. Fuller RW, Cardellina JH, Jurek J, et al. Isolation and structure activity features of halomonrelated antitumor monoterpenes from the red alga Portieria hornemannii. J Med Chem 1994;37(25):4407–4411.

    PubMed  CAS  Google Scholar 

  95. Egorin MJ, Rosen DM, Benjamin SE, Callery PS, Sentz DL, Eiseman JL. In vitro metabolism by mouse and human liver preparations of halomon, an antitumor halogenated monoterpene. Cancer Chem Pharm 1997;41(1):9–14.

    CAS  Google Scholar 

  96. Sotokawa T, Noda T, Pi S, Hirama M. A three-step synthesis of halomon. Angew Chem 2000;39(19):3430–3432.

    CAS  Google Scholar 

  97. Rajab MS, Cantrell CL, Franzblau SG, Fischer NH. Antimycobacterial activity of (e)-phytol and derivatives—a preliminary structure-activity study. Planta Med 1998;64(1):2–4.

    PubMed  CAS  Google Scholar 

  98. Abraham WR. Bioactive sesquiterpenes produced by fungi: are they useful for humans as well? Curr Med Chem 2001;8(6):583–606.

    PubMed  CAS  Google Scholar 

  99. Asakawa Y, Toyota M, Nagashima F, Hashimoto T, El Hassane L. Sesquiterpene lactones and acetogenin lactones from the Hepaticae and chemosystematics of the liverworts Frullania, Plagiochila and Porella. Heterocycles 2001;54(2):1057∓.

    CAS  Google Scholar 

  100. Tayler VE. The honest herbal—a sensible guide to the use of herbs and related remedies. Third ed. New York: The Haworth Press, 1993.

    Google Scholar 

  101. Smolinski AT, Pestka JJ. Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb-1 (ginseng) and parthenolide (feverfew). Food Chem Toxicol 2003;41(10): 1381–1390.

    PubMed  CAS  Google Scholar 

  102. Schinella GR, Giner RM, Recio MD, De Buschiazzo PM, Rios JL, Manez S. Anti-inflammatory effects of South American Tanacetum vulgare. J Pharm Pharmacol 1998;50(9):1069–1074.

    PubMed  CAS  Google Scholar 

  103. Jain NK, Kulkarni SK. Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats. J Ethnopharmacol 1999;68(1-3):251–259.

    PubMed  CAS  Google Scholar 

  104. Williams CA, Harborne JB, Geiger H, Robin J, Hoult S. The flavonoids of Tanacetum parthenium and T. vulgare and their anti-inflammatory properties. Phytochemistry 1999;51(3): 417–423.

    PubMed  CAS  Google Scholar 

  105. Sheehan M, Wong HR, Hake PW, Zingarelli B. Parthenolide improves systemic hemodynamics and decreases tissue leukosequestration in rats with polymicrobial sepsis. Crit Care Med 2003;31(9):2263–2270.

    PubMed  CAS  Google Scholar 

  106. Brossi A, Venugopalan B, Gerpe LD, et al. Arteether, a new antimalarial drug: synthesis and antimalarial properties. J Med Chem 1988;31(3):645–650.

    PubMed  CAS  Google Scholar 

  107. Robert A, Dechy-Cabaret O, Cazelles J, Meunier B. From mechanistic studies on artemisinin derivatives to new modular antimalarial drugs. Accounts Chem Res 2002;35(3):167–174.

    CAS  Google Scholar 

  108. Delabays N, Simonnet X, Gaudin M. The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars. Curr Med Chem 2001;8(15):1795–1801.

    PubMed  CAS  Google Scholar 

  109. Safayhi H, Sabieraj J, Sailer ER, Ammon HPT. Chamazulene—an antioxidant-type inhibitor of leukotriene B-4 formation. Planta Med 1994;60(5):410–413.

    PubMed  CAS  Google Scholar 

  110. Konig GM, Wright AD, Franzblau SG. Assessment of antimycobacterial activity of a series of mainly marine derived natural products. Planta Med 2000;66(4):337–342.

    PubMed  CAS  Google Scholar 

  111. Hamann MT, Scheuer PJ, Kellyborges M. Biogenetically diverse, bioactive constituents of a sponge, order verongida—bromotyramines and sesquiterpene-shikimate derived metabolites. J Org Chem 1993;58(24):6565–6569.

    CAS  Google Scholar 

  112. Nasu SS, Yeung BKS, Hamann MT, Scheuer PJ, Kellyborges M, Goins K. Puupehenone-related metabolites from two hawaiian sponges Hyrtios spp. J Org Chem 1995;60(22):7290–7292.

    CAS  Google Scholar 

  113. Zjawiony JK, Bartyzel P, Hamann MT. Chemistry of puupehenone: 1,6-conjugate addition to its quinone-methide system. J Nat Prod 1998;61(12):1502–1508.

