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Intensely Sweet Saponin Osladin: Synthetic and Structural Study

  • Mugio Nishizawa
  • Hidetoshi Yamada
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 405)

Abstract

Saccharin, dulcin, sodium cyclamate, acesulfame-K, and aspartame are well-known artificial sweeteners that have been discovered accidentally during some synthetic experiments. Intensely sweet tasting substances are also widely distributed in nature particularly in the plant kingdom. These materials have been an exciting research area for natural product chemists and a variety of sweet-tasting natural products have been characterized.1,2 Many of them are glycosides of terpenoids or steroids. A sweet principle of the Chinese drug Glycyrrhiza glabra (Fabaceae) is the well-known glycyrrhizin (1); it has been used as an auxiliary food additive.3 This glycoside is 150 times sweeter than sucrose. A saponin, mogroside V (2), is 250 times sweeter than sucrose and found in the fruit of a Cucurbitaceaeous plant, Momordica grosvenorii.4 The triterpene glycoside abrusoside B (3) was recently characterized as the sweet principle of Abrus precatorius (Leguminosae),5 and is 100 times sweeter than sucrose. The sweet diterpene glycoside stevioside (4) has been isolated from Paraguayan Composite plant Stevia rebaudiana.6 It is 300 times sweeter than sucrose. Baiyunoside (5) is the sweet principle of a Chinese drug Phlomis betonicoides (Labiatae),7,8 and the labdane-type diterpene glycoside 5 is 250 times sweeter than sucrose. A fern metabolite osladin (6) is the intensely sweet steroidal glycoside isolated from the fern Polypodium vulgare.9 Since these sweet-tasting natural glycosides have not been the subject of organic synthesis, we have been interested in developing synthetic approaches to these natural products. We have developed an effective olefin cyclization agent mercury triflate amine complex, Hg(OS02CF3)2·C6H5NMe2,10–14 that is useful to construct labdane-type diterpenoids.

