Synthesis of 20S-Protopanaxatriol β-D-Glucopyranosides

Article abstract of DOI:10.1007/s10600-019-02618-6

Condensation of 20S-protopanaxatriol (3β,6α,12β,20S-tetrahydroxydammar-24-ene) (1) with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (2) in the presence of Ag₂O in CH₂Cl₂ gave a mixture of acetylated 3-, 12-, 20-, 3,12-di-, and 3,20-di-O-β-D-glucopyranosides 3–7 that was dominated by 3-O-β-Dglucopyranoside tetraacetate 3 (47%). Subsequent deacetylation by sodium methoxide produced free β-D-glucopyranosides 8–12, three of which were identical to chikusetsusaponin-L₁₀, ginsenoside-F₁, and ginsenoside-Ia, which were isolated earlier from leaves of Panax japonicus and P. ginseng. 3-Mono- and 3,12-di-O-β-D-glucopyranosides 8 and 11 were prepared for the first time.

Full text of DOI:10.1007/s10600-019-02618-6

DOI 10.1007/s10600-019-02618-6
Chemistry of Natural Compounds, Vol. 55, No. 1, January, 2019
SYNTHESIS OF 20S-PROTOPANAXATRIOL
β-D-GLUCOPYRANOSIDES
*
L. N. Atopkina and V. A. Denisenko
Condensation of 20S-protopanaxatriol (3β,6α,12β,20S-tetrahydroxydammar-24-ene) (1) with 2,3,4,6-tetra-
O-acetyl-α-D-glucopyranosyl bromide (2) in the presence of Ag O in CH Cl gave a mixture of acetylated
2
2
2
3-, 12-, 20-, 3,12-di-, and 3,20-di-O-β-D-glucopyranosides 3–7 that was dominated by 3-O-β-D-
glucopyranoside tetraacetate 3 (47%). Subsequent deacetylation by sodium methoxide produced free
β-D-glucopyranosides 8–12, three of which were identical to chikusetsusaponin-L , ginsenoside-F , and
10
1
ginsenoside-Ia, which were isolated earlier from leaves of Panax japonicus and P. ginseng. 3-Mono- and
3,12-di-O-β-D-glucopyranosides 8 and 11 were prepared for the first time.
Keywords: dammarane-type triterpenoids, 20S-protopanaxatriol, glycosylation, 20S-protopanaxatriol 3-O-β-D-
glucopyranoside, 20S-protopanaxatriol 12-O-β-D-glucopyranoside, 20S-protopanaxatriol 20-O-β-D-glucopyranoside,
20S-protopanaxatriol 3,20-di-O-β-D-glucopyranoside, 20S-protopanaxatriol 3,12-di-O-β-D-glucopyranoside.
Glycosides of dammarane-type triterpenoids are constituents of Panax ginseng C. A. Meyer (ginseng) extract.
The breadth and variety of their physiological activity are responsible for the unwavering interest in them over many years.
Differences observed in the properties of ginseng glycosides are often associated with the aglycon structures [1, 2]. Dammarane
glycosides from ginseng are divided into two groups depending on their structure: glycosides of 20S-protopanaxadiol
(ginsenoside-Rb , -Rb , -Rb , -Rd, -Rc, -Rg , -F , -Rh , compound K) and of 20S-protopanaxatriol (ginsenoside-Rg , -Rg ,
1
2
3
3
2
2
1
2
-Rf, -Re, -F , -Rh ). A glycoside is assigned to one group or the other based on the presence or absence of a 6α-OH group in
1
1
the aglycon. As a rule, carbohydrates in 20S-protopanaxadiol glycosides are located on C-3 and C-20; in 20S-protopanaxatriol
glycosides, on C-6 and C-20.
Ginsenoside Rh (20S-protopanaxadiol 3-O-β-D-glucopyranoside) [3] and compound K (20S-protopanaxadiol
2
20-O-β-D-glucopyranoside), the main metabolite of ginsenoside-Rb , -Rb , -Rd, and -Rc that is formed by intestinal microflora
1
2
[4], are the most studied of 20S-protopanaxadiol glycosides with respect to properties and mechanism of action. Preparative
syntheses of these compounds via chemical transformation of betulafolientriol, a constituent of Betula leaf extract [5], were
developed by us. Their biological activity was investigated [6–8].
20S-Protopanaxatriol glycosides have less pronounced cytotoxic and antiproliferative activity against tumor cells
than 20S-protopanaxadiol glycosides [6, 9]. Although the cytotoxicity of 20S-protopanaxatriol 20-O-β-D-glucoside (ginsenoside
F ) for GLC carcinoma and COLO 320 adenocarcinoma human tumor cells was much weaker than that of 20S-protopanaxadiol
1
4
20-O-β-D-glucoside (compound K) [6], ginsenoside F suppressed proliferation of B16 melanoma cells [10] and protected
1
human keratinocytes from UV-radiation-induced apoptosis [11]. The biological activity of chikusetsusaponin-L and
10
ginsenoside-Ia has not been reported.
The present article studied the synthesis of dammarane-type tetracyclic triterpenoid glycosides in order to produce
20S-protopanaxatriol glycosides.
The multitude of dammarane-type triterpenoids isolated from Betula leaves did not comprise compounds with a C-6
OH group that could be potential starting materials for synthesizing 20S-protopanaxatriol glycosides. Therefore, the starting
compound for the glycosylation was 3β,6α,12β,20S-tetrahydroxydammar-24-ene (1), the native genin of ginsenoside-Rg ,
1
-Rg , -Re, and -Rf [12].
2
G. B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch, Russian Academy of Sciences, 159
Prosp. 100 Let Vladivostoku, Vladivostok, 690022, e-mail: atopkina@mail.ru. Translated from Khimiya Prirodnykh Soedinenii,
No. 1, January–February, 2019, pp. 71–75. Original article submitted March 7, 2018.