    PubMed  CAS  Google Scholar 

  114. Capon RJ. Marine sesquiterpene/quinone. In: Atta-ur-Rahaman (ed), Studies in Natural Products. Elsevier, New York: 1995; pp. 289–326.

    Google Scholar 

  115. Rodriguez J, Quinoa E, Riguera R, Peters BM, Abrell LM, Crews P. The structures and stereochemistry of cytotoxic sesquiterpene quinones from Dactylospongia elegans. Tetrahedron 1992;48(32):6667–6680.

    CAS  Google Scholar 

  116. Alvi KA, Diaz Maria C, Crews P, Slate DL, Lee RH, Moretti R. Evaluation of new sesquiterpene quinones from two Dysidea sponge species as inhibitors of protein tyrosine kinase. J Org Chem 1992;57(24):6604–6607.

    CAS  Google Scholar 

  117. Deguzman FS, Copp BR, Mayne CL, et al. Bolinaquinone—a novel cytotoxic sesquiterpene hydroxyquinone from a Philippine Dysidea sponge. J Org Chem 1998;63(22):8042–8044.

    CAS  Google Scholar 

  118. Giannini C, Debitus C, Posadas I, Paya M, D’Auria MV. Dysidotronic acid, a new and selective human phospholipase A(2) inhibitor from the sponge Dysidea sp. Tetrahedron Lett 2000;41(17):3257–3260.

    CAS  Google Scholar 

  119. Giannini C, Debitus C, Lucas R, et al. New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A(2) and other leukocyte functions. J Nat Prod 2001;64(5):612–615.

    PubMed  CAS  Google Scholar 

  120. Lucas R, Giannini C, D’Auria MV, Paya M. Modulatory effect of bolinaquinone, a marine sesquiterpenoid, on acute and chronic inflammatory processes. J Pharmacol Exp Ther 2003;304(3):1172–1180.

    PubMed  CAS  Google Scholar 

  121. Loya S, Hizi A. The inhibition of human immunodeficiency virus type-1 reverse transcriptase by avarol and avarone derivatives. FEBS Lett 1990;269(1):131–134.

    PubMed  CAS  Google Scholar 

  122. Ling TT, Xiang AX, Theodorakis EA. Enantioselective total synthesis of avarol and avarone. Angew Chem 1999;38(20):3089–3091.

    CAS  Google Scholar 

  123. Loya S, Tal R, Kashman Y, Hizi A. Illimaquinone a selective inhibitor of the RNAase H activity of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemotherapy 1990;34(10):2009–2012.

    CAS  Google Scholar 

  124. Ling T, Poupon E, Rueden EJ, Theodorakis EA. Synthesis of (-)-ilimaquinone via a radical decarboxylation and quinone addition reaction. Org Lett 2002;4(5):819–822.

    PubMed  CAS  Google Scholar 

  125. McMorris TC, Yu J, Lira R, et al. Structure-activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues. J Org Chem 2001;66(18):6158–6163.

    PubMed  CAS  Google Scholar 

  126. McMorris TC, Kashinatham A, Lira R, et al. Sesquiterpenes from Omphalotus illudens. Phytochemistry 2002;61(4):395–398.

    PubMed  CAS  Google Scholar 

  127. McMorris TC, Lira R, Gantzel PK, Kelner MJ, Dawe R. Sesquiterpenes from the basidiomycete Omphalotus illudens. J Nat Prod 2000;63(11):1557–1559.

    PubMed  CAS  Google Scholar 

  128. Kelner MJ, McMorris TC, Montoya MA, et al. Characterization of cellular accumulation and toxicity of illudin S in sensitive and nonsensitive tumor cells. Cancer Chem Pharm 1997;40(1):65–71.

    CAS  Google Scholar 

  129. Herzig MCS, Arnett B, MacDonald JR, Woynarowski JM. Drug uptake and cellular targets of hydroxymethylacylfulvene (HMAF). Biochem Pharmcol 1999;58(2):217–225.

    CAS  Google Scholar 

  130. Woynarowski JM, Napier C, Koester SK, et al. Effects on dna integrity and apoptosis induction by a novel antitumor sesquiterpene drug, 6-hydroxymethylacylfulvene (hmaf, mgi 114). Biochem Pharmcol 1997;54(11):1181–1193.

    CAS  Google Scholar 

  131. Izbicka E, Davidson K, Lawrence R, Cote R, MacDonald JR, Von Hoff DD. Cytotoxic effects of MGI 114 are independent of tumor p53 or p21 expression. Anticancer Res 1999;19(2A): 1299–1307.

    PubMed  CAS  Google Scholar 

  132. Woynarowska BA, Woynarowski JM, Herzig MCS, Roberts K, Higdon AL, MacDonald JR. Differential cytotoxicity and induction of apoptosis in tumor and normal cells by hydroxymethylacylfulvene (HMAF). Biochem Pharmcol 2000;59(10):1217–1226.

