Synthesis of 3α,20S-Dihydroxydammar-24-en-12-One β-D-Glucopyranosides

Article abstract of DOI:10.1007/s10600-020-03174-0

3α,20S-Dihydroxydammar-24-en-12-one 3-, 20-, and 3,20-di-O-β-D-glucopyranosides, close structural analogs of chikusetsusaponin-LT₈ glycoside from Panax japonicus, were synthesized for the first time. Condensation of 3,20S-dihydroxydammar-24-en-12-one (1) with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (6) in the presence of Ag₂O gave a mixture of the three acetylated 3-, 20-, and 3,20-di-O-β-Dglucopyranosides 7–9 with 7 dominating (34.6%). Glycosylation of 3α-acetoxy-20S-hydroxydammar-24-en-12-one by glycosyl donor 6 led to regio- and stereoselective formation of acetylated 20-O-β-Dglucopyranoside 10 (48.6%). Subsequent removal of the protecting groups by sodium methoxide gave the corresponding free 3-, 20-, and 3,20-di-O-β-D-glucopyranosides 11–13.

Full text of DOI:10.1007/s10600-020-03174-0

DOI 10.1007/s10600-020-03174-0
Chemistry of Natural Compounds, Vol. 56, No. 5, September, 2020
SYNTHESIS OF 3α,20S-DIHYDROXYDAMMAR-24-EN-12-ONE
β-D-GLUCOPYRANOSIDES
L. N. Atopkina* and V. A. Denisenko
3α,20S-Dihydroxydammar-24-en-12-one 3-, 20-, and 3,20-di-O-β-D-glucopyranosides, close structural
analogs of chikusetsusaponin-LT glycoside from Panax japonicus, were synthesized for the first time.
8
Condensation of 3,20S-dihydroxydammar-24-en-12-one (1) with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl
bromide (6) in the presence of Ag O gave a mixture of the three acetylated 3-, 20-, and 3,20-di-O-β-D-
2
glucopyranosides 7–9 with 7 dominating (34.6%). Glycosylation of 3α-acetoxy-20S-hydroxydammar-24-
en-12-one by glycosyl donor 6 led to regio- and stereoselective formation of acetylated 20-O-β-D-
glucopyranoside 10 (48.6%). Subsequent removal of the protecting groups by sodium methoxide gave the
corresponding free 3-, 20-, and 3,20-di-O-β-D-glucopyranosides 11–13.
Keywords: dammarane-type triterpenoids, 3α,20S-dihydroxydammar-24-en-12-one, glycosylation.
Chemical modification of known compounds to reveal the structural elements affecting their activity is one possible
pathway to the discovery of biologically active compounds. Carbonyl groups are some of the most important pharmacophores
in steroidal and triterpenoid glycosides and affect their cytotoxicity and hemolytic and other types of biological activity
[1–10]. Dammarane triterpenoid glycosides, the molecules of which contain a carbonyl, were isolated from leaves and fruit of
Panax japonicus C. A. Meyer [11, 12] and were also detected among the biotransformation products of P. ginseng glycosides
and their aglycons through the action of various microorganisms, fungi, and enzymes [5–9]. It seemed worthwhile to expand
the library of dammarane triterpenoids and their glycosides because the presence of a carbonyl in them not only strengthens
their cytotoxicity against tumor cells [3–6] but also weakens their hemolytic effect [10]. Herein, studies of the synthesis of
glycosides based on dammarane-type tetracyclic triterpenoids, in particular, of β-D-glucopyranosides of
3α,20S-dihydroxydammar-24-en-12-one, close structural analogs of chikusetsusaponin-LT , a glycoside from P. japonicus
8
C. A. Meyer, are reported.
3α,20S-Dihydroxydammar-24-en-12-one (1) differs from the 12-keto derivative of 20S-protopanaxadiol
(3β,20S-dihydroxydammar-24-en-12-one), the aglycon of natural dammarane-type glycosides (chikustesusaponins-LT , -LT ,
8
5
-LN ) [11], only by the configuration of the C-3 hydroxyl. The starting compound for preparing ketone 1 was betulafolientriol
4
(3α,12β,20S-trihydroxydammar-24-ene, 2), one of the constituents in the extract of Betula birch leaves [13]. Oxidation of 2
by CrO in Py gave the 3-ketone of betulafolientriol (3α,20S-dihydroxydammar-24-en-3-one) as the major reaction product
3
(70%). The 12-ketone (1) was a minor product (6%). Therefore, the 12-OH of betulafolientriol was oxidized with preliminary
protective acetylation of the 3-OH group. The 3-O-acetyl derivative of 3 was prepared via partial deacetylation of betulafolientriol
diacetate (4) by NaOMe in MeOH (87%) [14]. Oxidation of 3 monoacetate by CrO in Py gave 3α-acetoxy-20S-hydroxydammar-
3
24-en-12-one (5) (75%) [15]. The 12-ketone of 1 was obtained in quantitative yield after removal of the acetyl protection in 5.
