Archives of Pharmacal Research

, Volume 25, Issue 6, pp 725–746

Highly sweet compounds of plant origin

Research Article Review

Abstract

The demand for new alternative “low calorie” sweeteners for dietetic and diabetic purposes has increased worldwide. Although the currently developed and commercially used highly sweet sucrose substitutes are mostly synthetic compounds, the search for such compounds from natural sources is continuing. As of mid-2002, over 100 plant-derived sweet compounds of 20 major structural types had been reported, and were isolated from more than 25 different families of green plants. Several of these highly sweet natural products are marketed as sweeteners or flavoring agents in some countries as pure compounds, compound mixtures, or refined extracts. These highly sweet natural substances are reviewed herein.

Key words

Low-Calorie Natural Sweeteners Plants Glycyrrhizin Mogroside V Rebaudio-side A Stevioside Thaumatin Terpenoids Steroids Flavonoids Proteins 

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References

  1. Anonymous, FDA approves new sweetener.Chem. Eng. News, July 15, 30 (2002).Google Scholar
  2. Amoldi, A., Bassoli, A., Borgonovo, G. and Merlini, L., Synthesis and sweet taste of optically active (-)-haematoxylin and of some (±)-haematoxylin derivatives.J. Chem. Soc., Perkin Trans. 1, 2447–2453 (1995).Google Scholar
  3. Auerbach, M. H., Locke, G. and Hendrick, M. E., Alitame. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 31–40 (2001).Google Scholar
  4. Ayafor, J. F. and Connolly, J. D., 2R,3R-(+)-Acetoxy-4’,5-dihydr-oxy-7-methoxyflavanone and 2R,3R-(+)-acetoxy-4’,5,7-trihydr-oxyflavonone: two new 3-acetylated dihydroflavonols fromAframomum pruinosum Gagnepain (Zingiberaceae).J. Chem. Soc, Perkin Trans. 1, 1750–1754 (1981).CrossRefGoogle Scholar
  5. Baek, N.-I., Chung, M.-S., Shamon, L., Kardono, L. B. S., Tsauri, S., Padmawinata, K., Pezzuto, J. M., Soejarto, D. D. and Kinghorn, A. D., Selligueain A, a novel highly sweet proanthocyanidin from the rhizomes ofSelliguea feei. J. Nat. Prod., 56, 1532–1538 (1993).PubMedCrossRefGoogle Scholar
  6. Baek, N.-I., Kennelly, E. J., Kardono, L. B. S., Tsauri, S., Padmawinata, K., Soejarto, D. D. and Kinghorn, A. D., Flavonoids and a proanthocyanidin from rhizomes o.Selliguea feei. Phytochemistry, 36, 513–518 (1994).CrossRefGoogle Scholar
  7. Bassoli, A., Borgonovo, G., Merlini, L. and Morini, G. Design and synthesis of taste active monatin analogues. 2nd IUPAC-International Symposium on Sweeteners, Hiroshima, Japan, November 13–17, 2001, Abstract P-15.Google Scholar
  8. Bassoli, A., Merlini, L. and Morini, G., Isovanillyl sweeteners. From molecules to receptors.Pure Appl. Chem., 74, 1181–1187 (2002).CrossRefGoogle Scholar
  9. Bopp, B. A. and Price, P., Cyclamate. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 63–85 (2001).Google Scholar
  10. Borrego, F. and Montijano, H., Neohesperidin dihydrochalcone. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 87–104 (2001).Google Scholar
  11. Butchko, H. H., Stargel, W. W., Comer, C. P., Mayhew, D. A. and Andress, S. E., Aspartame. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 41–61 (2001).Google Scholar
  12. Choi, Y.-H., Hussain, R. A., Pezzuto, J. M., Kinghorn, A. D. and Morton, J. F.,Abrusosides A-D, four novel sweet-tasting triterpene glycosides from the leaves ofAbrus precatorius. J. Nat. Prod., 52, 1118–1127 (1989a).PubMedCrossRefGoogle Scholar