©
82
0009-3130/19/5501-0082 2019 Springer Science+Business Media, LLC

OR
3
24
R O21
2
12
26
20
1: R = R = R = H; 3: R = GlcAc , R = R = H
1
2
3
1
4
2
3
27
19
18
4: R = R = H, R = GlcAc ; 5: R = R = H, R = GlcAc
1
3
2
4
1
2
3
4
6: R = R = GlcAc , R = H; 7: R = R = GlcAc , R = H
1
2
4
3
1
3
4
2
3
30
8: R = Glc, R = R = H; 9: R = R = H, R = Glc
6
1
2
3
1
3
2
R O
1
10: R = R = H, R = Glc; 11: R = R = Glc, R = H
1
2
3
1
2
3
OH
29
28
12: R = R = Glc, R = H
1
3
2
1, 3 - 12
Condensation of tetraol 1 with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (2) in the presence of Ag O in
2
CH Cl gave a mixture of acetylated 3-, 12-, 20-, 3,12-di-, and 3,20-di-O-β-D-glucopyranosides 3–7 in overall yield 93.8%
2
2
with 3-O-β-D-glucopyranoside 3 dominating (47%). Compounds with glucose on the C-6 OH were not detected by us in
the glycosylation products of 1.
Deacetylation of 3–7 by NaOMe solution (0.1 N) in MeOH at 25°C for 1 h gave in quantitative yield the free
β-D-glucopyranosides 8–12, three of which (12-, 20-, and 3,20-di-O-β-D-glucopyranosides 9, 10, and 12) were identical to
chikusetsusaponin-L from P. japonicus leaves [13] and ginsenoside-F and -Ia from P. ginseng leaves [14, 15].
10
1
13
The structures of all compounds were elucidated using IR, PMR, C NMR, and 2D spectroscopy (COSY, NOESY,
HSQC, HMBC, HSQC-TOCSY). C NMR spectra of 9, 10, and 12 taken in C H N solutions agreed with those published
13
5
5
[13–15]. PMR spectra of all synthesized 20S-protopanaxatriol β-D-glucopyranosides were fully assigned for the first time.
Anomeric protons of acetylated glucose residues in glycosides 3–7 appeared in PMR spectra in CDCl as doublets at
3
δ 4.535–4.558 for C-3; 4.734, C-12; and 4.852–4.858 ppm, C-20; in free glucosides 8–12 in PMR spectra in C H N,
5
5
at δ 5.001–5.013 for C-3; 5.268–5.292, C-12; and 5.191–5.193 ppm, C-20. Chemical shifts and spin–spin coupling constants
of glucose anomeric protons (J = 7.7–8.1 Hz) were indicative of a trans-glycoside bond in all synthesized glycosides.
13
The sites of attachment of the glucose residues were confirmed using C NMR spectra of 1 and 3–12.
Thus, the 3β-OH group was most reactive for glycosylation of 20S-protopanaxatriol (1) under Koenigs–Knorr reaction
conditions. However, the 6α-OH group remained inert. Five 20S-protopanaxatriol β-D-glucopyranosides 8–12 were synthesized.
Three of them (9, 10, 12) were identical to natural glycosides CL , G-F , and G-Ia, which were isolated earlier from
10
1
P. japonicus and P. ginseng leaves [13–15]. 3-Mono- and 3,12-di-O-β-D-glucopyranosides 8 and 11 were prepared for the
first time.
EXPERIMENTAL
13
PMR and C NMR spectra of 1 and 3–7 in CDCl were recorded at 30°C on a Bruker Avance-500 spectrometer at
3
1
13
operating frequency 500 MHz for H and 125 MHz for C; of 8–12, on a Bruker Avance-700 spectrometer at operating
frequency 700 MHz for H and 176 MHz for C in C H N. Chemical shifts were given vs. TMS. Multiplicities of
C resonances were found from DEPT-135 experiments using the standard procedure. Homonuclear 2D H– H COSY-45
1
13
5
5
13
1
1
and NOESY correlation spectra and 2D heteronuclear HSQC and HMBC correlation spectra were also recorded using the
n
standard procedures. HMBC experiments were optimized for J ≅ 5 Hz. IR spectra were recorded from CHCl solutions on
HC
3
a Bruker Vector 22 spectrophotometer. Optical rotation was determined in 10-cm cuvettes at 20°C on a PerkinElmer 343
polarimeter. Melting points were measured on a Boetius apparatus. Column chromatography used KSK silica gel
(120–150 mesh) and solvent systems C H –MeOH (100:1→50:1). The purity of compounds was monitored by TLC on Silica
6
6
Gel 60 F
plates (Merck) using hexane–Me CO (2:1, 1; 3:2, 2) and C H –CHCl –MeOH (6:4:1, 3; 3:2:1, 4; 2:1:1, 5).
254
2 6 6 3
Detection used H SO (10%) in EtOH with heating at 100–200°C. Elemental analyses of all newly synthesized compounds
2
4
agreed with those calculated.
3β,6α,12β,20S-Tetrahydroxydammar-24-ene (20S-protopanaxatriol) (1). Mp 196–198°C (hexane–Me CO),
2
20
21
1
[α] +42.5° (c 0.8, ÑÍÑl ), R 0.20 (1), 0.28 (2), 0.54 (4), 0.70 (5). Lit. [12]: [α] +42.9° (CHCl ). Í NMR spectrum
D
3
f
D
3
(700 MHz, CDCl , δ, ppm, J/Hz): 0.912 (3Í, s, Me-30), 0.936 (3Í, s, Me-19), 0.987 (3Í, s, Me-29), 1.070 (3Í, s, Me-18),
3
1.198 (3Í, s, Me-21), 1.317 (3Í, s, Me-28), 1.633 (3Í, s, Me-27), 1.694 (3Í, s, Me-26), 3.184 (1Í, dd, J = 11.8, 4.7, Í-3α),
13
3.586 (1Í, td, J = 10.3, 5.3, Í-12α), 4.108 (1Í, td, J = 10.5, 3.9, Í-6β), 5.157 (1Í, t, J = 7.0, Í-24). C NMR spectrum
(176 MHz, CDCl , δ, ppm): 15.48 (C-29), 16.83 (C-30), 17.15 (C-19), 17.24 (C-18), 17.74 (C-27), 22.32 (C-23), 25.73
3
83

(C-26), 26.43 (C-16), 26.99 (C-2), 27.04 (C-21), 30.86 (C-28), 30.93 (C-15), 30.98 (C-11), 34.31 (C-22), 38.76 (C-1), 39.15
(C-10), 39.26 (C-4), 40.96 (C-8), 46.96 (C-7), 47.48 (C-13), 49.51 (C-9), 51.39 (C-14), 53.35 (C-17), 61.12 (C-5), 68.65
(C-6), 70.68 (C-12), 74.61 (C-20), 78.57 (C-3), 124.78 (C-24), 132.00 (C-25).