Condensation of 1 with an equimolar amount of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (6) in the presence
of Ag O in CH Cl –CH NO (1:1) gave acetylated 3-, 20-, and 3,20-di-O-β-D-glucopyranosides 7–9 in yields of 34.6, 17.3,
2
2
2
3
2
and 7.4%, respectively. Tertiary C-20-OH was glycosylated using ketone 5, reaction of which with a two-fold excess of 6 in
the presence of Ag O in CH Cl gave regio- and stereoselectively 20-O-β-D-glucopyranoside 10 (48.6%). Deacetylation of
2
2
2
7–9 by NaOMe (0.1 N) in MeOH at 25°C gave the corresponding free β-D-glucopyranosides 11–13 in quantitative yields.
Two of them, 20- and 3,20-di-O-β-D-glucopyranosides 12 and 13, were 3-epimers of chikusetsusaponin-LT and its prosapogenin [11].
8
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. 5, September–October, 2020, pp. 751–755. Original article submitted January 20, 2020.
©
878
0009-3130/20/5605-0878 2020 Springer Science+Business Media, LLC

21
HO
R O
24
24
R O
2
26
2
12
O
20
20
17
12
13
27
19
5
18
1
9
3
3
30
R O
1
R O
1
29
28
1, 5, 7 - 13
2 - 4
1: R = R = H; 2: R = R = H; 3: R = Ac, R = H; 4: R = R = Ac
1
2
1
2
1
2
1
2
5: R = Ac, R = H; 7: R = β-D-GlcAc , R = H; 8: R = H, R = β-D-GlcAc
1
2
1
4
2
1
2
4
9: R = R = β-D-GlcAc ; 10: R = Ac, R = β-D-GlcAc ; 11: R = β-D-Glc, R = H
1
2
4
1
2
4
1
2
12: R = H, R = β-D-Glc; 13: R = R = β-D-Glc
1
2
1
2
13
The structures of all compounds were elucidated by IR, PMR, C NMR, and 2D spectroscopy (COSY, NOESY,
HSQC, HMBC, HSQC-TOCSY). Doublets for the anomeric protons of the glucose residues of acetylated glucosides 7–10
appeared in PMR spectra in CDCl at δ 4.490–4.493 ppm for C-3 and 4.610–4.611 ppm for C-20; of free glucosides 11–13 in
3
PMR spectra in Py at δ 4.827 ppm for C-3 and 5.077–5.089 ppm for C-20. Chemical shifts and spin–spin coupling constants
of anomeric glucose protons (J
synthesized glycosides. The site of attachment of the glucose residues was confirmed by comparing C NMR spectra of 1, 5,
and 7–13.
= 7.6–7.8 Hz) were indicative of the trans-configuration of the glycoside bond in all
1′,2′
13
EXPERIMENTAL
13
PMR and C NMR spectra of 1, 5, and 7–10 were recorded in CDCl ; of 11–13, in C D N on a Bruker Avance-500
3
5 5
1
13
spectrometer at operating frequency 500 MHz for H and 125 MHz for C at 30°C and a Bruker Avance-700 spectrometer
at operating frequency 700 and 176 MHz, respectively. Chemical shifts were given on the δ-scale vs. TMS. Multiplicities of
13
1
1
C resonances were found from DEPT-135 experiments using the standard method. Homonuclear H– H 2D COSY-45 and
1
13
NOESY spectra and heteronuclear H– C 2D HSQC and HMBC spectra were also taken using standard methods. HMBC
experiments were optimized for J
n
≈ 5 Hz. IR spectra were recorded in CHCl solution on a Bruker Vector 22
HC
3
spectrophotometer. High-resolution mass spectra (HR-MS) were recorded on a Bruker Maxis Impact II instrument. Optical
rotation was determined on a PerkinElmer 343 polarimeter in a 10-cm cuvette at 20°C. Melting points were measured on
a Boetius apparatus. Column chromatography used KSK silica gel (120–150 mesh) and solvent systems hexane–Me CO
2
(20:1→6:1). The purity of compounds was monitored by TLC on Silica Gel 60 F
plates (Merck) using solvent systems
254
hexane–Me CO (2:1 and 3:2) and C H –CHCl –MeOH (6:4:1, 3:2:1, 2:1:1). Detection was made by H SO (10%) in EtOH
2
6
6
3
2
4
with heating at 100–200°C. Elemental analyses of all newly synthesized compounds agreed with those calculated.
