Synlett 2004(2): 0259-0262  
DOI: 10.1055/s-2003-44985
LETTER
© Georg Thieme Verlag Stuttgart · New York

Facile Synthesis of Ginsenoside Ro

Wenjie Penga, Jiansong Suna, Feng Linb, Xiuwen Hana, Biao Yu*b
a State Key Laboratory of Catalyst, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. China
b State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
e-Mail: byu@mail.sioc.ac.cn;
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Publikationsverlauf

Received 3 November 2003
Publikationsdatum:
08. Dezember 2003 (online)

Abstract

Two concise synthetic routes, being different in the glycosylation sequence, toward ginsenoside Ro (1) are developed. These syntheses feature the elaboration of the glucuronide residue at a later stage via the TEMPO-mediated selective oxidation and the installation of AZMB as a benzoylic neighboring participating group capable of being selectively removed afterward.

    References

  • 1a Kondo N. Marumoto Y. Shoji I. Chem. Pharm. Bull.  1971,  19:  1103 
  • 1b

    The saponin 1 was then named after the Japanese name of the plant to be Chikusetsusaponin V.

  • 2 Tanaka O. Kasai R. Saponins of Ginseng and Related Plants, In Progress in the Chemistry of Organic Natural Products   Vol. 46:  Herz W. Grisebach H. Kirby GW. Tamm C. Springer-Verlag; Wien, New York: 1984.  p.1-76  
  • 3a Fagus sylvatica: Romussi G. Bignardi G. Falsone G. Wendisch D. Arch. Pharm.  1987,  320:  153 
  • 3b Hericium erinaceus: Qian F. Du S. Xu G. Li M. Zeng C. Shu Y. Zhongcaoyao  1988,  19:  290 
  • 3c Polyscias scutellaria: Paphassarang S. Raynaud J. Lussignol M. Cabalion P. J. Nat. Prod.  1990,  53:  163 
  • 3d Hemsleya graciliflora: Kasai R. Tanaka T. Nie RL. Miyakoshi M. Zhou J. Tanaka O. Chem. Pharm. Bull.  1990,  38:  1320 
  • 3e H. dolichocarpa: Shi Y. Yang P. Nie R. Yunnan Zhiwu Yanjiu  1990,  12:  460 
  • 3f Wedelia calendulaceae: Govindachari TR. Premila MS. Indian J. Chem., Sect. B  1991,  30:  466 
  • 3g Achyranthes fauriei: Ida Y. Katsumata M. Satoh Y. Shoji J. Planta Med.  1994,  60:  286 
  • 3h A. bidentata: Marouf A. Desbene S. Khanh TC. Wagner H. Correia M. Chauffert B. Lacaille-Dubois MA. Pharmaceutical Biology  2001,  39:  263 
  • 3i Aralia armata: Fang Z. Lei J. Zeng X. Zhiwu Xuebao  1995,  37:  74 
  • 3j A. cordata: Kawai H. Nishida M. Tashiro Y. Kuroganagi M. Ueno A. Satake M. Chem. Pharm. Bull.  1989,  37:  2318 
  • 3k Kochia indica: Mohamed KM. Hasanean HH. Ohtani K. Yamasaki K. Bull. Pharm. Sci., Assiut Univ.  1998,  21:  27 
  • 4 Recently, a polyacetylene ester of Ginsenoside Ro was identified from ginseng, see: Zhang H. Lu Z. Tan GT. Qiu S. Farnsworth NR. Pezzuto JM. Fong HHS. Tetrahedron Lett.  2002,  43:  973 