    CAS  Google Scholar 

  133. Jaspers NGJ, Raams A, Kelner MJ, et al. Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription-and replication-coupled repair pathways. DNA Repair 2002;1(12):1027–1038.

    PubMed  CAS  Google Scholar 

  134. Hanson JR. Diterpenoids. Nat Prod Rep 2003;20(1):70–78.

    PubMed  CAS  Google Scholar 

  135. Sung PJ, Chen MC. The heterocyclic natural products of gorgonian corals of genus Briareum exclusive of briarane-type diterpenoids. Heterocycles 2002;57(9):1705–1715.

    CAS  Google Scholar 

  136. Bruno M, Piozzi F, Rosselli S. Natural and hemisynthetic neoclerodane diterpenoids from Scutellaria and their antifeedant activity. Nat Prod Rep 2002;19(3):357–378.

    PubMed  CAS  Google Scholar 

  137. Hanson JR. Diterpenoids. Nat Prod Rep 2002;19(2):125–132.

    PubMed  CAS  Google Scholar 

  138. Sung PJ, Sheu JH, Xu JP. Survey of briarane-type diterpenoids of marine origin. Heterocycles 2002;57(3):535–579.

    CrossRef  CAS  Google Scholar 

  139. Hanson JR. Diterpenoids. Nat Prod Rep 2001;18(1):88–94.

    PubMed  CAS  Google Scholar 

  140. Hanson JR. Diterpenoids. Nat Prod Rep 2000;17(2):165–174.

    PubMed  CAS  Google Scholar 

  141. Baloglu E, Kingston DGI. The taxane diterpenoids. J Nat Prod 1999;62(10):1448–1472.

    PubMed  CAS  Google Scholar 

  142. Hanson JR. Diterpenoids. Nat Prod Rep 1999;16(2):209–219.

    CAS  Google Scholar 

  143. Hanson JR. Diterpenoids. Nat Prod Rep 1998;15(1):93–106.

    CAS  Google Scholar 

  144. Hanson JR. Diterpenoids. Nat Prod Rep 1997;14(3):245–258.

    CAS  Google Scholar 

  145. Hanson JR. Diterpenoids. Nat Prod Rep 1996;13(1):59–71.

    PubMed  CAS  Google Scholar 

  146. Hanson JR. Diterpenoids. Nat Prod Rep 1995;12(2):207–218.

    CAS  Google Scholar 

  147. Rontani JF, Volkman JK. Phytol degradation products as biogeochemical tracers in aquatic environments. Org Geochem 2003;34(1):1–35.

    CAS  Google Scholar 

  148. Broker LE, Glaccone G. The role of new agents in the treatment of non-small cell lung cancer. Eur J Cancer 2002;38(18):2347–2361.

    PubMed  CAS  Google Scholar 

  149. Myles DC. Emerging microtubule stabilizing agents for cancer chemotherapy. Ann Rep Med Chem 2002;37(37):125–132.

    CrossRef  CAS  Google Scholar 

  150. Mollinedo F, Gajate C. Microtubules, microtubule-interfering agents and apoptosis. Apoptosis 2003;8(5):413–450.

    PubMed  CAS  Google Scholar 

  151. Rowinsky EK. The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Ann Rev Med 1997;48:353–374.

    PubMed  CAS  Google Scholar 

  152. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant anti-tumor agents part 6: the isolation and structure of taxol a novel anti leukemic and anti tumor agent from Taxus brevifolia. J Am Chem Soc 1971;93(9):2325–2327.

    PubMed  CAS  Google Scholar 

  153. Schiff PB, Horwitz SB. Taxol stabilizes micro tubules in mouse fibroblast cells. Proc Natl Acad Sci USA 1980;77(3):1561–1565.

    PubMed  CAS  Google Scholar 

  154. Wang TH, Popp DM, Wang HS, et al. Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-Jun N-terminal kinase (JNK)-dependent and-independent pathways in ovarian cancer cells. J Biol Chem 1999;274(12):8208–8216.

    PubMed  CAS  Google Scholar 

  155. Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC. Clinical toxicities encountered with paclitaxel. Semin Oncol 1993;20(4 Suppl 3):1–15.

    PubMed  CAS  Google Scholar 

  156. Hofle GH, Bedorf N, Steinmetz H, Schomburg D, Gerth K, Reichenbach H. Epothilone A and B-novel 16-membered macrolides with cytotoxic activity—isolation, crystal structure, and conformation in solution. Angew Chem 1996;35(13-14):1567–1569.

    Google Scholar 

  157. Winkler JD, Quinn KJ, MacKinnon CH, Hiscock SD, McLaughlin EC. Tandem Diels-Alder fragmentation approach to the synthesis of eleutherobin. Org Lett 2003;5(10):1805–1808.

    PubMed  CAS  Google Scholar 

  158. Scalabrino G, Sun XW, Mann J, Baron A. A convergent approach to the marine natural product eleutherobin: synthesis of key intermediates and attempts to produce the basic skeleton. Org Biomol Chem 2003;1(2):318–327.