Betulafolientriol (2) was isolated from the unsaponified part of the Et O extract of Betula pendula leaves followed by
2
chromatography over a column of silica gel and crystallization from Me CO, mp 195–196°C, lit. [13] mp 197–198°C.
2
3α,12β-Diacetoxy-20S-hydroxydammar-24-ene (4) was prepared via acetylation of triol 2 by acetic anhydride in
Py at 25°C for 1 d as before [14].
3α-Acetoxy-12β,20S-dihydroxydammar-24-ene (3) was prepared via partial deacetylation of diacetate 4 by NaOMe
(0.1 N) in MeOH at 25°C for 4–5 h (TLC monitoring) as before [14], mp 216–218°C (Me CO) [15].
2
3α-Acetoxy-20S-hydroxydammar-24-en-12-one (5) was prepared as before [15], mp 218–220°C (EtOH) [15].
1
Í NMR spectrum (700 MHz, CDCl , δ, ppm, J/Hz): 0.848 (3H, s, Me-30), 0.860 (3H, s, Me-28), 0.917 (3H, s, Me-29), 0.956
3
(3H, s, Me-19), 1.116 (3H, s, Me-21), 1.192 (3H, s, Me-18), 1.618 (3H, s, Me-27), 1.685 (3H, s, Me-26), 2.072 (3H, s, CH CO),
3
2.214 (1H, t, J = 14.0, H-11a), 2.294 (1H, dd, J = 14.3, 4.1, H-11b), 2.415 (1H, td, J = 10.5, 6.8, H-17), 2.871 (1H, d, J = 10.5,
13
H-13), 4.645 (1H, t, J = 3.0, H-3β), 5.105 (1H, tt, J = 7.2, 1.4, H-24). C NMR spectrum (176 MHz, CDCl , δ, ppm): 15.66
3
(C-19), 15.98 (C-18), 17.61 (C-30), 17.67 (C-27), 18.10 (C-6), 21.31 (CH CO), 21.60 (C-29), 22.46 (C-23), 22.66 (C-2),
3
24.65 (C-16), 25.71 (C-26), 26.37 (C-21), 27.86 (C-28), 30.84 (C-15), 33.75 (C-1), 33.86 (C-7), 36.70 (C-4), 37.53 (C-10),
37.91 (C-22), 39.07 (C-11), 40.41 (C-8), 45.99 (C-17), 50.63 (C-5), 53.23 (C-9), 54.91 (C-14), 56.16 (C-13), 73.14 (C-20),
77.87 (C-3), 124.88 (C-24), 131.48 (C-25), 170.65 (CH CO), 213.99 (C-12).
3
879

3α,20S-Dihydroxydammar-24-en-12-one (1) was prepared via deacetylation of 5 by KOH solution (10%) in MeOH.
20
–1
C H O , mp 193–195°Ñ (Me CO); [α] +37.2° (c 0.7, CHCl ). IR spectrum (ν, cm ): 1690 (Ñ=Î), 3416 (ÎÍ), 3608
30 50
1
3
2
D
3
(ÎÍ). Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.815 (3H, s, Me-30), 0.868 (3H, s, Me-29), 0.941 (3H, s, Me-19),
3
0.960 (3H, s, Me-28), 1.115 (3H, s, Me-21), 1.177 (3H, s, Me-18), 1.616 (3H, s, Me-27), 1.683 (3H, s, Me-26), 2.197 (1H, t,
J = 14.4, H-11a), 2.315 (1H, dd, J = 14.3, 4.4, H-11b), 2.403 (1H, td, J = 10.4, 7.0, H-17), 2.848 (1H, d, J = 10.4, H-13), 3.415
13
(1H, t, J = 2.9, H-3β), 5.102 (1H, tt, J = 7.1, 1.4, H-24). C NMR spectrum (125 MHz, CDCl , δ, ppm): 15.65 (C-19), 15.97
3
(C-18), 17.61 (C-30), 17.67 (C-27), 18.24 (C-6), 21.98 (C-29), 22.44 (C-23), 24.71 (C-16), 25.26 (C-2), 25.71 (C-26), 26.42
(C-21), 28.32 (C-28), 30.68 (C-15), 33.09 (C-1), 33.90 (C-7), 37.54 (C-4), 37.61 (C-10), 37.73 (C-22), 39.03 (C-11), 40.39
(C-8), 46.19 (C-17), 49.27 (C-5), 53.10 (C-9), 54.79 (C-14), 56.17 (C-13), 73.06 (C-20), 75.88 (C-3), 124.94 (C-24), 131.43
–
(C-25), 211.20 (C-12). HR-ESI-MS m/z 457.3691 [M – H] (calcd for C H O , 457.3687).