  • 5 A review listing 192 GOTCAB saponins identified during 1962-1997, see: Tan N. Zhou J. Zhao S. Phytochemistry  1999,  52:  153 
  • 6 Nakamura T. Inoue K. Nojima S. Sankawa U. Shoji J. Kawasaki T. Shibata S. J. Pharmacobio-Dyn.  1979,  2:  374 
  • 7 Atopkina LN. Malinovskaya GV. Elyakov GB. Uvarova NI. Woerdenbag HJ. Koulman A. Pras N. Potier P. Planta Med.  1999,  65:  30 
  • 8a Zhou X.-H. Kasai R. Yoshikawa M. Kitagawa I. Tanaka O. Chem. Pharm. Bull.  1991,  39:  1250 
  • 8b inventors; Wakanuga Pharmaceutical Co., Ltd. Patent JP  59162931.  ; Chem. Abstr. 1984, 102, 67394
  • 9a Matsuda H. Namba K. Fukuda S. Tani T. Kubo M. Chem. Pharm. Bull.  1986,  34:  2100 
  • 9b Nikan K, Jinsen KK, Kubo M, and Korea S. inventors; Patent JP  57163315.  ; Chem. Abstr. 1982, 98, 78132
  • 10a Lee Y.-M. Saito H. Takagi K. Shibata S. Shoji J. Kondo N. Chem. Pharm. Bull.  1977,  25:  1391 
  • 10b Matsuda H. Samukawa K. Kubo M. Planta Med.  1990,  56:  19 
  • 11a Matsuda H. Samukawa K. Kubo M. Planta Med.  1991,  57:  523 
  • 11b Kubo M, and Matsuda H. inventors; Patent JP  04005235.  ; Chem. Abstr. 1992, 116, 158902
  • In fact, only sporadic studies on the synthesis of triterpenoid saponins have been reported, see:
  • 12a Saito S. Sasaki Y. Kuroda K. Hayashi Y. Sumita S. Nagamura Y. Nishida K. Isiguro I. Chem. Pharm. Bull.  1993,  41:  539 
  • 12b Saito S. Ebashi J. Sumita S. Furumoto T. Nagamura Y. Nishida K. Isiguro I. Chem. Pharm. Bull.  1993,  41:  1395 
  • 12c Bliard C. Massiot G. Nazabadioko S. Tetrahedron Lett.  1994,  35:  6107 
  • 12d Atopkina LN. Uvarova NI. Elyakov GB. Carbohydr. Res.  1997,  303:  449 
  • 12e Anufriev VP. Malinovskaya GV. Denisenko VA. Uvarova NI. Elyakov GB. Kim SI. Baek NI. Carbohydr. Res.  1997,  304:  179 
  • 12f Yu B. Xie J. Deng S. Hui Y. J. Am. Chem. Soc.  1999,  121:  12196 
  • 12g Sun J. Han X. Yu B. Carbohydr. Res.  2003,  338:  827 
  • 13 See ref. cited in: Yu B. Zhu X. Hui Y. Org. Lett.  2000,  2:  2539 
  • 14 Deng S. Yu B. Xie J. Hui Y. J. Org. Chem.  1999,  64:  7265 
  • 15 Yu B. Tao H. J. Org. Chem.  2002,  67:  9099 
  • 16a Wada T. Ohkubo A. Mochizuki A. Sekine M. Tetrahedron Lett.  2001,  42:  1069 
  • 16b Love KR. Andrade RB. Seeberger PH. J. Org. Chem.  2001,  66:  8165 
  • 17 Byramova NE. Ovchinnikov MV. Bakinovskii LV. Kochetkov NK. Carbohydr. Res.  1983,  124:  C8 
  • 18 Jiang L. Chan T.-H. J. Org. Chem.  1998,  63:  8035 
  • 19a Magand D. Grandjean C. Doutheau A. Anker D. Shevchik V. Cotte-Pattat N. Robert-Baudouy J. Carbohydr. Res.  1998,  314:  189 
  • 19b Karst N. Jacquinet J.-C. Eur. J. Org. Chem.  2002,  815 
20

