Facile Synthesis of Ginsenoside Ro

Wenjie Peng; Jiansong Sun; Feng Lin; Xiuwen Han; Biao Yu

doi:10.1055/s-2003-44985

LETTER

Facile Synthesis of Ginsenoside Ro

Wenjie Peng^a, Jiansong Sun^a, Feng Lin^b, Xiuwen Han^a, 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;

Abstract

Alle Artikel dieser Rubrik

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.

Key words

ginsenoside Ro - triterpene saponin - synthesis - glycosylation - oxidation

Volltext

Referenzen

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.