30 49
3
Condensation of Ketones 1 and 5 with 2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosyl Bromide (6) in the Presence
of Ag O. 1) A mixture of 1 (138 mg, 0.30 mmol), Ag O (70 mg, 0.30 mmol), and α-acetobromoglucose (6, 123 mg,
2
2
0.30 mmol) in CH Cl –CH NO (1:1, 5 mL) was stirred continuously at 20°C for 5 h until 6 disappeared (TLC monitoring),
2
2
3
2
diluted with CHCl , and filtered to remove insoluble Ag compounds. The solvent was distilled off at reduced pressure.
3
The residue was worked up (3×) with hot H O to remove water-soluble glucose derivatives and dried. The dry residue was
2
chromatographed over a column of silica gel with elution by hexane–Me CO (10:1→6:1) to afford ketone 1 (55 mg, 39.8%),
2
3-monoglucoside 7 (82 mg, 34.6%), 20-monoglucoside 8 (41 mg, 17.3%), and 3,20-diglucoside 9 (25 mg, 7.4%).
2) A mixture of ketone 5 (418 mg, 0.83 mmol), Ag O (195 mg, 0.83 mmol), α-acetobromoglucose (6, 343 mg,
2
°
0.83 mmol), and 4-A molecular sieves (0.7 g) in CH Cl (7 mL) was stirred continuously at 20°C for 4 h, treated with more
2
2
Ag O (200 mg, 0.83 mmol) and α-acetobromoglucose (6, 343 mg, 0.83 mmol), and stirred for another 4 h until 6 disappeared
2
(TLC monitoring). The reaction mixture was worked up as in the preceding experiment. The dry residue was chromatographed
over a column of silica gel with elution by hexane–Me CO (20:1→10:1) to afford ketone 5 (208 mg, 49.8%) and
2
20-O-glucoside 10 (337 mg, 48.6%).
20S-Hydroxy-3α-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)dammar-24-en-12-one (7). C H O ,
44 68 12
20
–1
mp 179–180°C (hexane–Me CO), [α] +2.0° (c 0.8, CHCl ). IR spectrum (ν, cm ): 1704 (Ñ=Î), 1755 (ÑÍ Ñ=Î), 3420
(ÎÍ). Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.810 (3H, s, Me-30), 0.856 (3H, s, Me-29), 0.920 (3H, s, Me-28),
2
D
3
3
1
3
0.929 (3H, s, Me-19), 1.106 (3H, s, Me-21), 1.161 (3H, s, Me-18), 1.611 (3H, s, Me-27), 1.681 (3H, s, Me-26), 1.997,
1.997, 2.022, 2.068 (3H each, s, CH CO), 2.206 (2Í, d, J = 8.7, H-11), 2.393 (1H, td, J = 10.4, 6.8, H-17), 2.851 (1H, d,
3
J = 10.4, H-13), 3.354 (1H, t, J = 2.8, H-3β), 3.631 (1Í, ddd, J = 9.9, 4.8, 2.8, Í-5′), 4.153 (1Í, dd, J = 12.1, 2.9, Í-6a′),
4.222 (1Í, dd, J = 12.1, 4.9, Í-6b′), 4.490 (1Í, d, J
Í-4′), 5.098 (1H, tt, J = 7.2, 1.4, H-24), 5.205 (1Í, t, J = 9.5, Í-3′). C NMR spectrum (125 MHz, CDCl , δ, ppm): 15.89
= 7.8, Í-1′), 4.982 (1Í, dd, J = 9.7, 8.0, Í-2′), 5.067 (1Í, t, J = 9.7,
1′,2′
13
3
(C-18), 15.90 (C-19), 17.42 (C-30), 17.66 (C-27), 17.96 (C-6), 20.68 (C-2), 20.60, 20.60, 20.69, 20.82 (4CH CO), 21.90
3
(C-29), 22.46 (C-23), 24.61 (C-16), 25.71 (C-26), 26.38 (C-21), 28.55 (C-28), 30.80 (C-15), 33.27 (C-1), 33.88 (C-7),
37.03 (C-4), 37.24 (C-10), 37.90 (C-22), 39.13 (C-11), 40.43 (C-8), 45.98 (C-17), 49.61 (C-5), 53.34 (C-9), 54.88 (C-14),
56.19 (C-13), 62.11 (C-6′), 68.96 (C-4′), 71.45 (C-5′), 71.50 (C-2′), 72.88 (C-3′), 73.15 (C-20), 81.41 (C-3), 97.69 (C-1′),
124.88 (C-24), 131.48 (C-25), 169.00, 169.46, 170.27, 170.58 (4CH CO), 214.07 (C-12). HR-ESI-MS m/z 787.4643
3
–
[M – H] (calcd for C H O , 787.4638).