  13. Choi, Y.-H., Kinghorn, A. D., Shi, Z., Zhang, H. and Teo, B. K., Abrusoside A: a new type of highly sweet triterpene glycoside. J. Chem. Soc., Chem. Commun., 887–888 (1989b).Google Scholar
  14. Chung, M.-S., Kim, N.-C., Long, L., Shamon, L., Ahmad, W.-Y., Sagrero-Nieves, L., Kardono, L. B. S., Kennelly, E. J., Pezzuto, J. M., Soejarto, D. D. and Kinghorn, A. D., Dere-plication of saccharide and polyol constituents of candidate sweet-tasting plants: isolation of the sesquiterpene glycoside mukurozioside lib as a sweet principle o.Sapindus rarak. Phytochem. Anal., 8, 49–54 (1997).CrossRefGoogle Scholar
  15. Dalton, L., Licorice. Root is used worldwide as a flavor and a medicine.Chem. Eng. News, August 12, 37 (2002).Google Scholar
  16. de Klerk, G. J., Nieuwenhuis, M. G. and Beutler, J. J., Lesson of the week: hypokalaemia and hypertension associated with use of liquorice flavoured chewing gum.BMJ, 314, 731–732 (1997).PubMedGoogle Scholar
  17. DeRider, M. L., Kuloglu, E. S., Abildgaard, F., Aceti, D. J., Assadi-Porter, F B., West-Nielsen, M. and Markley, J. L. Brazzein, a potential low-calorie protein sweetener: high-resolution solution structure of the protein determined from multi-dimensional, multi-nuclear magnetic resonance spectroscopy. 2nd IUPAC-International Symposium on Sweeteners, Hiroshima, Japan, November 13–17, 2001, Abstract PL-08.Google Scholar
  18. DuBois, G. E., Nonnutritive sweeteners.Annu. Rep. Med. Chem., 17, 323–332 (1982).CrossRefGoogle Scholar
  19. DuBois, G. E., Bunes, L. A., Dietrich, P. S. and Stephenson, R. A., Diterpenoid sweeteners. Synthesis and sensory evaluation of biologically stable analogues of stevioside.J. Agric. Food Chem., 32, 1321–1325 (1984).CrossRefGoogle Scholar
  20. Duffy, V. B. and Anderson, G. H., Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners.J. Am. Diet. Assoc., 98, 580–587 (1998).PubMedCrossRefGoogle Scholar
  21. Esaki, S., Tanaka, R. and Kamiya, S., Synthesis and taste of certain steviol glycosides.Agric. Biol. Chem., 48, 1831–1834 (1984).Google Scholar
  22. Fenwick, G. R., Lutomski, J. and Nieman, C., Liquorice.Gly-cyrrhiza glabra L. - composition, uses, and analysis.Food Chem., 38, 119–143 (1990).CrossRefGoogle Scholar
  23. Fischer, C. M., Harper, H. J., Henry Jr., W. J., Mohlenkamp Jr., M. J., Romer, K. and Swaine Jr., R. L. (1994). Sweet beverages and sweetener compositions, PCT patent application, WO94-US1690, Feb. 14, 1994.Google Scholar
  24. Fukunaga, Y., Miyata, T., Nakayasu, N., Mizutani, K., Kasai, R. and Tanaka, O., Enzymatic transglucosylation products of stevioside: separation and sweetness evaluation.Agric. Biol. Chem., 53, 1603–1607 (1989).Google Scholar
  25. Fullas, F., Choi, Y.-H., Kinghorn, A. D. and Bunyapraphatsara, N., Sweet-tasting triterpene glycoside constituents o.Abrus fruticulosus. Planta Med., 56, 332–333 (1990).CrossRefGoogle Scholar
  26. Fullas, F., Hussain, R. A., Bordas, E., Pezzuto, J. M., Soejarto, D. D. and Kinghorn, A. D., Gaudichaudiosides A-E, five novel diterpene glycoside constituents from the sweet-tasting plant, Bacchahs gaudichaudiana.Tetrahedron, 47, 8515–8522 (1991).CrossRefGoogle Scholar
  27. Gao, F., Wang, H., Mabry, T. J. and Kinghorn, A. D., Dihydroflavonol sweeteners and other constituents fro.Hymenoxys turneri. Phytochemistry, 29, 2865–2869 (1990).CrossRefGoogle Scholar
  28. Gibbs, B. F., Alli, I. and Mulligan, C., Sweet and taste-modifying proteins: a review.Nutr. Res. (N. Y), 16, 1619–1630 (1996).CrossRefGoogle Scholar