    PubMed  Google Scholar 

  159. Chen XT, Bhattacharya SK, Zhou BS, Gutteridge CE, Pettus TRR, Danishefsky SJ. The total synthesis of eleutherobin. J Am Chem Soc 1999;121(28):6563–6579.

    CAS  Google Scholar 

  160. Nicolaou KC, Xu JY, Kim S, et al. Total synthesis of sarcodictyins A and B. J Am Chem Soc 1998;120(34):8661–8673.

    CAS  Google Scholar 

  161. Britton R, de Silva ED, Bigg CM, McHardy LM, Roberge M, Andersen RJ. Synthetic transformations of eleutherobin reveal new features of its microtubule-stabilizing pharmacophore. J Am Chem Soc 2001;123(35):8632–8633.

    PubMed  CAS  Google Scholar 

  162. Britton R, Roberge M, Berisch H, Andersen RJ. Antimitotic diterpenoids from Erythropodium caribaeorum: isolation artifacts and putative biosynthetic intermediates. Tetrahedron Lett 2001;42(16):2953–2956.

    CAS  Google Scholar 

  163. Cinel B, Patrick BO, Roberge M, Andersen RJ. Solid-state and solution conformations of eleutherobin obtained from X-ray diffraction analysis and solution NOE data. Tetrahedron Lett 2000;41(16):2811–2815.

    CAS  Google Scholar 

  164. Taglialatela-Scafati O, Deo-Jangra U, Campbell M, Roberge M, Andersen RJ. Diterpenolds from cultured Erythropodium caribaeorum. Org Lett 2002;4(23):4085–4088.

    PubMed  CAS  Google Scholar 

  165. Ketzinel S, Rudi A, Schleyer M, Benayahu Y, Kashman Y. Sarcodictyin a and two novel diterpenoid glycosides, eleuthosides a and b, from the soft coral Eleutherobia aurea. J Nat Prod 1996;59(9):873–875.

    CAS  Google Scholar 

  166. Ciomei M, Albanese C, Pastori W, et al. Sarcodictyins: a new class of marine derivatives with mode of action similar to taxol. Proc Am Assoc Cancer Res Annu Meet 1997;38(0):5.

    Google Scholar 

  167. Cinel B, Roberge M, Behrisch H, van Ofwegen L, Castro CB, Andersen RJ. Antimitotic diterpenes from Erythropodium caribaeorum test pharmacophore models for microtubule stabilization. Org Lett 2000;2(3):257–260.

    PubMed  CAS  Google Scholar 

  168. Nicolaou KC, Kim SH, Pfefferkorn J, et al. Synthesis and biological activity of sarcodictyins. Angew Chem 1998;37(10):1418–1421.

    CAS  Google Scholar 

  169. Ata A, Kerr RG, Moya CE, Jacobs RS. Identification of anti-inflammatory diterpenes from the marine gorgonian Pseudopterogorgia elisabethae. Tetrahedron 2003;59(23):4215–4222.

    CAS  Google Scholar 

  170. Haimes HB, Jimenez PA. Use of pseudopterosins for promoting wound healing. Official Gazette of the United States Patent & Trademark Office Patents 1997;1194(4):2589.

    Google Scholar 

  171. Rodriguez AD, Ramirez C. Serrulatane diterpenes with antimycobacterial activity isolated from the West Indian sea whip Pseudopterogorgia elisabethae. J Nat Prod 2001;64(1):100–102.

    PubMed  CAS  Google Scholar 

  172. Rodriguez AD, Ramirez C, Rodriguez, II, Gonzalez E. Novel antimycobacterial benzoxazole alkaloids, from the West Indian sea whip Pseudopterogorgia elisabethae. Org Lett 1999;1(3): 527–530.

    PubMed  CAS  Google Scholar 

  173. Etahiri S, Bultel-Ponce V, Caux C, Guyot M. New bromoditerpenes from the red alga Sphaerococcus coronopifolius. J Nat Prod 2001;64(8):1024–1027.

    PubMed  CAS  Google Scholar 

  174. Cafieri F, De Napoli L, Fattorusso E, Santacroce C. Diterpenes from the red alga Sphaerococcus coronopifolius. Phytochemistry 1987;26(2):471–474.

    CAS  Google Scholar 

  175. Konig GM, Wright AD, Angerhofer CK. Novel potent antimalarial diterpene isocyanates, isothiocyanates, and isonitriles from the tropical marine sponge Cymbastela hooperi. J Org Chem 1996;61(10):3259–3267.

    Google Scholar 

  176. Groweiss A, Look SA, Fenical W. Solenolides new antiinflammatory and antiviral diterpenoids from a marine octocoral of the genus Solenopodium. J Org Chem 1988;53(11):2401–2406.