44 67 12
3α-Hydroxy-20S-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)dammar-24-en-12-one (8). C H O ,
44 68 12
20
–1
mp 207–209°C (EtOH); [α] +26.8° (c 0.25, CHCl ). IR spectrum (ν, cm ): 1704 (Ñ=Î), 1755 (ÑÍ Ñ=Î), 3600 (ÎÍ).
Í NMR spectrum (500 MHz, CDCl , δ, ppm, J/Hz): 0.745 (3H, s, Me-30), 0.865 (3H, s, Me-29), 0.952 (6H, s, Me-19, 28),
D
3
3
1
3
1.037 (3H, s, Me-21), 1.202 (3H, s, Me-18), 1.608 (3H, s, Me-27), 1.656 (3H, s, Me-26), 1.982, 1.982, 2.022, 2.051 (3H each,
s, CH CO), 2.143 (1H, t, J = 12.7, H-11a), 2.192 (1H, dd, J = 12.7, 4.4, H-11b), 2.464 (1H, td, J = 10.0, 5.1, H-17), 3.007 (1H,
3
d, J = 9.7, H-13), 3.407 (1H, t, J = 2.8, H-3β), 3.661 (1Í, ddd, J = 10.0, 6.7, 2.4, Í-5′), 4.086 (1Í, dd, J = 12.0, 2.4, Í-6a′),
4.151 (1Í, dd, J = 12.0, 6.8, Í-6b′), 4.610 (1Í, d, J
Í-4′), 5.044 (1H, tt, J = 7.0, 1.4, H-24), 5.181 (1Í, t, J = 9.5, Í-3′). C NMR spectrum (125 MHz, CDCl , δ, ppm): 15.62
= 7.8, Í-1′), 4.937 (1Í, dd, J = 9.5, 7.8, Í-2′), 4.982 (1Í, t, J = 9.7,
1′,2′
13
3
(C-18), 15.96 (C-19), 16.88 (C-30), 17.67 (C-27), 18.29 (C-6), 20.59, 20.61, 20.62, 20.82 (4CH CO), 21.97 (C-29), 23.31
3
(C-21), 23.53 (C-16), 23.72 (C-23), 25.27 (C-2), 25.66 (C-26), 28.31 (C-28), 31.61 (C-15), 33.30 (C-1), 34.37 (C-7), 37.59
(C-4), 37.80 (C-10), 38.84 (C-22), 39.66 (C-11), 40.72 (C-8), 41.03 (C-17), 49.40 (C-5), 54.37 (C-9), 55.49 (C-13), 56.37
(C-14), 62.66 (C-6′), 68.98 (C-4′), 71.56 (C-5′), 71.96 (C-2′), 73.26 (C-3′), 75.99 (C-3), 82.24 (C-20), 94.60 (C-1′), 124.31
–
(C-24), 131.62 (C-25), 169.06, 169.56, 170.22, 170.63 (4CH CO), 211.97 (C-12). HR-ESI-MS m/z 787.4640 [M – H]
3
(calcd for C H O , 787.4638).
