R. R. Schmidt et al.
FULL PAPER
69.6 (1 C, C-2b), 70.4 (1 C, C-5b), 71.1 (1 C, C-3b), 75.4 (1 C,
CH2Ph), 77.2 (1 C, C-2a), 81.5 (1 C, C-4a), 82.8 (1 C, C-3a), 90.7
(1 C, C-3), 100.1 (1 C, C-1b), 101.1 (1 C CHPh), 104.4 (1 C, C-
1a), 125.9, 128.3, 128.6, 130.0 (10 C, 2×Ph), 128.0 (1 C, C-12),
29-CH3), 1.15–1.19 (m, 1 H, 16-Hb), 1.27–1.30 (m, 2 H, 22-Ha, 21-
Ha), 1.35 (s, 3 H, 27-CH3), 1.39–1.42 (m, 3 H, 22-Hb, 7-Ha, 6-Ha),
1.58–1.64 (m, 3 H, 6-Hb, 19-Ha, 7-Hb), 1.75–1.91 (m, 4 H, 2-Ha,b
,
15-Ha, 19-Hb), 1.99–2.08 (m, 13 H, 19-Hb, 21-Hb, 15-Hb, 3×Ac,
137.3, 138.0 (2 C, ipso-Ph), 169.1, 169.3, 170.1, 170.3 (5 C, C-13, 18-H), 2.14 (s, 3 H, Ac), 2.32 (s, 1 H, 9-H), 2.79 (brd, 1 H, 1-Hb),
4×CH3CO), 176.9 (1 C, C-30), 200.2 (1 C, C-11) ppm. MALDI- 3.16 (dd, J3,
= 4.9, J3,
= 10.8 Hz, 1 H, 3-H), 3.33–3.34 (m,
2-Ha
2-Hb
MS (positive mode, matrix DHB, THF): m/z = 1179 [M + Na]+,
1195 [M + K]+. C65H86O18 (1155.4): calcd. C 67.57, H 7.50; found
C 67.17, H 7.52.
1 H, 5a-H), 3.49 (brs, 3 H, 3 OH), 3.55–3.56 (m, 3 H, 2a-H, 3a-H,
4a-H), 3.69 (s, 3 H, OCH3), 3.79 (dd, Jgem = 11.8, J6,5 = 4.8 Hz, 1
H, 6a-Ha), 3.88 (dd, Jgem = 11.8, J6,5 = 3.5 Hz, 1 H, 6a-Hb), 3.92
(dd, J5,
= J5,
= 6.8 Hz, 1 H, 5b-H), 4.11–4.12 (m, 2 H, 6b-
6-Ha
6-Hb
Compound 17: TLC (petroleum ether/EtOAc 3:1): Rf = 0.48. [α]D
= +19.6 (c = 1, CHCl3). 1H NMR (600 MHz, CDCl3): δ = 0.77 (s,
3 H, 28-CH3), 0.82 (d, J5,6 = 11.2 Hz, 1 H, 5-H), 0.86 (s, 3 H, 24-
CH3), 0.97, 0.98 (2×s, 6 H, 25-CH3, 26-CH3), 1.02–1.03 (m, 4 H,
27-CH3, 16-Ha), 1.07 (s, 3 H, 23-CH3), 1.14 (s, 3 H, 27-CH3), 1.16–
1.60 (m, 11 H, 1-Ha, 7-Ha, 22-Ha, 7-Hb, 6-Ha, 15-Ha, 22-Hb, 21-
Ha, 15-Hb, 16-Hb, 6-Hb), 1.68–1.78 (m, 1 H, 2-Ha), 1.95–1.96 (m,
7 H, 2-Hb, 2×Ac), 2.00–2.03 (m, 10 H, 21-Hb, 3×Ac), 2.07, 2.14,
2.15 (3×s, 6 H, 3×Ac), 2.24–2.26 (m, 2 H, 9-H, 19-Ha), 2.47 (d,
Jgem = 11.2 Hz, 1 H, 19-Hb), 2.84 (br d, 1 H, 1-Hb), 3.15 (dd,
Ha,b), 4.45 (d, J1,2 = 5.6 Hz, 1 H, 1a-H), 4.99 (d, J1,2 = 7.9 Hz, 1
H, 1b-H), 5.01 (dd, J3,2 = 10.5, J3,4 = 3.1 Hz, 1 H, 3b-H), 5.23 (dd,
J2,1 = 8.0, J2,3 = 10.3 Hz, 1 H, 2b-H), 5.37 (d, J4,3 = 2.7 Hz, 1 H,