    CAS  Google Scholar 

  177. Sakemi S, Higa T, Jefford CW, Bernardinelli G. Venustatriol a new anti-viral triterpene tetracyclic ether from Laurencia venusta. Tetrahedron Lett 1986;27(36):4287–4290.

    CAS  Google Scholar 

  178. Komoto S, McConnell OJ, Cross SS. Antiviral Furanoditerpenoids. US Patent-4801607. January 31 1989. Official Gazette of the United States Patent & Trademark Office Patents 1989;1098(5):2452.

    Google Scholar 

  179. Potts BCM, Faulkner DJ, De Carvalho MS, Jacobs RS. Chemical mechanism of inactivation of bee venom phospholipase A-2 by the marine natural products manoalide luffariellolide and scalaradial. J Am Chem Soc 1992;114(13):5093–5100.

    CAS  Google Scholar 

  180. Puliti R, De Rosa S, Mattia CA, Mazzarella L. Structure and stereochemistry of an acetate derivative of cacospongionolide a new antitumoral sesterterpenoid from marine sponge Cacospongia mollior. Acta Crystallog C Crystal Struct Comm 1990;46(8):1533–1536.

    Google Scholar 

  181. De Silva ED, Scheuer PJ. Manoalide an antibiotic sester terpenoid from the marine sponge Luffariella variabilis. Tetrahedron Lett 1980;21(17):1611–1614.

    Google Scholar 

  182. Pommier A, Stepanenko V, Jarowicki K, Kocienski PJ. Synthesis of (+)-manoalide via a copper(I)-mediated 1,2-metalate rearrangement. J Org Chem 2003;68(10):4008–4013.

    PubMed  CAS  Google Scholar 

  183. Soriente A, De Rosa M, Scettri A, et al. Manoalide. Curr Med Chem 1999;6(5):415–431.

    PubMed  CAS  Google Scholar 

  184. Glaser KB, De Carvalho MS, Jacobs RS, Kernan MR, Faulkner DJ. Manoalide structureactivity studies and definition of the pharmacophore for phospholipase A(2) inactivation. Mol Pharmacol 1989;36(5):782–788.

    PubMed  CAS  Google Scholar 

  185. Reynolds LJ, Morgan BP, Hite GA, Mihelich ED, Dennis EA. Phospholipase A-2 inhibition and modification by manoalogue. J Am Chem Soc 1988;110(15):5172–5177.

    CAS  Google Scholar 

  186. Randazzo A, Debitus C, Minale L, et al. Petrosaspongiolides M-R—new potent and selective phospholipase A(2) inhibitors from the new caledonian marine sponge Petrosaspongia nigra. J Nat Prod 1998;61(5):571–575.

    PubMed  CAS  Google Scholar 

  187. Kernan MR, Faulkner DJ, Jacobs RS. The luffariellins novel antiinflammatory sesterterpenes of chemotaxonomic importance from the marine sponge Luffariella variabilis. J Org Chem 1987;52(14):3081–3083.

    CAS  Google Scholar 

  188. Kernan MR, Faulkner DJ, Parkanyi L, Clardy J, De Carvalho MS, Jacobs RS. Luffolide, a novel anti-inflammatory terpene from the sponge Luffariella sp. Experientia 1989;45(4):388–390.

    PubMed  CAS  Google Scholar 

  189. De Rosa S, De Stefano S, Zavodnik N. Cacospongionolide: a new antitumoral sesterterpene from the marine sponge Cacospongia mollior. J Org Chem 1988;53(21):5020–5023.

    Google Scholar 

  190. De Rosa S, Puliti R, Crispino A, De Giulio A, Mattia CA, Mazzarella L. A new scalarane sesterterpenoid from the marine sponge Cacospongia mollior. J Nat Prod 1994;57(2):256–262.

    PubMed  Google Scholar 

  191. De Silva ED, Scheuer PJ. 3 New sester terpenoid antibiotics from the marine sponge Luffariella variabilis. Tetrahedron Lett 1981;22(33):3147–3150.

    Google Scholar 

  192. Albizati KF, Holman T, Faulkner DJ, Glaser KB, Jacobs RS. Luffariellolide: an anti-inflammatory sesterterpene from the marine sponge Luffariella sp. Experientia 1987;43(8):949–950.

    CAS  Google Scholar 

  193. Posadas I, De Rosa S, Terencio MC, Paya M, Alcaraz MJ. Cacospongionolide B suppresses the expression of inflammatory enzymes and tumour necrosis factor-alpha by inhibiting nuclear factor-kappa B activation. Br J Pharmacol 2003;138(8):1571–1579.

    PubMed  CAS  Google Scholar 

  194. Posadas I, Terencio MC, Randazzo A, Gomez-Paloma L, Paya M, Alcaraz MJ. Inhibition of the NF-kappa B signaling pathway mediates the anti-inflammatory effects of petrosaspongiolide M. Biochem Pharmcol 2003;65(5):887–895.