44 67 12
880

3α,20S-Di-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)dammar-24-en-12-one (9). C H O
,
58 86 21
20
–1
1
mp 145–148°C (EtOH), [α] –6.0° (c 0.4, CHCl ). IR spectrum (ν, cm ): 1704 (Ñ=Î), 1755 (ÑÍ Ñ=Î). Í NMR spectrum
D
3
3
(500 MHz, CDCl , δ, ppm, J/Hz): 0.747 (3H, s, Me-30), 0.852 (3H, s, Me-29), 0.912 (3H, s, Me-28), 0.941 (3H, s, Me-19),
3
1.025 (3H, s, Me-21), 1.191 (3H, s, Me-18), 1.600 (3H, s, Me-27), 1.652 (3H, s, Me-26), 1.972, 1.980, 1.995, 2.013, 2.019,
2.019, 2.050, 2.067 (3H each, s, CH CO), 2.087 (1H, m, H-11a), 2.170 (1H, t, J = 13.0, H-11b), 2.450 (1H, td, J = 9.9, 5.3,
3
H-17), 3.014 (1H, d, J = 9.7, H-13), 3.352 (1H, br.s, H-3β), 3.642 (2Í, m, Í-5′, 5′′), 4.085 (1Í, dd, J = 12.0, 2.3, Í-6a′′), 4.149
(1Í, dd, J = 12.0, 6.5, Í-6b′′), 4.152 (1Í, dd, J = 12.0, 3.0, Í-6a′), 4.219 (1Í, dd, J = 12.1, 4.9, Í-6b′), 4.493 (1Í, d,
J
= 7.8, Í-1′), 4.600 (1Í, d, J
= 7.8, Í-1′′), 4.935 (1Í, dd, J = 9.5, 8.0, Í-2′′), 4.979 (1Í, t, J = 9.7, Í-4′′), 4.982 (1Í,
1′,2′
1′′, 2′′
dd, J = 9.7, 8.0, Í-2′), 5.039 (1H, m, H-24), 5.064 (1Í, t, J = 9.7, Í-4′), 5.178 (1Í, t, J = 9.5, Í-3′′), 5.203 (1Í, t, J = 9.5,
13
Í-3′). C NMR spectrum (125 MHz, CDCl , δ, ppm): 15.56 (C-18), 16.24 (C-19), 16.78 (C-30), 17.66 (C-27), 18.01 (C-6),
3
20.62 (C-2), 20.58, 20.61, 20.61, 20.61, 20.61, 20.70, 20.80, 20.82 (8CH CO), 21.87 (C-29), 23.34 (C-21), 23.45 (C-16),
3
23.72 (C-23), 25.65 (C-26), 28.52 (C-28), 31.68 (C-15), 33.47 (C-1), 34.39 (C-7), 37.06 (C-4), 37.41 (C-10), 38.83 (C-22),
39.77 (C-11), 40.80 (C-8), 41.04 (C-17), 49.68 (C-5), 54.67 (C-9), 55.54 (C-13), 56.51 (C-14), 62.11 (C-6′), 62.64 (C-6′′),
68.97 (C-4′), 68.98 (C-4′′), 71.43 (C-5′), 71.50 (C-2′), 71.55 (C-5′′), 71.96 (C-2′′), 72.89 (C-3′), 73.23 (C-3′′), 81.26 (C-3),
82.15 (C-20), 94.59 (C-1′′), 97.51 (C-1′), 124.26 (C-24), 131.65 (C-25), 168.99, 169.04, 169.45, 169.54, 170.22, 170.31,
–
170.61, 170.62 (8CH CO), 212.16 (C-12). HR-ESI-MS m/z 1117.5584 [M – H] (calcd for C H O , 1117.5589).
3
58 85 21
3α-Acetoxy-20S-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)dammar-24-en-12-one (10). C H O ,
46 70 13
20
–1
mp 178–181°C (EtOH), [α] +4.0° (c 1.0, CHCl ). IR spectrum (ν, cm ): 1704 (Ñ=Î), 1730 (ÑÍ Ñ=Î), 1755 (ÑÍ Ñ=Î).
D
3
3
3
1
Í NMR spectrum (700 MHz, CDCl , δ, ppm, J/Hz): 0.775 (3H, s, Me-30), 0.852 (3H, s, Me-28), 0.913 (3H, s, Me-29), 0.966
3
(3H, s, Me-19), 1.037 (3H, s, Me-21), 1.216 (3H, s, Me-18), 1.615 (3H, s, Me-27), 1.659 (3H, s, Me-26), 1.983, 1.983, 2.023,
2.054, 2.070 (3H each, s, CH CO), 2.167 (2H, m, Í-11), 2.472 (1H, td, J = 10.4, 5.3, H-17), 3.031 (1H, d, J = 9.6, H-13), 3.663
3
(1Í, ddd, J = 10.1, 6.8, 2.4, Í-5′), 4.086 (1Í, dd, J = 12.0, 2.4, Í-6a′), 4.157 (1Í, dd, J = 12.0, 6.8, Í-6b′), 4.611 (1Í, d,
J
= 7.8, Í-1′), 4.633 (1H, t, J = 2.8, H-3β), 4.940 (1Í, dd, J = 9.4, 7.8, Í-2′), 4.985 (1Í, t, J = 9.7, Í-4′), 5.050 (1H, tt, J = 7.2, 1.4,
1′,2′
13
H-24), 5.184 (1Í, t, J = 9.5, Í-3′). C NMR spectrum (176 MHz, CDCl , δ, ppm): 15.64 (C-18), 15.97 (C-19), 16.94 (C-30), 17.68
3
(C-27), 18.16 (C-6), 20.58 (CH CO), 20.61 (CH CO), 20.62 (CH CO), 20.83 (CH CO), 21.34 (CH CO), 21.61 (C-29), 22.71
3
3
3
3
3
(C-2), 23.35 (C-21), 23.52 (C-16), 23.76 (C-23), 25.67 (C-26), 27.87 (C-28), 31.73 (C-15), 33.95 (C-1), 34.33 (C-7), 36.74 (C-4),
37.72 (C-10), 38.81 (C-22), 39.69 (C-11), 40.75 (C-8), 40.99 (C-17), 50.73 (C-5), 54.45 (C-9), 55.49 (C-13), 56.44 (C-14), 62.66
(C-6′), 68.98 (C-4′), 71.56 (C-5′), 71.97 (C-2′), 73.24 (C-3′), 78.01 (C-3), 82.21 (C-20), 94.60 (C-1′), 124.30 (C-24), 131.64 (C-25),
–
169.06, 169.56, 170.22, 170.62, 170.71 (5CH CO), 212.00 (C-12). HR-ESI-MS m/z 829.4754 [M – H] (calcd for C H O ,
3
46 69 13
829.4744).