4b-H), 5.66 (s, 1 H, 12-H) ppm. 13C NMR (151 MHz, CDCl3): δ =
16.3, 16.4 (2 C, C-24, C-25), 17.4 (1 C, C-6), 18.7 (1 C, C-26), 20.6,
20.7, 21.0 (4 C, 4×CH3CO), 23.4 (1 C, C-27), 26.4, 26.5 (3 C, C-
2, C-15, C-16), 27.7 (1 C, C-23), 28.3, 28.5 (2 C, C-29, C-28), 31.1
(1 C, C-21), 32.7 (1 C, C-7), 37.7 (1 C, C-22), 39.2 (1 C, C-1), 41.1
(1 C, C-19), 48.4 (1 C, C-18), 51.8 (1 C, OCH3), 55.4 (1 C, C-5),
60.7 (1 C, C-6b), 61.8 (1 C, C-9), 62.6 (1 C, C-6a), 66.8 (1 C, C-
4b), 70.3 (1 C, C-2b), 70.6 (2 C, C-5b, C-3a), 74.7 (1 C, C-5a), 76.6
(1 C, C-2a), 80.3 (1 C, C-4a), 89.7 (1 C, C-3), 100.7 (1 C, C-1b),
103.7 (1 C, C-1a), 128.5 (1 C, C-12), 169.3, 170.1, 170.3 (4 C,
4×CH3CO), 176.9 (1 C, C-30), 200.2 (1 C, C-11) ppm. MALDI-
MS (positive mode, matrix DHB, THF): m/z = 1000 [M + Na]+,
1116 [M + K]+. C51H76O18·1H2O (995.2): calcd. C 61.55, H 7.59;
found C 61.74, H 8.11.
J3,
= 4.4, J3,
= 11.8 Hz, 1 H, 3-H), 3.44 (dd, J5,
= 5.1,
2-Ha
2-Hb
6-Hb
J5,
= J5,4 = 9.6 Hz, 1 H, 5b-H), 3.68–3.71 (m, 4 H, 4b-H,
6-Ha
OCH3), 3.75 (dd, J3,4 = J3,2 = 9.1 Hz, 1 H, 3b-H), 3.78–3.90 [m, 4
H, H,H-COSY: 3.78 (5c-H), 3.81 (6b-Ha), 3.85 (2b-H), 3.88 (6a-
Ha)], 4.04–4.08 [m, 3 H, H,H-COSY: 4.03 (6c-Ha), 4.05 (5a-H),
4.08 (6c-Hb)], 4.15 (dd, J6,5 = 5.3, Jgem = 11.2 Hz, 1 H, 6a-Hb),
4.44 (dd, J6,5 = 4.6, Jgem = 10.2 Hz, 1 H, 6b-Hb), 4.50 (d, J1,2
=
7.6 Hz, 1 H, 1b-H), 4.66 (d, Jgem = 10.3 Hz, 1 H, CH2Ph), 4.93 (d,
Jgem = 10.3 Hz, 1 H, CH2Ph), 4.96 (dd, J3,4 = 3.2, J3,2 = 10.5 Hz,
1 H, 3c-H), 5.06 (d, J1,2 = 7.9 Hz, 1 H, 1c-H), 5.18–5.23 (m, 2 H,
2c-H, 2a-H), 5.33 (d, J4,3 = 2.8 Hz, 1 H, 4c-H), 5.42 (brs, 1 H, 4a-
H), 5.45 (dd, J3,4 = 3.2, J3,2 = 10.8 Hz, 1 H, 3a-H), 5.55 (s, 1 H,
CHPh), 5.70 (d, J1,2 = 3.3 Hz, 1 H, 1a-H), 5.87 (s, 1 H, 12-H),
7.26–7.49 (m, 10 H, 2×Ph) ppm. ROESY: 5.70 (1a-H), 5.87 (12-
H). 13C NMR (151 MHz, CDCl3): δ = 15.8 (1 C, C-24), 17.4, 17.8,
17.9 (3 C, C-6, C-25, C-28), 19.5 (1 C, C-27), 20.0 (1 C, C-26), 20.5,
20.6, 20.7, 20.8 (8 C, 8×CH3CO), 24.7 (2 C, C-16, C-23), 27.0 (1
C, C-2), 27.7 (1 C, C-29), 30.2 (1 C, C-21), 32.5 (2 C, C-7, C-19),