    CAS  Google Scholar 

  195. Garcia-Pastor P, Randazzo A, Gomez-Paloma L, Alcaraz MJ, Paya M. Effects of petrosaspongiolide M, a novel phospholipase A(2) inhibitor, on acute and chronic inflammation. J Pharmacol Exper Ther 1999;289(1):166–172.

    CAS  Google Scholar 

  196. Dal Piaz F, Casapullo A, Randazzo A, et al. Molecular basis of phospholipase A(2) inhibition by petrosaspongiolide M. Chembiochem 2002;3(7):664–671.

    Google Scholar 

  197. Youssef DTA, Yamaki RK, Kelly M, Scheuer PJ. Salmahyrtisol A, a novel cytotoxic sesterterpene from the Red Sea sponge Hyrtios erecta. J Nat Prod 2002;65(1):2–6.

    PubMed  CAS  Google Scholar 

  198. Chinworrungsee M, Kittakoop P, Isaka M, Rungrod A, Tanticharoen M, Thebtaranonth Y. Antimalarial halorosellinic acid from the marine fungus Halorosellinia oceanica. Bioorg Med Chem Lett 2001;11(15):1965–1969.

    PubMed  CAS  Google Scholar 

  199. Renner MK, Jensen PR, Fenical W. Mangicols: structures and biosynthesis of a new class of sesterterpene polyols from a marine fungus of the genus Fusarium. J Org Chem 2000;65(16): 4843–4852.

    PubMed  CAS  Google Scholar 

  200. Nicolaou KC, Sorensen EJ (eds), Classics in Total Synthesis. Weinheim, Germany: VCH, 1996.

    Google Scholar 

  201. Nicolaou KC, Vourloumis D, Winssinger N, Baran PS. The art and science of total synthesis at the dawn of the twenty-first century. Angew Chem Int Ed 2000;39(1):44–122.

    CAS  Google Scholar 

  202. Kingston DGI, Jagtap PG, Yuan H, Samala L. The chemistry of Taxol and related taxoids. Prog Chem Org Nat Prod 2002;84:53–225.

    CAS  Google Scholar 

  203. Holton RA, Kim HB, Somoza C, et al. First total synthesis of Taxol. 2. Completion of the C and D rings. J Am Chem Soc 1994;116(4):1599–1600.

    CAS  Google Scholar 

  204. Holton RA, Somoza C, Kim HB, et al. First total synthesis of Taxol. 1. Functionalization of the B ring. J Am Chem Soc 1994;116(4):1597–1598.

    CAS  Google Scholar 

  205. Nicolaou KC, Yang Z, Liu JJ, et al. Total synthesis of Taxol. Nature 1994;367(6464):630–634.

    PubMed  CAS  Google Scholar 

  206. Masters JJ, Link JT, Snyder LB, Young WB, Danishefsky SJ. A total synthesis of Taxol. Angew Chem Int Ed 1995;34(16):1723–1726.

    CAS  Google Scholar 

  207. Nicolaou KC, Ueno H, Liu JJ, et al. Total synthesis of Taxol. 4. The final stages and completion of the synthesis. J Am Chem Soc 1995;117(2):653–659.

    CAS  Google Scholar 

  208. Nicolaou KC, Nantermet PG, Ueno H, Guy RK, Couladouros EA, Sorensen EJ. Total Synthesis of Taxol. 1. Retrosynthesis, degradation, and reconstitution. J Am Chem Soc 1995;117(2): 624–633.

    CAS  Google Scholar 

  209. Danishefsky SJ, Masters JJ, Young WB, et al. Total synthesis of baccatin III and Taxol. J Am Chem Soc 1996;118(12):2843–2859.

    CAS  Google Scholar 

  210. Wender PA, Badham NF, Conway SP, et al. The pinene path to taxanes. 5. Stereocontrolled synthesis of a versatile taxane precursor. J Am Chem Soc 1997;119(11):2755–2756.

    CAS  Google Scholar 

  211. Wender PA, Badham NF, Conway SP, et al. The pinene path to taxanes. 6. A concise stereocontrolled synthesis of Taxol. J Am Chem Soc 1997;119(11):2757–2758.

    CAS  Google Scholar 

  212. Morihira K, Hara R, Kawahara S, et al. Enantioselective total synthesis of Taxol. J Am Chem Soc 1998;120(49):12,980–12,981.

    CAS  Google Scholar 

  213. Nicolaou KC, Ohshima T, Hosokawa S, et al. Total synthesis of eleutherobin and eleuthosides A and B. J Am Chem Soc 1998;120(34):8674–880.

    CAS  Google Scholar 

  214. Shiina I, Saitoh K, Frechard-Ortuno I, Mukaiyama T. Total asymmetric synthesis of Taxol by dehydration condensation between 7-TES baccatin III and protected N-benzoylphenylisoserines prepared by enantioselective aldol reaction. Chem Lett 1998(1):3–4.