Condensation of Tetraol 1 with 2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosyl Bromide (2). A mixture of tetraol 1
(307 mg, 0.645 mmol), Ag O (468 mg, 2.0 mmol), and α-acetobromoglucose 2 (822 mg, 2.0 mmol) in CH Cl (7 mL) was
2
2
2
continuously stirred at 25°C for 2 h until 2 disappeared (TLC monitoring using C H –CHCl –MeOH, 6:4:1), diluted with
6
6
3
CHCl , and filtered to remove insoluble Ag compounds. The solvent was distilled at reduced pressure. The residue was
3
worked up three times with hot H O to remove water-soluble glucose derivatives, dried, and chromatographed over a column
2
(l 0.35 m, d 30 mm) of silica gel (105 g) with elution (210 mL/h) by C H –MeOH [100:1 (80 × 50 mL) → 50:1 (50 × 50 mL)]
6
6
to afford 7 (1000 mL, 74 mg, 10.1%), 6 (1000 mL, 74 mg, 10.1%), 3 (2000 mL, 245 mg, 47.1%), 5 (1000 mL, 38 mg, 7.3%),
and 4 (1500 mL, 100 mg, 19.2%).
3β-(2′,3′,4′,6′-Tetra-O-acetyl-β-D-glucopyranosyloxy)-6α,12β,20S-trihydroxydammar-24-ene (3). C H O ,
44 70 13
21
–1
mp 219–221°Ñ (EtOH), [α] +23.9° (c 0.8, ÑÍÑl ), R 0.23 (1), 0.35 (2), 0.46 (3), 0.81 (5). IR spectrum (ν, cm ): 1755
(ÑÍ Ñ=Î), 3372 (ÎÍ), 3603 (ÎÍ). Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.902 (3Í, s, Me-30), 0.932 (3Í, s,
D
3
f
1
3
3
Me-19), 0.946 (3Í, s, Me-29), 1.063 (3Í, s, Me-18), 1.202 (3Í, s, Me-21), 1.236 (3Í, s, Me-28), 1.634 (3Í, s, Me-27), 1.694
(3Í, s, Me-26), 2.003, 2.022, 2.026, 2.075 (3Í each, s, ÎÀñ), 3.051 (1Í, dd, J = 11.6, 4.8, Í-3α), 3.582 (1Í, td, J = 10.4, 10.4,
5.3, Í-12α), 3.684 (1Í, ddd, J = 10.0, 5.4, 2.6, Í-5′), 4.091 (1H, m, Í-6β), 4.118 (1Í, dd, J = 12.1, 2.6, H-6a′), 4.242 (1Í, dd,
J = 12.1, 5.5, H-6b′), 4.537 (1Í, d, J = 8.0, H-1′), 5.040 (1Í, t, J = 9.7, H-4′), 5.048 (1Í, dd, J = 9.7, 8.0, H-2′), 5.160 (1Í, m,
13
Í-24), 5.207 (1Í, t, J = 9.7, Í-3′). C NMR spectrum (125 MHz, CDCl , δ, ppm): 16.24 (C-29), 16.80 (C-30), 17.05 (C-19),
3
17.25 (C-18), 17.74 (C-27), 20.58, 20.60, 20.67, 20.74 (4CH CO), 22.32 (C-23), 25.65 (C-2), 25.73 (C-26), 26.41 (C-16),
3
27.12 (C-21), 30.46 (C-28), 30.90 (C-15), 30.95 (C-11), 34.23 (C-22), 38.63 (C-10), 38.71 (C-1), 39.43 (C-4), 40.89 (C-8),
47.01 (C-7), 47.53 (C-13), 49.47 (C-9), 51.37 (C-14), 53.30 (C-17), 61.27 (C-5), 62.25 (C-6′), 68.40 (C-6), 68.79 (C-4′), 70.67
(C-12), 71.54 (C-5′), 71.61 (C-2′), 72.80 (C-3′), 74.73 (C-20), 90.39 (C-3), 103.29 (C-1′), 124.70 (C-24), 132.13 (C-25),
169.21, 169.41, 170.34, 170.61 (4CH CO).
3
12β-(2′,3′,4′,6′-Tetra-O-acetyl-β-D-glucopyranosyloxy)-3β,6α,20S-trihydroxydammar-24-ene (4). C H O ,
44 70 13
20
–1
amorph., [α] +23.3° (c 0.8, ÑÍÑl ), R 0.18 (1), 0.28 (2), 0.26 (3), 0.74 (5). IR spectrum (ν, cm ): 1758 (ÑÍ Ñ=Î), 3474
(ÎÍ), 3606 (ÎÍ). Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.920 (3Í, s, Me-30), 0.934 (3Í, s, Me-19), 0.997
D
3
f
3
1
3
(3Í, s, Me-29), 1.055 (3Í, s, Me-18), 1.110 (3Í, s, Me-21), 1.330 (3Í, s, Me-28), 1.641 (3Í, s, Me-27), 1.702 (3Í, s, Me-26),
1.989, 2.012, 2.026, 2.089 (3Í each, s, ÎÀñ), 3.204 (1Í, dd, J = 11.8, 4.5, Í-3α), 3.671 (1Í, dt, J = 10.0, 3.8, Í-5′), 3.812
(1Í, td, J = 10.6, 5.1, Í-12α), 4.106 (1H, dt, J = 10.5, 3.7, Í-6β), 4.218 (2Í, d, J = 3.8, 2H-6′), 4.734 (1Í, d, J = 8.0, H-1′), 4.901
13
(1Í, dd, J = 9.6, 8.0, H-2′), 5.087 (1Í, t, J = 9.7, H-4′), 5.168 (1Í, tt, J = 7.1, 1.4, Í-24), 5.215 (1Í, t, J = 9.5, Í-3′). C NMR
spectrum (125 MHz, CDCl , δ, ppm): 15.46 (C-29), 17.20 (C-19), 17.29 (C-18), 17.33 (C-30), 17.66 (C-27), 20.54, 20.56,
3
20.65, 20.78 (4CH CO), 22.23 (C-23), 25.77 (C-26), 26.20 (C-21), 26.77 (C-16), 26.83 (C-2), 27.22 (C-11), 30.81 (C-28),
3
31.00 (C-15), 35.84 (C-22), 38.88 (C-1), 39.19 (C-10), 39.31 (C-4), 40.82 (C-8), 45.54 (C-13), 46.71 (C-7), 49.33 (C-9),
51.90 (C-14), 53.22 (C-17), 61.06 (C-5), 61.82 (C-6′), 68.41 (C-6), 68.52 (C-4′), 71.38 (C-2′), 72.04 (C-5′), 72.67 (C-3′),
72.73 (C-20), 77.89 (C-12), 78.43 (C-3), 96.53 (C-1′), 125.72 (C-24), 130.74 (C-25), 168.56, 169.24, 170.35, 170.67 (4CH CO).