36.7 (1 C, C-15), 37.7 (1 C, C-22), 40.8 (1 C, C-1), 51.7 (1 C,
OCH3), 55.0 (1 C, C-9), 55.9 (1 C, C-5), 61.2 (1 C, C-6c), 61.8 (1
C, C-6a), 65.7 (1 C, C-5b), 66.7 (1 C, C-5a), 67.2 (1 C, C-4c), 67.6
(1 C, C-3a), 67.7 (1 C, C-2a), 68.0 (1 C, C-4a), 68.8 (1 C, C-6b),
69.7 (1 C, C-2c), 70.3 (1 C, C-5c), 71.1 (1 C, C-3c), 77.0 (1 C,
CH2Ph), 77.2 (1 C, C-2b), 81.6 (1 C, C-4b), 82.8 (1 C, C-3b), 90.4
(1 C, C-3), 92.8 (1 C, C-1a), 100.2 (1 C, C-1c), 101.2 (1 C, CHPh),
102.8 (1 C, C-12), 104.5 (1 C, C-1b), 128.1, 128.3, 128.6, 129.0 (10
C, 2 ×Ph), 133.3 (1 C, C-18), 132.1 (1 C, C-13), 137.3, 137.9 (2 C,
ipso-Ph), 154.3 (1 C, C-11), 169.2, 169.3, 170.1, 170.2, 170.3, 170.4
(8 C, 8×CH3CO), 178.8 (1 C, C-30) ppm. MALDI-MS (positive
mode, matrix DHB, THF): m/z = 1508 [M + Na]+. C79H104O27
(1485.7): calcd. C 63.87, H 7.06; found C 63.85, H 7.30.
Methyl 3β-O-[(2,3,4,6-Tetra-O-acetyl-β-
D-galactopyranosyl)-(1Ǟ2)-
(4,6-O-benzylidene-β- -glucopyranosyl)]-18β-glycyrrhetinate (19):
D
Benzaldehyde dimethyl acetal (78 µL, 0.53 mmol) and p-toluenesul-
fonic acid (5 mg, 0.02 mmol) were added to a solution of 18
(410 mg, 0.45 mmol) in dry acetonitrile (27 mL). The reaction mix-
ture was stirred for 2 h and quenched with NEt3, and the solvents
were evaporated. Purification by flash chromatography (petroleum
ether/EtOAc 2:1) afforded 19 (403 mg, 85 %). TLC (petroleum
ether/EtOAc 1:1): Rf = 0.40. [α]D = +19.6 (c = 0.2, CHCl3). 1H
NMR (600 MHz, CDCl3): δ = 0.71 (d, J5,6 = 11.6 Hz, 1 H, 5-H),
0.80 (s, 3 H, 28-CH3), 0.87 (s, 3 H, 24-CH3), 0.94–0.96 (m, 1 H, 1-
Ha), 1.02 (brd, 1 H, 16-Ha), 1.2 (s, 6 H, 26-CH3, 23-CH3), 1.15 (s,
6 H, 25-CH3, 23-CH3), 1.18–1.19 (m, 1 H, 16-Hb), 1.30–1.32 (m, 2
H, 21-Ha, 22-Ha), 1.35 (s, 3 H, 27-CH3), 1.39–1.44 (m, 3 H, 7-Ha,
22-Hb, 6-Ha), 1.58–1.64 (m, 3 H, 6-Hb, 19-Ha, 7-Hb), 1.77–1.83 (m,
3 H, 2-Ha,b, 15-Ha), 1.91–1.93 (m, 1 H, 19-Hb), 2.03, 2.06 (3×s, 9
H, 3×Ac), 2.07–2.08 (m, 1 H, 18-H), 2.13 (s, 3 H, Ac), 2.32 (s, 1
H, 9-H), 2.54 (d, JOH,3 = 2.1 Hz, 1 H, 3-OH), 2.79 (brd, 1 H, 1-
Hb), 3.15 (dd, J3,
= 5.7, J3,
= 10.5 Hz, 1 H, 3-H), 3.38 (ddd,
2-Ha