    Google Scholar 

  215. Mukaiyama T, Shiina I, Iwadare H, et al. Asymmetric total synthesis of Taxol. Chem-Euro J 1999;5(1):121–161.

    CAS  Google Scholar 

  216. Kusama H, Hara R, Kawahara S, et al. Enantioselective total synthesis of (-)-Taxol. J Am Chem Soc 2000;122(16):3811–3820.

    CAS  Google Scholar 

  217. Jung M, ElSohly HN, Croom EM, McPhail AT, McPhail DR. Practical conversion of artemisinic acid in desoxyartemisinin. J Org Chem 1986;51(26):5417–5419.

    CAS  Google Scholar 

  218. Roth RJ, Acton N. A simple conversion of artemisinic acid into artemisinin. J Nat Prod 1989;52(5):1183–1185.

    PubMed  CAS  Google Scholar 

  219. Ye B, Wu YL. An efficient synthesis of qinghaosu and deoxoqinghaosu from arteannuic acid. J Chem Soc Chem Comm 1990(10):726–727.

    Google Scholar 

  220. Luo XD, Shen CC. The chemistry, pharmacology, and clinical-applications of qinghaosu (artemisinin) and its derivatives. Med Res Rev 1987;7(1):29–52.

    PubMed  CAS  Google Scholar 

  221. Schmid G, Hofheinz W. Total synthesis of qinghaosu. J Am Chem Soc 1983;105:624–625.

    CAS  Google Scholar 

  222. Soriente A, De Rosa M, Scettri A, et al. Manoalide. Curr Med Chem 1999;6(5):415–431.

    PubMed  CAS  Google Scholar 

  223. Gueritte F. General and recent aspects of the chemistry and structure-activity relationships of taxoids. Curr Pharm Design 2001;7(13):1229–1249.

    CAS  Google Scholar 

  224. Chen X-T, Bhattacharya SK, Zhou B, Gutteridge CE, Pettus TRR, Danishefsky SJ. The total synthesis of eleutherobin. J Am Chem Soc 1999;121(28):6563–6579.

    CAS  Google Scholar 

  225. Chen X-T, Zhou B, Bhattacharya SK, Gutteridge CE, Pettus TRR, Danishefsky SJ. The total synthesis of eleutherobin: a surprise ending. Angew Chem Int Ed 1998;37(6):789–792.

    CAS  Google Scholar 

  226. Nicolaou KC, van Delft F, Ohshima T, et al. Total synthesis of eleutherobin. Angew Chem Int Ed 1997;36(22):2520–2524.

    CAS  Google Scholar 

  227. Nicolaou KC, Winssinger N, Vourloumis D, et al. Solid and solution phase synthesis and biological evaluation of combinatorial sarcodictyin libraries. J Am Chem Soc 1998;120(42): 10,814–10,826.

    CAS  Google Scholar 

  228. Schreiber SL. Target-oriented and diversity-oriented organic synthesis in drug discovery. Science 2000;287(5460):1964–1969.

    PubMed  CAS  Google Scholar 

  229. Burke MD, Berger EM, Schreiber SL. Generating diverse skeletons of small molecules combinatorially. Science 2003;302(5645):613–618.

    PubMed  CAS  Google Scholar 

  230. Appendino G, Tron GC, Jarevng T, Sterner O. Unnatural natural products from the transannular cyclization of lathyrane diterpenes. Org Lett 2001;3(11):1609–1612.

    PubMed  CAS  Google Scholar 

  231. Lucker J, Bouwmeester HJ, Schwab W, Blaas J, van der Plas LHW, Verhoeven HA. Expression of Clarkia S-linalool synthase in transgenic petunia plants results in the accumulation of S-linalyl-beta-D-glucopyranoside. Plant J 2001;27(4):315–324.

    PubMed  CAS  Google Scholar 

  232. Lavy M, Zuker A, Lewinsohn E, et al. Linalool and linalool oxide production in transgenic carnation flowers expressing the Clarkia breweri linalool synthase gene. Mol Breed 2002;9(2):103–111.

    CAS  Google Scholar 

  233. Lewinsohn E, Schalechet F, Wilkinson J, et al. Enhanced levels of the aroma and flavor compound S-linalool by metabolic engineering of the terpenoid pathway in tomato fruits. Plant Physiol 2001;127(3):1256–1265.

    PubMed  CAS  Google Scholar 

  234. Martin VJJ, Yoshikuni Y, Keasling JD. The in vivo synthesis of plant sesquiterpenes by Escherichia coli. Biotech Bioeng 2001;75(5):497–503.

    CAS  Google Scholar 

  235. Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nature Biotechnol 2003.

    Google Scholar 

  236. Wang ZY, Zhong JJ. Repeated elicitation enhances taxane production in suspension cultures of Taxus chinensis in bioreactors. Biotechnol Lett 2002;24(6):445–448.