  29. Goldsmith, L. A. and Merkel, C. M., Sucralose. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 185–207 (2001).Google Scholar
  30. Grenby, T. H., Prospects for sugar substitutes.Chem. Br., 27, 342–345 (1991).Google Scholar
  31. Hirono, S., Chou, W.-H., Kasai, R., Tanaka, O. and Tada, T., Sweet and bitter diterpene-glucosides from leaves o.Rubus suavissimus.Chem. Pharm. Bull., 38, 1743–1744 (1990).Google Scholar
  32. Hu, Z. and He, M., Studies on mabinlin, a sweet protein from the seeds o.Capparis masaikai Levl. I. Extraction, purification and some characteristics.Yunnan Zhiwu Yanjiu, 5, 207–212 (1991).Google Scholar
  33. Huan, V. D., Ohtani, K., Kasai, R., Yamasaki, K. and Tuu, N. V., Sweet pregnane glycosides fro.Telosma procumbens.Chem. Pharm. Bull., 49, 453–460 (2001).PubMedCrossRefGoogle Scholar
  34. Hussain, R. A., Lin, Y.-M., Poveda, L. J., Bordas, E., Chung, B. S., Pezzuto, J. M., Soejarto, D. D. and Kinghorn, A. D., Plant-derived sweetening agents: saccharide and polyol constituents of some sweet-tasting plants.J. Ethnopharmacol., 28, 103–115 (1990a).PubMedCrossRefGoogle Scholar
  35. Hussain, R. A., Poveda, L. J., Pezzuto, J. M., Soejarto, D. D. and Kinghorn, A. D., Sweetening agents of plant origin: phenylpropanoid constituents of seven sweet-tasting plants.Econ. Bot., 44, 174–182 (1990b).Google Scholar
  36. Huxtable, R. J., Pharmacology and toxicology of stevioside, rebaudioside A, and steviol. In Kinghorn, A. D. (Ed.).Stevia: the Genus Stevia. Taylor & Francis, London, pp. 161–177 (2002).Google Scholar
  37. Ishikawa, H., Kitahata, S., Ohtani, K., Ikuhara, C. and Tanaka, O., Production of stevioside and rubusoside derivatives by transfructosylation of β-fructofuranosidase.Agric. Biol. Chem., 54, 3137–3143 (1990).Google Scholar
  38. Kamiya, S., Konishi, F. and Esaki, S., Synthesis and taste of some analogs of stevioside.Agric. Biol. Chem., 43, 3553–3557 (1979).Google Scholar
  39. Kaneda, N., Kasai, R., Yamasaki, K. and Tanaka, O., Chemical studies on sweet diterpene-glycosides o.Stevia rebaudiana: conversion of stevioside into rebaudioside A.Chem. Pharm. Bull., 25, 2466–2467 (1977).Google Scholar
  40. Kaneda, N., Lee, I.-S., Gupta, M. P., Soejarto, D. D. and Kinghorn, A. D., (+)-4β-Hydroxyhernandulcin, a new sweet sesquiterpene from the leaves and flowers ofLippia dulcis. J. Nat. Prod., 55, 1136–1141 (1992).PubMedCrossRefGoogle Scholar
  41. Kasai, R., Fujino, H., Kuzuki, T., Wong, W.-H., Goto, C., Yata, N., Tanaka, O., Yasuhara, F. and Yamaguchi, S., Acyclic sesquiterpene oligosaccharides from pericarps o.Sapindus mukurossi.Phytochemistry, 25, 871–876 (1986).CrossRefGoogle Scholar
  42. Kasai, R., Hirono, S., Chou, W.-H., Tanaka, O. and Chen, F.-H., Sweet dihydroflavonol rhamnoside from leaves o.Engelhardtia chrysolepis, a Chinese folk medicine, Huang-qi.Chem. Pharm. Bull., 36, 4167–4170 (1988a).Google Scholar
  43. Kasai, R., Hirono, S., Chou, W.-H., Tanaka, O. and Chen, F.-H., An additional sweet dihydroflavonol glycoside from leaves o. Engelhardtia chrysolepis, a Chinese folk medicine, Huang-qi.Chem. Pharm. Bull., 39, 1871–1872 (1991).Google Scholar
  44. Kasai, R., Matsumoto, K., Nie, R. L., Zhou, J. and Tanaka, O., Glycosides from Chinese medicinal plants.Hemsleya panacisscandens, and structure-taste relationship of cucurbitane glycosides.Chem. Pharm. Bull., 36, 234–243 (1988b).PubMedGoogle Scholar