2-Hb
J5,4 = J5,
= 9.4, J5,
= 4.7 Hz, 1 H, 5a-H), 3.51 (dd, J4,3 =
6-Ha
6-Hb
J4,5 = 9.3 Hz, 1 H, 4a-H), 3.69 (s, 3 H, OCH3), 3.75–3.78 (m, 2 H,
2a-H, 6a-Ha), 3.81 (ddd, J3,4 = J3,2 = 9.0, J3,OH = 1.9 Hz, 1 H, 3a-
H), 4.31 (dd, J5,
= J5,
= 6.7 Hz, 1 H, 5b-H), 4.11–4.12 (m,
6-Ha
6-Hb
Methyl 3β-O-[(2,3,4,6-Tetra-O-acetyl-β-
D
-galactopyranosyl)-(1Ǟ2)-
2 H, 6b-Ha,b), 4.31 (dd, Jgem = 10.5, J6,5 = 5.0 Hz, 1 H, 6a-Hb),
4.50 (d, J1,2 = 7.4 Hz, 1 H, 1a-H), 5.01–5.04 (m, 2 H, 1b-H, 3b-H),
(β- -glucopyranosyl)]-18β-glycyrrhetinate (18): Palladium on car-
D
bon (280 mg, 10% Pd) was added to a solution of compound 16
(514 mg, 0.45 mmol) in a mixture of CH3OH/CH2Cl2 (2.2:1,
37 mL) and the suspension was vigorously stirred under hydrogen
at room temp. After 2 h the mixture was filtered and the filtrate
was concentrated in vacuo. The residue was purified by flash
chromatography (petroleum ether/EtOAc 2:1) to afford 18 (410 mg,
qu) as a white powder. TLC (petroleum ether/EtOAc 1:1): Rf =
5.18 (dd, J2,3 = 8.0, J2,1 = 10.3 Hz, 1 H, 2b-H), 5.36 (d, J4,3 =
2.7 Hz, 1 H, 4b-H), 5.51 (s, 1 H, CHPh), 5.66 (s, 1 H, 12-H), 7.37–
7.49 (m, 5 H, Ph) ppm. 13C NMR (151 MHz, CDCl3): δ = 16.3,
16.4 (2 C, C-24, C-25), 17.4 (1 C, C-6), 18.7 (1 C, C-26), 20.6, 21.0
(4 C, 4×CH3CO), 23.4 (1 C, C-27), 26.1, 26.4, 26.5 (3 C, C-2, C-
15, C-16), 27.6 (1 C, C-23), 28.3, 28.5 (2 C, C-28, C-29), 31.4 (1 C,
C-21), 32.9 (1 C, C-7), 37.9 (1 C, C-22), 39.1 (1 C, C-1), 41.1 (1 C,
C-19), 48.4 (1 C, C-18), 51.8 (1 C, OCH3), 55.4 (1 C, C-5), 61.0 (1
1
0.17. [α]D = +7.9 (c = 1, CHCl3). H NMR (600 MHz, CDCl3): δ
= 0.72 (d, J5,6 = 11.6 Hz, 1 H, 5-H), 0.80 (s, 3 H, 28-CH3), 0.86 (s, C, C-6b), 61.8 (1 C, C-9), 65.7 (1 C, C-5a), 67.0 (1 C, C-4b), 68.9
3 H, 24-CH3), 0.94–0.96 (m, 1 H, 1-Ha), 1.00 (brd, 1 H, 16-Ha), (1 C, C-6a), 69.9 (1 C, C-2b), 70.4 (1 C, C-5b), 71.0 (1 C, C-3b),
1.09 (s, 3 H, 23-CH3) 1.12 (s, 3 H, 26-CH3), 1.14 (s, 6 H, 25-CH3,
74.6 (1 C, C-3a), 79.5 (1 C, C-2a), 80.4 (1 C, C-4a), 90.3 (1 C, C-
5300
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Eur. J. Org. Chem. 2006, 5293–5304