3
20S-(2′,3′,4′,6′-Tetra-O-acetyl-β-D-glucopyranosyloxy)-3β,6α,12β-trihydroxydammar-24-ene (5). C H O ,
44 70 13
20
–1
amorph., [α] +22.9° (c 0.75, ÑÍÑl ), R 0.18 (1), 0.28 (2), 0.31 (3), 0.74 (5). IR spectrum (ν, cm ): 1756 (ÑÍ Ñ=Î), 3478
(ÎÍ), 3606 (ÎÍ). Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.890 (3Í, s, Me-30), 0.928 (3Í, s, Me-19), 0.987 (3Í,
D
3
f
3
1
3
s, Me-29), 1.055 (3Í, s, Me-18), 1.265 (3Í, s, Me-21), 1.318 (3Í, s, Me-28), 1.595 (3Í, s, Me-27), 1.666 (3Í, s, Me-26),
1.997, 2.016, 2.039, 2.043 (3Í each, s, ÎÀñ), 3.183 (1Í, dd, J = 11.6, 4.8, Í-3α), 3.532 (1Í, td, J = 10.1, 5.6, Í-12α), 3.676
(1Í, dt, J = 10.0, 4.3, Í-5′), 4.107 (1H, td, J = 10.2, 4.9, Í-6β), 4.125 (2Í, d, J = 4.3, 2H-6′), 4.858 (1Í, d, J = 8.0, H-1′), 4.902
13
(1Í, dd, J = 9.2, 8.0, H-2′), 5.024 (1Í, t, J = 9.7, H-4′), 5.072 (1Í, m, Í-24), 5.226 (1Í, m, J = 9.2, Í-3′). C NMR spectrum
(125 MHz, CDCl , δ, ppm): 15.48 (C-29), 16.99 (C-30), 16.99 (C-19), 17.28 (C-18), 17.70 (C-27), 20.55, 20.59, 20.62, 20.75
3
(4CH CO), 22.20 (C-21), 22.78 (C-23), 25.63 (C-26), 26.34 (C-16), 27.03 (C-2), 29.82 (C-11), 30.19 (C-15), 30.89 (C-28),
3
35.17 (C-22), 38.64 (C-1), 39.18 (C-10), 39.23 (C-4), 40.94 (C-8), 46.87 (C-7), 48.15 (C-13), 49.15 (C-9), 51.00 (C-14), 52.58
(C-17), 61.10 (C-5), 62.37 (C-6′), 68.57 (C-4′), 68.70 (C-6), 69.89 (C-12), 71.94 (C-5′), 72.06 (C-2′), 72.98 (C-3′), 78.59
(C-3), 84.97 (C-20), 94.66 (C-1′), 124.35 (C-24), 131.58 (C-25), 168.96, 169.32, 170.38, 170.64 (4CH CO).
3
3β,12β-Di-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)-6α,20S-dihydroxydammar-24-ene (6). C H O ,
58 88 22
20
–1
amorph., [α] +13.2° (c 4.2, ÑÍÑl ), R 0.20 (1), 0.34 (2), 0.52 (3), 0.83 (5). IR spectrum (ν, cm ): 1756 (ÑÍ Ñ=Î), 3475
(ÎÍ), 3602 (ÎÍ). Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.908 (3Í, s, Me-30), 0.925 (3Í, s, Me-19), 0.948
D
3
f
3
1
3
84

(3Í, s, Me-29), 1.044 (3Í, s, Me-18), 1.105 (3Í, s, Me-21), 1.245 (3Í, s, Me-28), 1.638 (3Í, s, Me-27), 1.699 (3Í, s, Me-26),
1.984, 2.009, 2.009, 2.022, 2.028, 2.034, 2.087, 2.104 (3Í each, s, ÎÀñ), 3.059 (1Í, dd, J = 11.9, 4.8, Í-3α), 3.663 (1H, m,
Í-5′′), 3.676 (1H, m, Í-5′), 3.809 (1Í, td, J = 10.6, 5.1, Í-12α), 4.087 (1H, m, Í-6β), 4.218 (4H, m, 2H-6′, 2H-6′′), 4.558
(1Í, d, J = 8.0, H-1′), 4.734 (1Í, d, J = 8.1, H-1′′), 4.897 (1Í, dd, J = 9.6, 8.1, H-2′′), 5.056 (1Í, dd, J = 9.6, 8.0, H-2′), 5.089
(1Í, t, J = 9.6, H-4′), 5.103 (1Í, t, J = 9.6, H-4′′), 5.166 (1Í, tt, J = 7.1, 1.4, Í-24), 5.210 (1Í, t, J = 9.6, Í-3′′), 5.216 (1Í, t,
13
J = 9.6, Í-3′). C NMR spectrum (125 MHz, CDCl , δ, ppm): 16.22 (C-29), 17.11 (C-19), 17.29 (C-30), 17.31 (C-18), 17.66
3
(C-27), 20.53, 20.54, 20.58, 20.60, 20.64, 20.66, 20.78, 20.78 (8CH CO), 22.23 (C-23), 25.60 (C-2), 25.77 (C-26), 26.22
3
(C-21), 26.74 (C-16), 27.19 (C-11), 30.41 (C-28), 30.95 (C-15), 35.86 (C-22), 38.76 (C-10), 38.82 (C-1), 39.51 (C-4), 40.77
(C-8), 45.55 (C-13), 46.78 (C-7), 49.31 (C-9), 51.85 (C-14), 53.29 (C-17), 61.19 (C-5), 61.79 (C-6′′), 61.87 (C-6′), 68.18 (C-6),
68.58 (C-4′′), 68.61 (C-4′), 71.37 (C-2′′), 71.55 (C-5′), 71.61 (C-2′), 71.97 (C-5′′), 72.64 (C-20), 72.68 (C-3′′), 72.73 (C-3′),
77.71 (C-12), 89.87 (C-3), 96.46 (C-1′′), 103.34 (C-1′), 125.73 (C-24), 130.71 (C-25), 168.54, 169.19, 169.21, 169.35, 170.27,
170.30, 170.61, 170.64 (8CH CO).