  45. Kasai, R., Nie, R.-L., Nashi, K., Ohtani, K., Zhou, J., Tao, G.-D. and Tanaka, O., Sweet cucurbitane glycosides from fruits o.Siraitia siamensis (“hi-zi lou-han-kuo”).Agric. Biol. Chem., 53, 3347–3349 (1989).Google Scholar
  46. Kennelly, E. J., Cai, L., Kim, N.-C. and Kinghorn, A. D., Abrusoside E., a further sweet-tasting cycloartane glycoside from the leaves ofAbrus precatorius.Phytochemistry, 41, 1381–1383 (1996a).CrossRefGoogle Scholar
  47. Kennelly, E. J., Cai, L., Long, L., Shamon, L., Zaw, K., Zhou, B.- N., Pezzuto, J. M. and Kinghorn, A. D., Novel highly sweet secodammarane glycosides fro.Pterocarya paliurus.J. Agric. Food Chem., 43, 2602–2607 (1995).CrossRefGoogle Scholar
  48. Kennelly, E. J., Suttisri, R. and Kinghorn, A. D., Novel sweet-tasting saponins of the cycloartane, oleanane, secodammarane, and steroidal types. In Waller, G. R. and Yamasaki, K. (Eds.).Saponins Used in Food and Agriculture. Plenum Press, New York, pp. 13–24 (1996b).Google Scholar
  49. Kim, J., Choi, Y. H. and Choi, Y.-H., Use of stevioside and cultivation ofStevia rebaudiana in Korea. In Kinghorn, A. D. (Ed.).Stevia: the Genus Stevia. Taylor & Francis, London, pp. 196–202 (2002).Google Scholar
  50. Kim, J. and Kinghorn, A. D., Further steroidal and flavonoid constituents of the sweet plant, Polypodium glycyrrhiza.Phytochemistry, 28, 4, 1225–1228 (1989).CrossRefGoogle Scholar
  51. Kim, J., Pezzuto, J. M., Soejarto, D. D., Lang, F. A. and Kinghom, A. D., Polypodoside A, an intensely sweet constituent of the rhizomes ofPolypodium glycyrrhiza.J. Nat. Prod., 51, 1166–1172 (1988).PubMedCrossRefGoogle Scholar
  52. Kim, J. H., Lim, H. J. and Cheon, S. H., Synthesis of (-)-hernan-dulcin and (+)-hemandulcin.Tetrahedron Lett., 43, 4721–4722 (2002).CrossRefGoogle Scholar
  53. Kim, N.-C., Kim, D. S. H. L. and Kinghorn, A. D., New triter-penoids from the leaves o.Abrus precatorius.Nat. Prod. Left., 16, 261–266 (2002).CrossRefGoogle Scholar
  54. Kim, N.-C., Kinghorn, A. D. and Kim, D. S. H. L., Semisynthesis of abrusoside A methyl ester.Org. Lett., 1, 223–224 (1999).PubMedCrossRefGoogle Scholar
  55. Kinghorn, A. D., Overview. In Kinghorn, A. D. (Ed.).Stevia: the Genus Stevia. Taylor & Francis, London, pp. 1–17 (2002).Google Scholar
  56. Kinghorn, A. D. and Compadre, C. M., Less common high-potency sweeteners. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 209–233 (2001).Google Scholar
  57. Kinghorn, A. D., Fullas, F. and Hussain, R. A., Structure-activity relationships of highly sweet natural products. In Atta-ur-Rahman (Ed.).Studies in Natural Product Chemistry. Elsevier Science Publishers, Amsterdam, pp. 3–41 (1995).Google Scholar
  58. Kinghorn, A. D., Kaneda, N., Baek, N.-I., Kennelly, E. J. and Soejarto, D. D., Noncariogenic intense natural sweeteners.Med. Res. Rev., 18, 347–360 (1998).PubMedCrossRefGoogle Scholar
  59. Kinghorn, A. D. and Kennelly, E. J., Discovery of highly sweet compounds from natural sources.J. Chem. Educ., 72, 676–680 (1995).Google Scholar
  60. Kinghorn, A. D., Kim, N.-C. and Kim, D. S. H. L., Terpenoid glycoside sweeteners. In Ikan, R. (Ed.).Naturally Occurring Glycosides: Chemistry, Distribution and Biological Properties. John Wiley and Sons, Chichester, U.K., pp. 399–429 (1999).Google Scholar
  61. Kinghorn, A. D. and Soejarto, D. D., Sweetening agents of plant origin.CRC Crit. Rev. Plant Sci., 4, 79–120 (1986).Google Scholar