All compounds involved in the synthesis have been well characterized. Selected data for 18-20 and 1 are herewith listed. 18: [α]D = 43.8 (c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 8.25 (d, J = 7.7 Hz, 4 H), 7.99 (d, J = 7.1 Hz, 2 H), 7.92-7.80 (m, 7 H), 7.72 (t, J = 8.8 Hz, 4 H), 7.66-7.18 (m, 28 H), 6.00 (t, J = 9.6 Hz, 1 H), 5.96 (d, J = 8.2 Hz, 1 H), 5.78 (dd, J = 9.6, 8.4 Hz, 1 H), 5.71 (t, J = 9.6 Hz, 1 H), 5.66 (t, J = 9.3 Hz, 1 H), 5.58 (t, J = 9.4 Hz, 1 H), 5.41 (dd, J = 9.3, 9.1 Hz, 1 H), 5.39 (t, J = 9.1 Hz, 1 H), 5.26 (s, 1 H), 5.12 (t, J = 9.6 Hz, 1 H), 5.02 (d, J = 7.7 Hz, 1 H), 4.67 (dd, J = 12.1, 3.6 Hz, 1 H), 4.61-4.53 (m, 2 H), 4.52-4.43 (m, 2 H), 4.30-4.19 (m, 2 H), 4.13-4.01 (m, 3 H), 3.68 (m, 1 H), 3.08 (dd, J = 4.5, 3.1 Hz, 1 H), 2.79 (m, 1 H), 2.05, 1.76, 1.09, 0.97, 0.86, 0.84, 0.76, 0.69, 0.43 (9 × s, 3 H each). 13C NMR (75 MHz, CDCl3): δ = 175.7, 170.6, 169.5, 166.2, 165.7, 165.1, 164.8, 143.1, 133.6, 133.5, 133.3, 133.2, 133.0, 129.8, 129.6, 129.2, 128.9, 128.7, 128.3, 122.7, 103.3, 100.6, 91.9, 90.9, 75.3, 72.9, 72.0, 71.1, 70.4, 70.1, 69.4, 68.9, 63.4, 62.8, 62.4, 55.4, 47.4, 46.8, 45.7, 41.5, 41.0, 39.1, 38.9, 38.4, 36.5, 33.7, 33.0, 31.7, 30.5, 29.7, 27.8, 25.8, 25.5, 23.5, 23.3, 22.6, 20.7, 20.4, 18.0, 16.4, 16.3, 15.2. HRESI-MS: m/z [M + Na]+ calcd for C115H118O29Na: 1985.7651; found: 1985.7643. 19: [α]D = 51.1 (c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 8.05-7.82 (m, 13 H), 7.76-7.71 (m, 4 H), 7.64-7.16 (m, 28 H), 6.01 (t, J = 9.6 Hz, 1 H), 5.96 (d, J = 8.0 Hz, 1 H), 5.76 (dd, J = 9.6, 8.4 Hz, 1 H), 5.71 (t, J = 9.6 Hz, 1 H), 5.67-5.61 (m, 2 H), 5.53 (t, J = 8.7 Hz, 1 H), 5.27 (s, 1 H), 5.18 (t, J = 9.2 Hz, 1 H), 5.13 (d, J = 7.7 Hz, 1 H), 4.68 (dd, J = 11.8, 3.7 Hz, 1 H), 4.61-4.45 (m, 4 H), 4.27 (m, 1 H), 4.11 (m, 1 H), 4.04 (t, J = 8.1 Hz, 1 H), 3.88 (m, 1 H), 3.75-3.65 (m, 2 H), 3.38 (m, 1 H), 3.10 (m, 1 H), 2.80 (m, 1 H), 1.11, 0.97, 0.87, 0.84, 0.78, 0.70, 0.43 (7 × s, 3 H each). 13C NMR (75 MHz, CDCl3): δ = 175.7, 167.0, 166.15, 166.07, 165.6, 165.2, 165.1, 164.7, 143.0, 133.9, 133.4, 133.2, 133.0, 129.8, 129.6, 129.0, 128.7, 128.3, 128.2, 122.7, 103.3, 100.8, 91.9, 90.7, 79.4, 75.1, 72.9, 72.0, 70.3, 70.1, 69.4, 63.4, 62.7, 62.4, 55.4, 47.4, 46.8, 45.7, 41.5, 40.9, 39.1, 38.9, 38.4, 36.5, 33.7, 32.9, 31.7, 30.5, 29.6, 27.8, 26.1, 25.4, 23.4, 23.3, 22.6, 18.0, 16.4, 16.3, 15.1. HRESI-MS: m/z [M + Na]+ calcd for C111H114O27Na: 1901.7440; found: 1901.7436. 20: [α]D = 44.4 (c 0.7, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 8.02-7.80 (m, 13 H), 7.78-7.71 (m, 4 H), 7.64-7.19 (m, 28 H), 6.00 (t, J = 9.6 Hz, 1 H), 5.96 (d, J = 7.7 Hz, 1 H), 5.78-5.68 (m, 3 H), 5.64 (t, J = 9.5 Hz, 1 H), 5.44 (t, J = 8.4 Hz, 1 H), 5.27 (s, 1 H), 5.25-5.11 (m, 2 H), 4.75-4.62 (m, 2 H), 4.60-4.44 (m, 3 H), 4.28 (m, 1 H), 4.18-3.95 (m, 4 H), 3.58-2.92 (br s, 1 H), 3.12 (m, 1 H), 2.79 (m, 1 H), 1.26, 1.00, 0.86, 0.84, 0.71, 0.68, 0.42 (7 × s, 3 H each). 13C NMR (75 MHz, CDCl3): δ = 175.6, 166.1, 165.6, 165.2, 165.1, 164.7, 142.9, 133.4, 133.0, 129.8, 129.6, 128.6, 128.3, 128.2, 122.7, 102.9, 100.5, 91.9, 91.0, 72.9, 72.0, 70.3, 69.9, 69.3, 63.4, 62.7, 55.3, 47.3, 46.8, 45.7, 41.5, 40.9, 38.9, 38.8, 38.3, 36.4, 33.7, 32.9, 31.7, 30.5, 29.6, 27.8, 25.4, 23.4, 22.6, 18.0, 16.4, 16.2, 15.1. HRESI-MS: m/z [M + Na]+ calcd for C111H112O28Na: 1915.7232; found: 1915.7197. 1: [α]D = 3 (c 0.35, MeOH) {lit. [1] : [α]D = 2.85 (MeOH)}. 13C NMR (100 MHz, C5D5N): δ = 177.9, 144.9, 126.0, 105.6, 105.4, 96.3, 90.7, 81.8, 78.9, 78.5, 78.3, 78.1, 77.0, 74.4, 73.9, 72.3, 71.6, 63.4, 62.7, 56.6, 48.7, 47.9, 47.0, 42.8, 42.4, 40.6, 40.3, 39.5, 37.6, 34.7, 33.9, 33.2, 31.5, 30.6, 28.9, 28.8, 26.8, 24.4, 19.2, 18.2, 17.4, 16.2. HRESI-MS: m/z [M+ Na]+ calcd for C48H76O19Na: 979.4873; found: 979.4907.