3
3β,20S-Di-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)-6α,12β-dihydroxydammar-24-ene (7). C H O ,
58 88 22
20
–1
amorph., [α] +18.7° (c 0.8, ÑÍÑl ), R 0.18 (1), 0.31 (2), 0.61 (3), 0.85 (5). IR spectrum (ν, cm ): 1756 (ÑÍ Ñ=Î), 3474
(ÎÍ), 3606 (ÎÍ). Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.876 (3Í, s, Me-30), 0.921 (3Í, s, Me-19), 0.945 (3Í,
D
3
f
3
1
3
s, Me-29), 1.045 (3Í, s, Me-18), 1.234 (3Í, s, Me-28), 1.258 (3Í, s, Me-21), 1.593 (3Í, s, Me-27), 1.665 (3Í, s, Me-26),
1.996, 2.003, 2.015, 2.023, 2.023, 2.035, 2.040, 2.077 (3Í each, s, ÎÀñ), 3.050 (1Í, dd, J = 11.6, 4.8, Í-3α), 3.582 (1Í, td,
J = 10.3, 5.6, Í-12α), 3.674 (1Í, dt, J = 10.2, 4.2, Í-5′′), 3.692 (1Í, ddd, J = 10.0, 5.6, 2.6, Í-5′), 4.088 (1H, m, Í-6β), 4.112
(1Í, dd, J = 12.2, 2.6, Ha-6′), 4.122 (2Í, d, J = 4.5, 2H-6′′), 4.252 (1Í, dd, J = 12.2, 5.8, Hb-6′), 4.327 (1H, s, 12-OH), 4.535
(1Í, d, J = 7.8, H-1′), 4.852 (1Í, d, J = 7.8, H-1′′), 4.899 (1Í, dd, J = 9.5, 7.8, H-2′′), 5.018 (1Í, t, J = 9.7, H-4′′), 5.032 (1Í,
t, J = 9.7, H-4′), 5.050 (1Í, dd, J = 9.7, 7.8, H-2′), 5.069 (1Í, m, Í-24), 5.207 (1Í, t, J = 9.7, Í-3′), 5.223 (1Í, t, J = 9.7,
13
Í-3′′). C NMR spectrum (125 MHz, CDCl , δ, ppm): 16.26 (C-29), 16.89 (C-19), 16.94 (C-30), 17.30 (C-18), 17.70 (C-27),
3
20.54, 20.58, 20.59, 20.61, 20.62, 20.67, 20.74, 20.74 (8CH CO), 22.25 (C-21), 22.83 (C-23), 25.63 (C-2), 25.63 (C-26),
3
26.31 (C-16), 29.84 (C-11), 30.18 (C-15), 30.49 (C-28), 35.16 (C-22), 38.53 (C-1), 38.73 (C-10), 39.40 (C-4), 40.87 (C-8), 46.90
(C-7), 48.15 (C-13), 49.12 (C-9), 50.98 (C-14), 52.63 (C-17), 61.26 (C-5), 62.31 (C-6′′), 62.34 (C-6′), 68.45 (C-6), 68.55 (C-4′′),
68.82 (C-4′), 69.88 (C-12), 71.55 (C-5′), 71.63 (C-2′), 71.98 (C-5′′), 72.08 (C-2′′), 72.83 (C-3′), 72.92 (C-3′′), 84.91 (C-20),
90.50 (C-3), 94.67 (C-1′′), 103.27 (C-1′), 124.31 (C-24), 131.61 (C-25), 168.96, 169.19, 169.30, 169.41, 170.34, 170.37,
170.62, 170.63 (8CH CO).
3
3β,6α,12β,20S-Tetrahydroxydammar-24-ene 3-O-β-D-glucopyranoside (8) was prepared by deacetylation of 3
20
by NaOMe in MeOH (0.1 N) at 25°C (99% yield). Ñ Í Î , amorph., [α] +17.6° (c 0.8, Ñ Í N), R 0.20 (4), 0.44 (5).
