Facile Synthesis of Ginsenoside Ro

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

doi:10.1055/s-2003-44985

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Synlett 2004(2): 0259-0262
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;

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Publication History

Received 3 November 2003
Publication Date:
08 December 2003 (online)

Abstract
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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

References

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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.