3α-Hydroxydammar-24-en-12-one 3-O-β-D-glucopyranoside (11) was prepared via deacetylation of 7 by NaOMe
20
1
(0.1 N) in MeOH at 25°C (99% yield). C H O , amorph., [α] +14.9° (c 1.25, Ñ Í N). Í NMR spectrum (500 MHz,
36 60
8
D
5 5
C D N, δ, ppm, J/Hz): 0.555 (3Í, s, Ìå-30), 0.861 (3Í, s, Ìå-29), 0.873 (3Í, s, Ìå-19), 1.148 (3Í, s, Ìå-18), 1.250 (3Í, s,
5
5
Ìå-28), 1.402 (3Í, s, Ìå-21), 1.613 (3Í, s, Ìå-27), 1.665 (3Í, s, Ìå-26), 2.292 (1H, t, J = 13.3, H-11a), 2.371 (1H, dd,
J = 13.2, 4.3, H-11b), 2.679 (1Í, td, J = 9.9, 5.2, Í-17), 3.293 (1Í, d, J = 9.8, Í-13), 3.647 (1Í, br.s, H-3β), 3.953 (1H, m,
H-5′), 3.968 (1Í, t, J = 8.0, H-2′), 4.185 (1H, t, J = 9.0, H-4′, 3′), 4.228 (1H, t, J = 8.7, H-3′), 4.391 (1Í, dd, J = 11.5, 5.4,
13
H-6b′), 4.565 (1Í, dd, J = 11.5, 2.5, H-6a′), 4.827 (1Í, d, J
= 7.8, H-1′), 5.266 (1Í, t, J = 7.0, H-24). C NMR spectrum
1′,2′
(125 MHz, C D N, δ, ppm): 15.84 (C-18), 16.14 (C-19), 17.10 (C-30), 17.66 (C-27), 18.50 (C-6), 21.76 (C-2), 22.47 (C-29),
5
5
23.60 (C-23), 24.45 (C-16), 25.78 (C-26), 26.55 (C-21), 29.46 (C-28), 31.92 (C-15), 33.92 (C-1), 34.46 (C-7), 37.52 (C-4),
37.94 (C-10), 39.82 (C-11), 40.88 (C-8), 41.86 (C-22), 44.09 (C-17), 50.70 (C-5), 54.22 (C-9), 55.81 (C-14), 56.38 (C-13),
63.25 (C-6′), 72.11 (C-4′), 73.21 (C-20), 74.98 (C-2′), 78.32 (C-5′), 78.90 (C-3′), 82.24 (C-3), 102.62 (C-1′), 125.87 (C-24),
–
130.84 (C-25), 211.86 (C-12). HR-ESI-MS m/z 619.4217 [M – H] (calcd for C H O , 619.4215).