36 62
9
D
5
5
f
1
Í NMR spectrum (700 MHz, C D N, δ, ppm, J/Hz): 0.897 (1H, td, J = 13.5, 3.5, H-1a), 0.939 (3Í, s, Ìå-19), 1.000 (3Í, s,
5
5
Ìå-30), 1.057 (1H, ddd, J = 12.1, 8.9, 1.8, H-15a), 1.088 (3Í, s, Ìå-18), 1.178 (1H, d, J = 10.4, H-5), 1.398 (1H, m, H-16a),
1.426 (3Í, s, Ìå-29), 1.428 (3Í, s, Ìå-21), 1.524 (1H, m, H-11a), 1.531 (1H, m, H-9), 1.557 (1H, m, H-1b), 1.602 (1H, m,
H-15b), 1.635 (3Í, s, Ìå-27), 1.665 (3Í, s, Ìå-26), 1.703 (1H, ddd, J = 13.5, 12.1, 5.4, H-22a), 1.883 (1H, m, H-7a), 1.889
(1H, m, H-16b), 2.087 (3Í, s, Ìå-28), 1.911 (1H, td, J = 13.5, 3.5, H-2a), 1.961 (1H, t, J = 11.6, H-7b), 2.037 (1H, t, J = 10.6,
H-13), 2.044 (1H, m, H-22b), 2.109 (1H, m, H-11b), 2.300 (1H, m, H-23a), 2.319 (1H, m, H-2b), 2.356 (1H, td, J = 10.8, 7.4,
H-17), 2.609 (1H, m, H-23b), 3.487 (1Í, dd, J = 11.9, 4.4, H-3α), 3.942 (1Í, td, J = 10.0, 5.7, Í-12α), 4.015 (1Í, ddd, J = 9.2,
5.6, 2.6, Í-5′), 4.089 (1H, t, J = 8.2, H-2′), 4.230 (1H, t, J = 8.9, H-4′), 4.264 (1H, t, J = 8.9, H-3′), 4.359 (1H, m, H-6β), 4.414
(1Í, dd, J = 11.7, 5.5, H-6b′), 4.599 (1Í, dd, J = 11.7, 2.6, H-6a′), 5.013 (1Í, d, J = 8.2, H-1′), 5.230 (1Í, d, J = 6.5, 6-ÎÍ),
13
5.328 (1Í, tt, J = 7.1, 1.4, Í-24), 6.241 (1Í, br.s, 6′-ÎÍ), 6.958 (1Í, br.s, 20-ÎÍ), 7.238 (1Í, br.s, 12-ÎÍ). C NMR
spectrum (176 MHz, C D N, δ, ppm): 17.13 (C-29), 17.20 (C-30), 17.54 (C-18), 17.58 (C-19), 17.80 (C-27), 23.12 (C-23),
5
5
25.93 (C-26), 26.73 (C-2), 26.97 (C-16), 27.19 (C-21), 31.47 (C-15), 31.59 (C-28), 32.16 (C-11), 35.98 (C-22), 38.98 (C-10),
39.21 (C-1), 40.68 (C-4), 41.24 (C-8), 47.64 (C-7), 48.39 (C-13), 50.14 (C-9), 51.76 (C-14), 54.90 (C-17), 61.95 (C-5), 63.28
(C-6′), 67.68 (C-6), 71.14 (C-12), 72.05 (C-4′), 73.10 (Ñ-20), 76.04 (C-2′), 78.47 (C-5′), 78.91 (C-3′), 89.59 (C-3), 107.36 (C-1′),
126.44 (C-24), 130.90 (C-25).
3β,6α,12β,20S-Tetrahydroxydammar-24-ene 12-O-β-D-glucopyranoside (9) was prepared by deacetylation
20
of 4 by NaOMe in MeOH (0.1 N) at 25°C (99% yield), amorph., [α] +2.4° (c 1.0, Ñ Í N), R 0.28 (4), 0.50 (5). Lit. [13]:
D
5
5
f
24
1
[α] +42.0° (c 0.15, MeOH). Í NMR spectrum (700 MHz, C D N, δ, ppm, J/Hz): 0.865 (3Í, s, Ìå-30), 0.895 (3Í, s,
D
5 5
Ìå-19), 0.926 (3Í, s, Ìå-18), 0.937 (1H, m, H-1a), 0.991 (1H, m, H-15a), 1.181 (1H, d, J = 10.5, H-5), 1.326 (3Í, s, Ìå-21),
1.355 (1H, m, H-16a), 1.384 (1H, m, H-11a), 1.426 (3Í, s, Ìå-29), 1.509 (1H, dd, J = 13.3, 3.1, H-9), 1.541 (1H, m, H-15b),
1.568 (1H, m, H-1b), 1.621 (1H, m, H-22a), 1.640 (3Í, s, Ìå-26), 1.646 (3Í, s, Ìå-27), 1.805 (1H, m, H-2a), 1.811 (1H, m,
85

H-16b), 1.831 (1H, m, H-7a), 1.868 (1H, m, H-2b), 1.884 (1H, m, H-7b), 1.948 (1H, m, H-22b), 1.978 (3Í, s, Ìå-28), 2.072
(1H, t, J = 10.6, H-13), 2.238 (1H, m, H-23a), 2.359 (1H, td, J = 10.6, 7.1, H-17), 2.366 (1H, m, H-11b), 2.581 (1H, m, H-23b),
3.516 (1Í, m, H-3α), 4.018 (1Í, ddd, J = 9.6, 5.0, 2.7, Í-5′), 4.092 (1H, dd, J = 9.1, 7.7, H-2′), 4.203 (1H, t, J = 9.2, H-4′),
4.295 (1H, t, J = 9.1, H-3′), 4.307 (1H, m, H-12α), 4.321 (1H, m, H-6b′), 4.342 (1H, m, H-6β), 4.475 (1Í, dd, J = 11.7, 2.7,
H-6a′), 5.195 (1Í, d, J = 6.7, 6-ÎÍ), 5.292 (1Í, d, J = 7.7, H-1′), 5.294 (1Í, br.s, 20-ÎÍ), 5.338 (1Í, tt, J = 7.2, 1.4, Í-24),
13
5.701 (1Í, d, J = 5.5, 3-ÎÍ). C NMR spectrum (176 MHz, C D N, δ, ppm): 16.45 (C-29), 17.24 (C-18), 17.33 (C-30), 17.44
5
5
(C-19), 17.69 (C-27), 22.94 (C-23), 25.80 (C-26), 26.82 (C-21), 27.13 (C-16), 27.85 (C-11), 28.10 (C-2), 31.26 (C-15), 31.93
(C-28), 36.44 (C-22), 38.99 (C-1), 39.38 (C-10), 40.32 (C-4), 41.02 (C-8), 46.34 (C-13), 47.23 (C-7), 49.80 (C-9), 52.08
(C-14), 54.10 (C-17), 61.71 (C-5), 62.59 (C-6′), 67.58 (C-6), 71.19 (C-4′), 73.00 (C-20), 75.31 (C-2′), 77.47 (Ñ-12), 78.35
(C-3), 78.39 (C-3′), 78.52 (C-5′), 100.37 (C-1′), 126.54 (C-24), 130.59 (C-25).