  62. Kinghorn, A. D. and Soejarto, D. D., Intensely sweet compounds of natural origin.Med. Res. Rev., 9, 91–115 (1989).PubMedCrossRefGoogle Scholar
  63. Kinghorn, A. D. and Soejarto, D. D., Discovery of terpenoid and phenolic sweeteners from plants.Pure Appl. Chem., 74, 1169–1179 (2002).CrossRefGoogle Scholar
  64. Kinghorn, A. D., Wu, C. D. and Soejarto, D. D., Stevioside. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 167–183 (2001).Google Scholar
  65. Kinjo, J. and Nohara, T., Hepatoprotective oleanane glucuronides in Fabaceae. In Ageta, H., Aimi, N., Ebizuka, Y., Fujita, T. and Honda, G. (Eds.).Towards Natural Medicine Research in the 21st Century. Elsevier, Amsterdam, pp. 237–248 (1998).Google Scholar
  66. Kitagawa, I., Licorice root. A natural sweetener and an important ingredient in Chinese medicine.Pure Appl. Chem., 74, 1189–1198 (2002).CrossRefGoogle Scholar
  67. Kitagawa, I., Sakagami, M., Hashiuchi, F., Zhou, J. L., Yoshikawa, M. and Ren, J., Apioglycyrrhizin and araboglycyrrhizin, two new sweet oleanane-type triterpene oligoglycosides from the root o. Glycyrrhiza inflata.Chem. Pharm. Bull., 37, 551–553 (1989).Google Scholar
  68. Ko, T.-P., Day, J., Greenwood, A. and McPherson, A., Structures of three crystal forms of the sweet protein thaumatin.Acta Crystallogr.D. Biol. Crystallogr., 50D, 813–825 (1994).CrossRefGoogle Scholar
  69. Kohda, H., Kasai, R., Yamasaki, K., Murakami, K. and Tanaka, O., New sweet diterpene glycosides fro. Stevia rebaudiana.Phytochemistry, 15, 981–983 (1976).CrossRefGoogle Scholar
  70. Kohmura, M. and Ariyoshi, Y., Chemical synthesis and characterization of the sweet protein mabinlin II.Biopolymers, 46, 215–223 (1998).PubMedCrossRefGoogle Scholar
  71. Kohmura, M., Mizukoshi, T., Nio, N., Suzuki, E.-I. and Ariyoshi, Y., Structure-taste relationships of the sweet protein monellin.Pure Appl. Chem., 74, 1235–1242 (2002).CrossRefGoogle Scholar
  72. Kohmura, M., Ota, M., Izawa, H., Ming, D., Hellekant, G. and Ariyoshi, Y., Assignment of the disulfide bonds in the sweet protein brazzein.Biopolymers, 38, 553–556 (1996).PubMedCrossRefGoogle Scholar
  73. Konoshima, T. and Takasaki, M., Cancer-chemopreventive effects of natural sweeteners and related compounds.Pure Appl. Chem., 74, 1309–1316 (2002).CrossRefGoogle Scholar
  74. Koyama, E., Kitazawa, K., Ohori, Y., Sakai, N., Izawa, O., Kakegawa, K., Fujino, A. and Ui, M. Intestinal degradation, absorption, and hepatic metabolism of the glycosidic sweeteners, Stevia mixtures. 2nd IUPAC-International Symposium on Sweeteners, Hiroshima, Japan, 2001, Abstract P-12.Google Scholar
  75. Kubo, H., Ohtani, K., Kasai, R., Yamasaki, K., Nie, R.-L. and Tanaka, O., Cucurbitane glycosides fro.Hemsleya panacisscandens rhizomes.Phytochemistry, 41, 1169–1174 (1996).CrossRefGoogle Scholar
  76. Kurihara, Y., Characterization of antisweet substance, sweet proteins, and sweetness-inducing proteins.Crit. Rev. Food Sci.Nutr., 32, 231–252 (1992).PubMedCrossRefGoogle Scholar
  77. Masuda, H., Ohtani, K., Mizutani, K., Ogawa, S., Kasai, R. and Tanaka, O., Chemical study o.Haematoxylon campechianum: a sweet principle and new dibenz[b, d]oxocin derivatives.Chem. Pharm. Bull., 39, 1382–1384 (1991).Google Scholar
  78. Matsui, M., Sofuni, T. and Nohmi, T., Regionally targeted mutagenesis by metabolically-activated steviol; DNA sequence analysis of steviol-induced mutants of guanine phosphori-bosyltransferase (gpt) gene o.Salmonella typhimurium TM677.Mutagenesis, 11, 565–572 (1996).PubMedCrossRefGoogle Scholar