Keywords

Total Synthesis Triflic Acid Condensation Of29 Diterpene Glycoside Sweet Compound 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    A. D.Kinghorn and D. D. Soejarto, Intensely sweet compounds of natural origin, Med. Res. Rev. 9: 91 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    A. D. Kinghorn and J. Kim, Potently sweet compounds from plants: techniques of isolation and identification, Bioactive Natural Products, Eds. S. M. Colegate and R. J. Molyneux, CRC Press Inc., Boca Raton, FL. pp 173 (1993).Google Scholar
  3. 3.
    B. Lythgoe and S. Trippett, The constitution of the disaccharide of glycyrrhinic acid, J. Chem. Soc. 1983 (1950).Google Scholar
  4. 4.
    T. Takemoto, S. Arihara, T. Nakajima, and M. Okuhira, Studies on the constituents of Fructus Momordicae. I. On the sweet principle, Yakugaku Zasshi 103:1151 (1983).Google Scholar
  5. 5.
    Y. H. Choi, R. A. Hussain, J. M. Pezzuto, D. D. Soejarto, A. D. Kinghorn, and J. F. Morton, Abrusoside A-D, four novel sweet-tasting triterpene glycoside constituents from the leaves of Abrus precatorius, J. Nat. Prod. 52:1118 (1989).PubMedCrossRefGoogle Scholar
  6. 6.
    E. Vis and H. G. Fletcher, Jr., Stevioside IV. Evidence that stevioside is a sophoroside, J. Am. Chem. Soc. 78:4709 (1956).CrossRefGoogle Scholar
  7. 7.
    T. Tanaka, O. Tanaka, Z. W. Lin, J. Zhou, and H. Ageta, Sweet and bitter glycosides of the Chinese plant drug, Bai-Yun-Shen, Chem. Pharm. Bull. 31:780 (1983).Google Scholar
  8. 8.
    T. Tanaka, O. Tanaka, Z. W. Lin, and J. Zhou, Sweet and bitter principles of the Chinese plant drug, Bai-Yun-Shen: Revision of the assignment of the source plant and isolation of two new diterpene glycosides, Chem. Pharm. Bull. 33:4275 (1985).Google Scholar
  9. 9.
    J. Jizba and V. Herout, Isolation of constituents of common polypody rhizomes (Polypodium vulgare L.), Coll. Czech. Chem. Commun. 32:2867 (1967).Google Scholar
  10. 10.
    M. Nishizawa, H. Takenaka, H. Nishide, and Y. Hayashi, A new olefin cyclization agent, mercury(II) triflate/N, jV-dimethylaniline complex, Tetrahedron Lett. 24:2581 (1983).CrossRefGoogle Scholar
  11. 11.
    M. Nishizawa, H. Takenaka, and Y. Hayashi, Synthesis and structure determination of isoaplysis-20, J. Am. Chem. Soc. 106:4290 (1984).CrossRefGoogle Scholar
  12. 12.
    M. Nishizawa, H. Takenaka, and Y. Hayashi, An experimental evidence of the stepwise mechanism in biomimetic olefin cyclization: trapping of cationic intermmediates, J. Am. Chem. Soc. 107:522 (1985).CrossRefGoogle Scholar
  13. 13.
    M. Nishizawa, H. Takenaka, and Y. Hayashi, Chemical simulation of polycyclic diterpenoid biosynthesis using mercury(II) triflate/N, N-dimethylaniline complex: mechanistic aspect of a biomimetic olefin cyclization, J. Org. Chem. 51:806 (1986).CrossRefGoogle Scholar
  14. 14.
    M. Nishizawa, E. Morikuni, K. Asoh, Y. Kan, K.Uenoyama, and H. Imagawa, Preparetion of mercury (II) triflate in acetonitrile and a biomimetic cyclization of farnesyl sulfone, Synlett 169 (1995).Google Scholar
  15. 15.
    M. Nishizawa, H. Yamada, and Y. Hayashi, Biomimetic cyclization of ambliofuran and its analog by using mercury(II) triflate/Af N-dimethylaniline complex: synthesis of ambliol-A, Tetrahedron Lett. 27:187 (1986).CrossRefGoogle Scholar
  16. 16.
    M. Nishizawa, H. Yamada, and Y. Hayashi, Total synthsis of (±)-baiyunol. Tetrahedron Lett. 27:3255 (1986).CrossRefGoogle Scholar
  17. 17.
    M. Nishizawa, H. Yamada, and Y. Hayashi, Cyclization control of ambliofuran analog: effective total synthesis of baiyunol. J. Org. Chem. 52:4878 (1987).CrossRefGoogle Scholar
  18. 18.
    H. Yamada and M. Nishizawa, Total synthesis of baiyunoside by a novel 2’ discriminated glycosidation, Tetrahedron Lett. 28:4315 (1987).CrossRefGoogle Scholar
  19. 19.
    H. Yamada and M. Nishizawa, Synthesis of sweet tasting diterpene glycosides, baiyunoside and analogs, Tetrahedron 48:3021 (1992).CrossRefGoogle Scholar
  20. 20.
    M. Nishizawa and H. Yamada, Chemical synthesis of sweet diterpene glycosides, Pharmacia 27:790(1991).Google Scholar
  21. 21.