3β,6α,12β,20S-Tetrahydroxydammar-24-ene 20-O-β-D-glucopyranoside (10) was prepared by deacetylation of
20
5 by NaOMe in MeOH (0.1 N) at 25°C (99% yield). amorph., [α] +27.5° (c 0.8, Ñ Í N), R 0.25 (4), 0.47 (5). Lit. [14]:
D
5
5
f
25
1
[α] +36.6° (c 1.12, MeOH). Í NMR spectrum (700 MHz, C D N, δ, ppm, J/Hz): 0.977 (3Í, s, Ìå-30), 1.013 (1H, m,
D
5 5
H-15a), 1.017 (3Í, s, Ìå-19), 1.021 (1H, m, H-1a), 1.097 (3Í, s, Ìå-18), 1.223 (1H, d, J = 10.4, H-5), 1.351 (1H, m, H-16a),
1.454 (3Í, s, Ìå-29), 1.572 (1H, m, H-9), 1.556 (1H, m, H-11a), 1.600 (1H, m, H-15b), 1.602 (6Í, s, Ìå-26, 27), 1.624 (3Í,
s, Ìå-21), 1.724 (1H, dt, J = 12.7, 3.5, H-1b), 1.822 (1H, ddd, J = 14.1, 12.3, 5.2, H-22a), 1.836 (1H, m, H-16b), 1.868 (1H,
m, H-2a), 1.880 (1H, m, H-7a), 1.932 (1H, m, H-2b), 1.958 (1H, m, H-7b), 1.988 (3Í, s, Ìå-28), 1.997 (1H, t, J = 10.7, H-13),
2.105 (1H, m, H-11b), 2.250 (1H, m, H-23a), 2.399 (1H, ddd, J = 13.8, 12.3, 4.1, H-22b), 2.510 (1H, m, H-23b), 2.561 (1H, td,
J = 10.4, 8.5, H-17), 3.522 (1Í, dd, J = 11.7, 4.9, H-3α), 3.931 (1Í, ddd, J = 9.6, 5.5, 2.7, Í-5′), 4.008 (1H, dd, J = 9.0, 7.8, H-2′),
4.170 (1H, t, J = 9.1, H-4′), 4.187 (1H, m, H-12α), 4.237 (1H, t, J = 9.1, H-3′), 4.327 (1Í, dd, J = 11.7, 5.5, H-6b′), 4.409 (1H,
m, H-6β), 4.495 (1Í, dd, J = 11.7, 2.7, H-6a′), 5.191 (1Í, d, J = 7.7, H-1′), 5.259 (1Í, m, Í-24), 5.576 (1Í, s, 12-ÎÍ).
13
C NMR spectrum (176 MHz, C D N, δ, ppm): 16.50 (C-29), 17.41 (C-30), 17.45 (C-19), 17.59 (C-18), 17.74 (C-27), 22.33
5
5
(C-21), 23.19 (C-23), 25.74 (C-26), 26.63 (C-16), 28.13 (C-2), 30.77 (C-15), 30.93 (C-11), 31.98 (C-28), 36.13 (C-22), 39.35
(C-10), 39.38 (C-1), 40.33 (C-4), 41.20 (C-8), 47.49 (C-7), 49.15 (C-13), 49.90 (C-9), 51.35 (C-14), 51.60 (C-17), 61.75
(C-5), 62.91 (C-6′), 67.72 (C-6), 70.17 (Ñ-12), 71.68 (C-4′), 75.14 (C-2′), 78.26 (C-5′), 78.47 (C-3), 79.32 (C-3′), 83.26
(C-20), 98.25 (C-1′), 125.96 (C-24), 130.92 (C-25).
3β,6α,12β,20S-Tetrahydroxydammar-24-ene 3,12-di-O-β-D-glucopyranoside (11) was prepared by deacetylation
20
of 6 by NaOMe in MeOH (0.1 N) at 25°C (98% yield). Ñ Í Î , amorph., [α] –6.5° (c 0.8, Ñ Í N), R 0.08 (4), 0.20 (5).
42 72 14
D
5
5
f
1
Í NMR spectrum (700 MHz, C D N, δ, ppm, J/Hz): 0.757 (1H, td, J = 13.6, 3.8, H-1à), 0.808 (3Í, s, Ìå-19), 0.877 (3Í, s,
5
5
Ìå-18), 0.883 (3Í, s, Ìå-30), 0.968 (1H, ddd, J = 12.2, 8.8, 2.1, H-15à), 1.122 (1H, d, J = 10.4, H-5), 1.325 (3Í, s, Ìå-21),
1.349 (1H, m, H-16à), 1.385 (3Í, s, Me-29), 1.410 (1H, dd, J = 13.7, 3.8, H-1b), 1.430 (1H, m, H-11à), 1.433 (1H, m, H-9),
1.518 (1H, m, H-15b), 1.598 (1H, ddd, J = 13.3, 11.8, 5.4, H-22à), 1.624 (3Í, s, Me-26), 1.631 (3Í, s, Ìå-27), 1.797 (1H, m,
H-16b), 1.804 (1H, dd, J = 12.3, 3.8, H-7à), 1.830 (1H, m, H-2à), 1.870 (1H, t, J = 12.3, H-7b), 1.926 (1H, ddd, J = 13.4, 11.9,
4.5, H-22b), 2.040 (1H, t, J = 10.8, H-13), 2.056 (3Í, s, Ìå-28), 2.212 (1H, m, H-23à), 2.247 (1H, m, H-2b), 2.290 (1H, ddd,
J = 13.0, 5.3, 2.8, H-11b), 2.559 (1H, m, H-23b), 2.376 (1H, td, J = 10.6, 7.1, H-17), 3.443 (1Í, dd, J = 12.1, 4.6, H-3α), 4.026
(1Í, ddd, J = 9.2, 5.4, 2.5, Í-5′), 4.063 (1Í, ddd, J = 9.4, 5.2, 2.5, Í-5′′), 4.083 (1H, t, J = 9.1, H-2′′), 4.085 (1H, t, J = 9.1,
H-2′), 4.222 (1H, t, J = 9.1, H-4′), 4.226 (1H, t, J = 9.1, H-4′′), 4.263 (1H, t, J = 9.1, H-3′), 4.279 (1H, m, H-6β), 4.296 (1H, m,
H-12α), 4.329 (1H, t, J = 9.1, H-3′′), 4.333 (1Í, dd, J = 12.0, 5.2, H-6b′′), 4.447 (1Í, dd, J = 11.7, 5.4, H-6b′), 4.505 (1Í, dd,
J = 12.0, 2.5, H-6a′′), 4.635 (1Í, dd, J = 11.7, 2.5, H-6a′), 5.001 (1Í, d, J = 7.7, H-1′), 5.268 (1Í, d, J = 7.7, H-1′′), 5.310 (1H,
13
tt, J = 7.1, 1.4, H-24). C NMR spectrum (176 MHz, C D N, δ, ppm): 16.91 (C-29), 17.17 (C-18), 17.29 (C-19), 17.32
5
5
(C-30), 17.64 (C-27), 22.88 (C-23), 25.75 (C-26), 26.55 (C-2), 26.66 (C-21), 27.05 (C-16), 27.85 (C-11), 31.19 (C-15), 31.37
(C-28), 36.34 (C-22), 38.68 (C-1), 38.85 (C-10), 40.47 (C-4), 40.91 (C-8), 46.30 (C-13), 47.14 (C-7), 49.67 (C-9), 52.05
(C-14), 54.04 (C-17), 61.72 (C-5), 62.50 (C-6′′), 63.10 (C-6′), 67.39 (C-6), 71.16 (C-4′′), 71.83 (C-4′), 73.06 (C-20), 75.26
(C-2′′), 75.85 (C-2′), 77.61 (Ñ-12), 78.31 (C-5′), 78.45 (C-3′′), 78.67 (C-5′′), 78.71 (C-3′), 89.42 (C-3), 100.51 (C-1′′), 107.19
(C-1′), 126.42 (C-24), 130.61 (C-25).