    Google Scholar 

  237. Zhong JJ. Plant cell culture for production of paclitaxel and other taxanes. J Biosci Bioeng 2002;94(6):591–599.

    PubMed  CAS  Google Scholar 

  238. Liu CZ, Guo C, Wang YC, Ouyang F. Comparison of various bioreactors on growth and artemisinin biosynthesis of Artemisia annua L. shoot cultures. Process Biochem 2003;39(1): 45–49.

    CAS  Google Scholar 

  239. Liu CZ, Guo C, Wang YC, Fan OY. Factors influencing artemisinin production from shoot cultures of Artemisia annua L. World J Microbiol Biotechnol 2003;19(5):535–538.

    CAS  Google Scholar 

  240. Souret FF, Kim Y, Wysiouzil BE, Wobbe KK, Weathers PJ. Scale-up of Artemisia annua L. hairy root cultures produces complex patterns of terpenoid gene expression. Biotech Bioeng 2003;83(6):653–667.

    CAS  Google Scholar 

  241. Wang JW, Tan RX. Artemisinin production in Artemisia annua hairy root cultures with improved growth by altering the nitrogen source in the medium. Biotechnol Lett 2002; 24(14):1153–1156.

    CAS  Google Scholar 

  242. Xie DY, Zou ZR, Ye HC, Li GF, Guo ZC. Selection of hairy root clones of Artemisia annua L. for artemisinin production. Isr J Plant Sci 2001;49(2):129–134.

    CAS  Google Scholar 

  243. Polzin JP, Rorrer GL. Halogenated monoterpene production by microplantlets of the marine red alga Ochtodes secundiramea within an airlift photobioreactor under nutrient medium perfusion. Biotech Bioeng 2003;82(4):415–428.

    CAS  Google Scholar 

  244. Barahona LF, Rorrer GL. Isolation of halogenated monoterpenes from bioreactor-cultured microplantlets of the macrophytic red algae Ochtodes secundiramea and Portieria hornemannii. J Nat Prod 2003;66(6):743–751.

    PubMed  CAS  Google Scholar 

  245. Huang YM, Rorrer GL. Cultivation of microplantlets derived from the marine red alga Agardhiella subulata in a stirred tank photobioreactor. Biotechnol Prog 2003;19(2):418–427.

    PubMed  CAS  Google Scholar 

  246. Huang YM, Rorrer GL. Dynamics of oxygen evolution and biomass production during cultivation of Agardhiella subulata microplantlets in a bubble-column photobioreactor under medium perfusion. Biotechnol Prog 2002;18(1):62–71.

    PubMed  CAS  Google Scholar 

  247. Maliakal S, Cheney DP, Rorrer GL. Halogenated monoterpene production in regenerated plantlet cultures of Ochtodes secundiramea (Rhodophyta, Cryptonemiales). J Phycol 2001;37(6):1010–1019.

    CAS  Google Scholar 

  248. Polzin JJ, Rorrer GL, Cheney DP. Metabolic flux analysis of halogenated monoterpene biosynthesis in microplantlets of the macrophytic red alga Ochtodes secundiramea. Biomol Eng 2003;20(4–6 Special Issue SI):205–215.

    PubMed  CAS  Google Scholar 

  249. Mendola D. Aquaculture of three phyla of marine invertebrates to yield bioactive metabolites: process developments and economics. Biomol Eng 2003;20(4–6 Special Issue SI):441–458.

    PubMed  CAS  Google Scholar 

  250. Ling T, Poupon E, Rueden EJ, Kim SH, Theodorakis EA. Unified synthesis of quinone sesquiterpenes based on a radical decarboxylation and quinone addition reaction. J Am Chem Soc 2002;124(41):12,261–12,267.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hawaii Natural Energy Institute, Department of Oceanography, School of Ocean and Earth Sciences and Technology, University of Hawaii at Manoa, Honolulu, HI

    Guangyi Wang

  2. Department of Chemistry, Stanford University, Stanford, CA

    Weiping Tang

  3. Department of Oceanography, School of Ocean and Earth Sciences and Technology, University of Hawaii at Manoa, Honolulu, HI

    Robert R. Bidigare

Authors
  1. Guangyi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiping Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert R. Bidigare
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

    Lixin Zhang PhD

  2. SynerZ Pharmaceuticals Inc., Lexington, MA

    Lixin Zhang PhD

  3. Charles A. Dana Research Institute (R.I.S.E.), Drew University, Madison, NJ

    Arnold L. Demain PhD

Rights and permissions

Reprints and Permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Wang, G., Tang, W., Bidigare, R.R. (2005). Terpenoids As Therapeutic Drugs and Pharmaceutical Agents. In: Zhang, L., Demain, A.L. (eds) Natural Products. Humana Press. https://doi.org/10.1007/978-1-59259-976-9_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-976-9_9

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-383-1

  • Online ISBN: 978-1-59259-976-9

  • eBook Packages: MedicineMedicine (R0)