  79. Matsumoto, K., Kasai, R., Ohtani, K. and Tanaka, O., Minor cucurbitane glycosides from fruits o.Siraitia grosvenori (Cucurbitaceae).Chem. Pharm. Bull., 38, 2030–2032 (1990).Google Scholar
  80. Ming, D. and Hellekant, G., Brazzein, a new high-potency thermostable sweet protein fromPentadiplandra brazzeana B.FEBS Lett., 355, 106–108 (1994).PubMedCrossRefGoogle Scholar
  81. Mizutani, K., Kambara, T., Masuda, H., Tamura, Y., Ikeda, T., Tanaka, O., Tokuda, H., Nishino, H., Kozuka, M., Konoshima, T. and Takasaki, M., Glycyrrhetic acid monoglucuronide (MGGR): biological activities. In Ageta, H., Aimi, N., Ebizuka, Y., Fujita, T. and Honda, G. (Eds.).Toward Natural Medicine Research in the 21st. Century. Elsevier, Amsterdam, pp. 225–235 (1998).Google Scholar
  82. Mizutani, K., Kuramoto, T., Tamura, Y., Ohtake, N., Doi, S., Nakamura, M. and Tanaka, O., Sweetness of glycyrrhetic acid 3-O-β-D-monoglucuronide and the related glycosides.Biosci. Biotechnol. Biochem., 58, 554–555 (1994).PubMedGoogle Scholar
  83. Mizutani, K., Miyata, T., Kasai, R., Tanaka, O., Ogawa, S. and Doi, S., Study on improvement of sweeteners of steviol bisglycosides: selective enzymatic transglucosylation of the 13-O-glycosyl moiety.Agric. Biol. Chem., 53, 395–398 (1989).Google Scholar
  84. Mizutani, K. and Tanaka, O., Use ofStevia rebaudiana sweeteners in Japan. In Kinghorn, A. D. (Ed).Stevia: the Genus Stevia. Taylor & Francis, London, pp. 178–195 (2002).Google Scholar
  85. Montmayeur, J.-P. and Matsunami, H., Receptors for bitter and sweet taste.Curr. Opin. Neurobiol., 12, 366–371 (2002).PubMedCrossRefGoogle Scholar
  86. Mori, K. and Kato, M., Synthesis of (6S,1S)-(+)-hemandulcin, a sweetener, and its stereoisomers.Tetrahedron, 42, 5895–5900 (1986).CrossRefGoogle Scholar
  87. Morimoto, S., Nonaka, G.-I. and Nishioka, I., Tannins and related compounds. XXXV. Proanthocyanidins with a doubly linked unit from the root bark o.Cinnamomum sieboldii Meisner.Chem. Pharm. Bull., 33, 4338–4345 (1985).Google Scholar
  88. Nakamura, K., Baker, T J. and Goodman, M., The total synthesis of monatin.Org. Lett., 2, 2967–2970 (2000).PubMedCrossRefGoogle Scholar
  89. Nishizawa, M. and Yamada, H., Intensely sweet saponin osladin: synthetic and structural study. In Waller, G. R. and Yamasaki, K. (Eds.).Saponins Used in Food and Agriculture. Plenum Press, New York, pp. 25–36 (1996).Google Scholar
  90. Nishizawa, M., Yamada, H., Yamaguchi, Y., Hatakeyama, S., Lee, I.-S., Kennelly, E. J., Kim, J. and Kinghorn, A. D., Structure revision of polypodoside A: major sweet principle ofPolypodium glycyrrhiza.Chem. Lett., 1555–1558, 1979 (1994).Google Scholar
  91. O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York (2001).Google Scholar
  92. Ogata, C. M., Gordon, P. F., De Vos, A. M. and Kim, S.-H., Crystal structure of a sweet-tasting protein, thaumatin, at 1.65 Å resolution.J. Mol. Biol., 228, 893–908 (1992).PubMedCrossRefGoogle Scholar
  93. Ohtani, K., Aikawa, Y., Kasai, R., Chou, W.-H., Yamasaki, K. and Tanaka, O., Minor diterpene glycosides from sweet leaves o.Rubus suavissimus. Phytochemistry, 31, 1553–1559 (1992).CrossRefGoogle Scholar
  94. Ohtani, K. and Yamasaki, K., Methods to improve the taste of the sweet principles ofStevia rebaudiana. In Kinghorn, A. D. (Ed.).Stevia: the Genus Stevia. Taylor & Francis, London, pp. 138–159 (2002).Google Scholar