3β,6α,12β,20S-Tetrahydroxydammar-24-ene 3,20-di-O-β-D-glucopyranoside (12) was prepared by deacetylation
20
of 7 by NaOMe in MeOH (0.1 N) at 25°C (98% yield). amorph., [α] +20.1° (c 0.75, Ñ Í N), R 0.06 (4), 0.16 (5). Lit. [15]:
D
5
5
f
1
mp 190–191°Ñ. Í NMR spectrum (700 MHz, C D N, δ, ppm, J/Hz): 0.886 (1H, m, H-1à), 0.946 (3Í, s, Ìå-19), 1.004 (3Í,
5
5
s, Ìå-30), 1.010 (1H, m, H-15à), 1.066 (3Í, s, Ìå-18), 1.168 (1H, d, J = 10.6, H-5), 1.344 (1H, m, H-16à), 1.423 (3Í, s,
Ìå-29), 1.502 (1H, m, H-9), 1.503 (1H, m, H-11à), 1.585 (1H, m, H-15b), 1.595 (3Í, s, Me-27), 1.600 (3Í, s, Me-26), 1.600
(1H, m, H-1b), 1.623 (3Í, s, Ìå-21), 1.811 (1H, ddd, J = 13.9, 12.3, 5.1, H-22à), 1.846 (1H, m, H-16b), 1.855 (1H, dd, J = 12.3,
86

3.8, H-7à), 1.907 (1H, dd, J = 12.3, 3.7, H-2à), 1.955 (1H, t, J = 12.3, H-7b), 1.978 (1H, t, J = 10.6, H-13), 2.039 (1H, dd,
J = 10.6, 5.1, H-11b), 2.067 (3Í, s, Ìå-28), 2.239 (1H, m, H-23à), 2.328 (1H, dd, J = 13.6, 4.4, H-2b), 2.390 (1H, ddd, J = 13.9,
12.3, 4.1, H-22b), 2.504 (1H, m, H-23b), 2.566 (1H, td, J = 10.6, 8.6, H-17), 3.468 (1Í, dd, J = 11.9, 4.6, H-3α), 3.931 (1Í, ddd,
J = 9.6, 5.4, 2.7, Í-5′′), 4.007 (2H, m, H-5′, 2′′), 4.087 (1H, dd, J = 8.9, 7.7, H-2′), 4.161 (1H, t, J = 9.1, H-4′′), 4.179 (1H, m,
H-12α), 4.221 (1H, t, J = 9.1, H-4′), 4.234 (1H, t, J = 9.0, H-3′′), 4.257 (1H, t, J = 8.9, H-3′), 4.322 (1Í, dd, J = 11.7, 5.5,
H-6b′′), 4.349 (1H, td, J = 10.5, 3.8, H-6β), 4.406 (1Í, dd, J = 11.7, 5.6, H-6b′), 4.492 (1Í, dd, J = 11.7, 2.7, H-6a′′), 4.604 (1Í,
13
dd, J = 11.7, 2.6, H-6a′), 5.001 (1Í, d, J = 7.7, H-1′), 5.193 (1Í, d, J = 7.7, H-1′′), 5.249 (1H, tt, J = 7.2, 1.4, H-24). C NMR
spectrum (176 MHz, C D N, δ, ppm): 17.00 (C-29), 17.37 (C-19), 17.43 (C-30), 17.57 (C-18), 17.74 (C-27), 22.34 (C-21), 23.19
5
5
(C-23), 25.74 (C-26), 26.64 (C-2), 26.64 (C-16), 30.76 (C-15), 30.91 (C-11), 31.43 (C-28), 36.13 (C-22), 38.87 (C-10), 39.15
(C-1), 40.54 (C-4), 41.14 (C-8), 47.50 (C-7), 49.17 (C-13), 49.82 (C-9), 51.35 (C-14), 51.58 (C-17), 61.80 (C-5), 62.94 (C-6′′),
63.17 (C-6′), 67.56 (C-6), 70.15 (Ñ-12), 71.71 (C-4′′), 71.95 (C-4′), 75.14 (C-2′′), 75.91 (C-2′), 78.27 (C-5′′), 78.33 (C-5′), 78.79
(C-3′), 79.32 (C-3′′), 83.26 (C-20), 89.47 (C-3), 98.27 (C-1′′), 107.23 (C-1′), 125.95 (C-24), 130.91 (C-25).
ACKNOWLEDGMENT
We thank the Korea Ginseng & Tobacco Research Institute (now Korean Ginseng Corp., Central Research Institute,
Daejeon, Korea) for supplying 20S-protopanaxatriol.
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