    H. Yamada, M. Nishizawa, and C. Katayama, Osladin, a sweet principle of Polypodium vulgare, structure revision, Tetrahedron Lett. 33:4009 (1992).CrossRefGoogle Scholar
  22. 22.
    H. Yamada and M. Nishizawa, Total synthesis of intensely sweet saponin, osladin, Synlett 54(1993).Google Scholar
  23. 23.
    M. Nishizawa and H. Yamada, Synthesis of sweet tasting glycosides, story of osladin, Chemistry Today 60 (1993).Google Scholar
  24. 24.
    M. Nishizawa and H. Yamada, Novel synthetic approaches into intensely sweet glycosides: baiyunoside and osladin, Synlett 785 (1995).Google Scholar
  25. 25.
    J. Jizba, L. Dolejs, V. Herout, and F. Sorm, The structure of osladin, the sweet principle of the rhizomes of Polypodium vulgare L., Tetrahedron Lett. 1329 (1971).Google Scholar
  26. 26.
    M. Havel and V. Cerny, Partial synthesis of osladin aglycone from solasodine, Coll. Czech. Chem. Commun. 40:1579 (1975).Google Scholar
  27. 27.
    N. R. Farnsworth, Current status of sugar substitutes, Cosmetics and Perfumery 88:27 (1973).Google Scholar
  28. 28.
    J. T. Randolph and S. J. Danishefsky, First synthesis of a digitalis saponin. Demonstration of the scope and limitations of a convergent scheme for branched oligosaccharide synthesis by the logic of glycal assembly, J. Am. Chem. Soc. 115:8473 (1993).CrossRefGoogle Scholar
  29. 29.
    D. J. Cram and D. R. Wilson, Studies in stereochemistry. XXXII. Models for 1,2-asymmetric induction, J. Am. Chem. Soc. 85:1245 (1963).CrossRefGoogle Scholar
  30. 30.
    M. Nishizawa, Y. Kan, and H. Yamada, A simple metal free 2’-discriminated glucosidation procedure, Tetrahedron Lett. 29:4597 (1988).CrossRefGoogle Scholar
  31. 31.
    M. Nishizawa, Y. Kan, and H. Yamada, Thermal glycosidation with benzylated glycosyl chlorides: a very simple procedure of glycosidation, Chem. Pharm. Bull. 37:565 (1989).Google Scholar
  32. 32.
    M. Nishizawa, Y. Kan, W. Shimomoto, and H. Yamada, α-Selective thermal glycosidation of rhamnosyl and mannosyl chlorides, Tetrahedron Lett. 31:2431 (1990).CrossRefGoogle Scholar
  33. 33.
    M. Nishizawa, H. Imagawa, Y. Kan, and H. Yamada, Total synthesis of cyclo-L-rhamnohexaose by a stereoselective thermal glycosylation, Tetrahedron Lett. 32:5551 (1991).CrossRefGoogle Scholar
  34. 34.
    M. Nishizawa, H. Imagawa, K. Kubo, and H. Yamada, Improved synthesis of α -cycloawaodorin, Synlett 447 (1992).Google Scholar
  35. 35.
    H. Yamada and M. Nishizawa, Total synthesis and structure revision of intensely sweet saponin osladin, J. Org. Chem. 60:386 (1995).CrossRefGoogle Scholar
  36. 36.
    S. Seo, Y. Tomita, K. Tori, and Y. Yoshimura, Determination of the absolute configuration of a secondary hydroxy group in a chiral secondary alcohol using glycosidation shifts in carbon-13 nuclear magnetic resonance spectroscopy, J. Am. Chem. Soc. 100:3331 (1978).CrossRefGoogle Scholar
  37. 37.
    R. Kasai, M. Okihara, J. Asakawa, K. Mizutani, and O. Tanaka, 13C NMR study of α -and β-anomeric pairs of D-mannopyranosides and L-rhamnopyranosides, Tetrahedron 35:1427 (1979).CrossRefGoogle Scholar
  38. 38.
    M. Nishizawa, S. Kodama, Y. Yamane, K. Kayano, S. Hatakeyama, and H. Yamada, Synthesis and glycosylation shift of l, l’-disaccharides, Chem. Pharm. Bull. 42:982 (1994).PubMedGoogle Scholar
  39. 39.
    E. J. Corey, K. C. Nicolaou, M. Shibasaki, Y. Machida, and C. S. Shiner, Superoxide ion as a synthetically useful oxygen nucleophile, Tetrahedron Lett. 3183 (1975).Google Scholar
  40. 40.
    E. P. Burrows, G. M. Horneys, and E. Caspi, Reassignment of configuration to the 22-hydroxycholesterols. Synthesis of (225)- and (22/R)-3H-cholesterols, J. Org. Chem. 34:103 (1969).PubMedCrossRefGoogle Scholar
  41. 41.
    D. M. Piatak and J. Wicha, Various approaches to the construction of aliphatic side chains of steroids and related compounds, Chem. Rev. 78:199 (1978).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Mugio Nishizawa
    • 1
  • Hidetoshi Yamada
    • 1
  1. 1.Faculty of Pharmaceutical SciencesTokushima Bunri UniversityTokushimaJapan

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