36 59
8
3α-Hydroxydammar-24-en-12-one 20-O-β-D-glucopyranoside (12) was prepared via deacetylation of 8 by NaOMe
20
1
(0.1 N) in MeOH at 25°C (99% yield). C H O , amorph., [α] +19.3° (c 0.9, Ñ Í N). Í NMR spectrum (500 MHz,
36 60
8
D
5 5
C D N, δ, ppm, J/Hz): 0.763 (3Í, s, Ìå-30), 0.897 (3Í, s, Ìå-29), 0.914 (3Í, s, Ìå-19), 1.195 (3Í, s, Ìå-28), 1.351 (3Í, s,
5
5
Ìå-18), 1.568 (3Í, s, Ìå-21), 1.615 (3Í, s, Ìå-26), 1.624 (3Í, s, Ìå-27), 2.367 (2Í, m, Í-11), 2.890 (1Í, td, J = 9.8, 4.3,
Í-17), 3.585 (1Í, br.s, H-3β), 3.627 (1Í, d, J = 9.5, Í-13), 3.889 (1H, m, H-5′), 3.994 (1Í, t, J = 7.8, H-2′), 4.215 (2H, m,
H-4′, 3′), 4.333 (1Í, dd, J = 11.5, 5.2, H-6b′), 4.477 (1Í, dd, J = 11.5, 2.7, H-6a′), 5.089 (1Í, d, J
= 7.6, H-1′), 5.205 (1Í,
1′,2′
13
t, J = 7.0, H-24). C NMR spectrum (125 MHz, C D N, δ, ppm): 16.25 (C-18), 16.46 (C-19), 17.08 (C-30), 17.95 (C-27),
5
5
18.88 (C-6), 22.55 (C-29), 22.72 (C-21), 24.18 (C-23), 24.72 (C-16), 25.96 (C-26), 26.58 (C-2), 29.54 (C-28), 32.44 (C-15),
34.16 (C-1), 35.06 (C-7), 38.29 (C-4), 38.36 (C-10), 40.31 (C-11), 40.84 (C-22), 41.35 (C-8), 42.76 (C-17), 49.84 (C-5),
881

55.02 (C-9), 56.49 (C-14), 56.54 (C-13), 63.22 (C-6′), 72.17 (C-4′), 75.30 (C-3), 75.94 (C-2′), 78.19 (C-5′), 79.46 (C-3′),
–
81.55 (C-20), 98.71 (C-1′), 125.98 (C-24), 131.02 (C-25), 211.50 (C-12). HR-ESI-MS m/z 619.4219 [M – H] (calcd for
C H O , 619.4215).
36 59
8
3α-Hydroxydammar-24-en-12-one 3,20-di-O-β-D-glucopyranoside (13) was prepared via deacetylation of 9 by
20
1
NaOMe (0.1 N) in MeOH at 25°C (99% yield). C H O , amorph., [α] +1.7° (c 0.4, Ñ Í N). Í NMR spectrum
42 70 13
D
5 5
(500 MHz, C D N, δ, ppm, J/Hz): 0.573 (3Í, s, Ìå-30), 0.847 (3Í, s, Ìå-29), 0.878 (3Í, s, Ìå-19), 1.243 (3Í, s, Ìå-28),
5
5
1.306 (3Í, s, Ìå-18), 1.547 (3Í, s, Ìå-21), 1.617 (6Í, s, Ìå-26, 27), 2.313 (2Í, m, Í-11), 2.869 (1Í, td, J = 9.8, 4.4, Í-17),
3.576 (1Í, d, J = 9.4, Í-13), 3.641 (1Í, br.s, H-3β), 3.891 (1H, m, H-5′′), 3.970 (3Í, m, H-5′′, 2′, 2′′), 4.209 (4H, m, H-4′, 3′,
4′′, 3′′), 4.331 (1Í, dd, J = 11.5, 5.3, H-6b′′), 4.392 (1Í, dd, J = 11.6, 5.4, H-6b′), 4.482 (1Í, dd, J = 11.5, 2.6, H-6a′′), 4.568
(1Í, dd, J = 11.5, 2.6, H-6a′), 4.827 (1Í, d, J
= 7.8, H-1′), 5.077 (1Í, d, J
= 7.6, H-1′′), 5.198 (1Í, t, J = 7.0, H-24).
1′,2′
1′,2′
13
C NMR spectrum (125 MHz, C D N, δ, ppm): 16.01 (C-18), 16.31 (C-19), 16.90 (C-30), 17.75 (C-27), 18.54 (C-6), 21.80
5
5
(C-2), 22.47 (C-29), 22.47 (C-21), 23.96 (C-23), 24.53 (C-16), 25.75 (C-26), 29.46 (C-28), 32.27 (C-15), 34.03 (C-1), 34.66
(C-7), 37.53 (C-4), 38.01 (C-10), 40.03 (C-11), 40.55 (C-22), 41.08 (C-8), 42.53 (C-17), 50.71 (C-5), 54.61 (C-9), 56.24
(C-14), 56.26 (C-13), 63.04 (C-6′′), 63.26 (C-6′), 71.98 (C-4′′), 72.12 (C-4′), 74.98 (C-2′), 75.74 (C-2′′), 78.00 (C-5′′), 78.32
(C-5′), 78.92 (C-3′), 79.26 (C-3′′), 81.35 (C-20), 82.29 (C-3), 98.50 (C-1′′), 102.65 (C-1′), 125.79 (C-24), 130.80 (C-25),
–
211.26 (C-12). HR-ESI-MS m/z 781.4741 [M – H] (calcd for C H O , 781.4744).
42 69 13
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