  95. Oobayashi, K., Yoshikawa, K. and Arihara, S., Structural revision of bryonoside and structure elucidation of minor saponins fro.Bryonia dioica.Phytochemistry, 31, 943–946 (1992).PubMedGoogle Scholar
  96. Pearson, R. L., Saccharin. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 147–165 (2001).Google Scholar
  97. Pezzuto, J. M., Compadre, C. M., Swanson, S. M., Nanayakkara, N. P. D. and Kinghorn, A. D., Metabolically activated steviol, the aglycone of stevioside, is mutagenic.Proc. Natl. Acad. Sci. U. S. A., 82, 2478–2482 (1985).PubMedCrossRefGoogle Scholar
  98. Seewald, N., Replacement. A steady diet of growth of sweeteners and fat substitutes.Chem. Week, June 7, 41 (2000).Google Scholar
  99. Shibasato, M., Current status of Stevia sweeteners and its application.Japan Food Sci., 51–58 (1995).Google Scholar
  100. Shu, R. G., Xu, C. R. and Li, L. N., Studies on the sweet principles from the leaves o.Cyclocarya paliurus (Batal.) Iljinsk.Acta Pharmaceutica Sinica, 30, 757–761 (1995).Google Scholar
  101. Stargel, W. W., Mayhew, D. A., Comer, C. P., Andress, S. E. and Butchko, H. H., Neotame. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 129–145 (2001).Google Scholar
  102. Starratt, A. N., Kirby, C. W., Pocs, R. and Brandle, J. E., Rebaudioside F., a diterpene glycoside fromStevia rebaudiana.Phytochemistry, 59, 367–370 (2002).PubMedCrossRefGoogle Scholar
  103. Subamas, A. and Wagner, H., Analgesic and anti-inflammatory activity of the proanthocyanidin shelligueain A fro. Poly-podium feei METT.Phytomedicine, 7, 401–405 (2000).Google Scholar
  104. Suttisri, R., Chung, M.-S., Kinghorn, A. D., Sticher, O. and Hashimoto, Y., Periandrin V, a further sweet triterpene glycoside fromPeriandra dulcis.Phytochemistry, 34, 405–408 (1993).PubMedCrossRefGoogle Scholar
  105. Suttisri, R., Lee, I.-S. and Kinghorn, A. D., Plant-derived triterpenoid sweetness inhibitors.J. Ethnopharmacol., 47, 9–26 (1995).PubMedCrossRefGoogle Scholar
  106. Takemoto, T., Arihara, S., Nakajima, T. and Okuhira, M., Studies on the constituents of Fructus Momordicae. I. On the sweet principle.Yakugaku Zasshi, 103, 1151–1154 (1983a).PubMedGoogle Scholar
  107. Takemoto, T., Arihara, S., Nakajima, T. and Okuhira, M., Studies on the constituents o. Gynostemma pentaphyllum Makino. II. Structures of gypenoside XV-XXI.Yakugaku Zasshi, 103, 1015–1023 (1983b).Google Scholar
  108. Tanaka, N., Orii, R., Ogasa, K., Wada, H., Murakami, T., Sakai, Y. and Chen, CM., Chemical and chemotaxonomical studies of ferns. LXXX. Proanthocyanidins o.Arachniodes sporadosora Nakaike andA. exilis Ching.Chem. Pharm. Bull., 39, 55–59 (1991).Google Scholar
  109. Tanaka, O., Improvement of taste of natural sweeteners.Pure Appl. Chem., 69, 675–683 (1997).CrossRefGoogle Scholar
  110. Terai, T., Ren, H., Mori, G., Yamaguchi, Y. and Hayashi, T., Mutagenicity of steviol and its oxidative derivatives i.Salmonella typhimurium TM677.Chem. Pharm. Bull., 50, 1007–1010 (2002).PubMedCrossRefGoogle Scholar
  111. Toyoda, K., Matsui, H., Shoda, T., Uneyama, C., Takada, K. and Takahashi, M., Assessment of the carcinogenicity of stevioside in F344 rats.Food Chem. Toxicol., 35, 597–603 (1997).PubMedCrossRefGoogle Scholar
  112. Tsopmo, A., Tchuendem, M. H., Ayafor, J. F., Tillequin, F., Koch, M. and Anke, H., 3-Acetoxy-5,7-dihydroxy-4’-methoxyflavanone, a new cytotoxic dihydroflavanol fromAframomum hanburyi K. Schum.Nat. Prod. Lett., 9, 33–37 (1996).Google Scholar
  113. Van der Wel, H., Isolation and characterization of the sweet principles fro.Dioscoreophyllum cumminsii.FEBS Lett., 21, 88–90 (1972).PubMedCrossRefGoogle Scholar
  114. Van der Wel, H., Larson, G., Hladik, A., Hladik, C. M., Hellekant, G. and Glaser, D., Isolation and characterization of pentadin, the sweet principle o.Pentadiplandra brazzeana.Chem. Senses, 14, 75–79 (1989).CrossRefGoogle Scholar
  115. Van der Wel, H. and Loeve, K., Isolation and characterization of thaumatin I and II, the sweet-tasting proteins fro.Thaumatococcus daniellii.Eur. J. Biochem., 31, 221–225 (1972).PubMedCrossRefGoogle Scholar
  116. Van Rossum, T. G. J., De Jong, F. H., Hop, W. C. J., Boomsma, F. and Schalm, S. W., “Pseudoaldosteroidism” induced by intravenous glycyrrhizin treatment of chronic hepatitis C patients.Neth. J. Gastroenterol. Hepatol., 16, 789–795 (2001).CrossRefGoogle Scholar
  117. Vasaenge, M., Liu, B., Welch, C. J., Rolfsen, W. and Bohlin, L., The flavonoid constituents of two Polypodium species (Calaguala) and their effect on the elastase release in human neutrophils.Planta Med., 63, 511–517 (1997).CrossRefGoogle Scholar
  118. Vleggaar, R., Ackerman, L. G. J. and Steyn, R S., Structure elucidation of monatin, a high-intensity sweetener isolated from the plantSchlerochiton ilicifolius.J. Chem. Soc., Perkin Trans. 7, 3095–3098 (1992).CrossRefGoogle Scholar
  119. von Rymon Lipinski, G.-W. and Hanger, L. Y., Acesulfame-K. In O’Brien Nabors, L. (Ed.).Alternative Sweeteners: Third Edition, Revised and Expanded. Marcel Dekker, New York, pp. 13–30 (2001).Google Scholar
  120. Walters, D. E., Prakash, I. and Desai, N., The active conformations of neotame and other high-potency sweeteners.J. Med. Chem., 43, 1242–1245 (2000).PubMedCrossRefGoogle Scholar
  121. Yamada, H. and Nishizawa, M., Syntheses of sweet tasting diterpene glycosides, baiyunoside and analogs.Tetrahedron, 48, 3021–3044 (1992).CrossRefGoogle Scholar
  122. Yamashita, H., Theerasilp, S., Aiuchi, T., Nakaya, K., Nakamura, Y. and Kurihara, Y., Purification and complete amino acid sequence of a new type of sweet protein with taste-modifying activity, curculin.J. Biol. Chem., 265, 15770–15775 (1990).PubMedGoogle Scholar
  123. Yang, D. J., Zhong, Z. C. and Xie, Z. M., Studies on the sweet principles from the leaves o.Cyclocarya paliurus (Batal.) Iljinskaya.Yao Hsueh Hsueh Pao, 27, 841–844 (1992).PubMedGoogle Scholar
  124. Yoshikawa, M., Morikawa, T., Nakano, K., Pongpiriyadacha, Y., Murakami, T. and Matsuda, H., Characterization of new sweet triterpene saponins fro.Albizia myriophylla.J. Nat. Prod., 65, 1638–1642 (2002).PubMedCrossRefGoogle Scholar
  125. Yoshikawa, M., Murakami, T., Ueda, T., Shimoda, H., Yamahara, J. and Matsuda, H., Development of bioactive functions i.Hydrangea dulcis folium. VII. Absolute stereostructures of 3S-phyllodulcin, 3R- and 3S-phyllodulcin glycosides, and3R-and 3S-thunberginol H glycosides from the leaves ofHydrangea macrophylla Seringe var.thunbergii Makino.Heterocycles, 50, 411–418 (1999).CrossRefGoogle Scholar

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© The Pharmaceutical Society of Korea 2002

Authors and Affiliations

  1. 1.Chemistry and Life SciencesResearch Triangle InstituteNorth CarolinaUSA
  2. 2.Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of PharmacyUniversity of Illinois at ChicagoChicagoUSA
  3. 3.University of Illinois at ChicagoChicagoUSA

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