Journal of Medicinal Chemistry
ARTICLE
D2O exch.), 12.60 (s, 1H, 5-OH, D2O exch.). 13C NMR (DMSO-d6, 150
MHz): δ 14.68, 14.71, 63.55, 63.67, 63.71, 68.70, 71.08, 73.01, 73.41, 93.63,
98.65, 98.81, 103.92, 114.16, 114.40, 115.34, 115.73, 121.02, 121.68, 122.28,
122.40, 131.01, 132.80, 145.17, 148.77, 156.37, 156.50, 161.41, 162.47,
162.57, 164.26, 165.03, 165.17, 177.27. FAB-MS m/z [M þ H]þ ion = 761.
NMR (DMSO-d6, 150 MHz): δ 20.80, 20.82, 38.77, 38..28, 63.80, 68.60,
70.64, 72.90, 72.97, 93.73, 98.88, 99.25, 104.06, 115.30, 115.80, 120.96,
122.41, 128.92, 128.95, 129.16, 129.48, 131.15, 131.53, 133.24, 133.79,
135.82, 135.94, 145.13, 150.66, 156.56, 161.51, 164.40, 170.88, 171.01,
177.24. FAB-MS m/z [M þ H]þ ion = 729. Anal. calcd for C39H36O14:
C, 64.28; H, 4.98. Found: C, 64.46; H, 4.71.
Anal. calcd for C39H36O16 1/4H2O: C, 61.22; H, 4.81 Found: C, 61.11;
3
H, 4.68.
2-(30,40-Dihydroxyphenyl)-5,7-dihydroxy-3-β-D-[200,600-di-O-(4-fluoro-
phenylacetyl)]galactosyl-4H-chromen-4-one (5e). Yield, 0.57 g (77%).
1H NMR (DMSO-d6, 600 MHz): δ 3.37/3.45 (each AB system, each d,
JAB = 15.6 Hz, 2H, PhCH2CO), 3.67 (br s, 1H, 400-H), 3.70ꢀ3.74 (m, 4H,
2-(30,40-Dihydroxyphenyl)-5,7-dihydroxy-3-β-D-[200,600-di-O-(4-pro-
pylbenzoyl])]galactosyl-4H-chromen-4-one (5b). Yield, 0.59 g (79%).
1H NMR (DMSO-d6, 600 MHz): δ 0.86 and 0.88 (each t, each 3H, J =
7.2 Hz, 2 ꢁ CH3CH2), 1.531.63 (m, 4H, 2 ꢁ CH3CH2CH2), 2.55 and
2.62 (each t, each 2H, J = 7.2 Hz, 2 ꢁ CH3CH2CH2), 3.81 (br s, 1H, 400-
PhCH2CO, 300-H, 500-H), 3.99 (dd, J5 ,6 Hb = 4.2 Hz, Jgem = 11.4 Hz, 1H,
00 00
600-Hb), 4.04 (dd, J5 ,6 Ha = 3.0 Hz, Jgem = 11.4 Hz, 1H, 600-Ha), 5.010(0 br s,
00 00
H), 3.86ꢀ3.89 (m, 1H, 500-H), 3.93 (dd, J2 ,3 = 8.4 Hz, J3 ,4 = 4.8 Hz,
300-OH, D2O exch.), 5.11 (dd, J1 ,2 = 7.8 Hz, J2 ,3 = 7.2 Hz, 1H, 2 -H),
00 00
00 00
00 00
00 00
1H, 300-H), 4.23 (dd, J5 ,6 Hb = 3.0 Hz, Jgem = 11.4 Hz, 1H, 600-Hb), 4.29
5.20 (br s, 400-OH, D2O exch.), 5.50 (d, J1 ,2 = 7.8 Hz, 1H, 1 -H), 6.19 (d,
00
00 00
00 00
(dd, J5 ,6 Ha = 4.2 Hz, Jgem = 11.4 Hz, 1H, 600-Ha), 5.15 (d, J = 4.2 Hz, 300-
4J= 2.4 Hz, 1H, 8-H), 6.40 (d, 4J= 2.4 Hz, 1H, 6-H), 6.76 (d, J =8.4 Hz, 1H,
50-H), 6.99 and 7.04 (each t, each 2H, J = 9.0 Hz, 2 ꢁ 30000-H, 2 ꢁ 50000-H),
7.07 and 7.30 (each dd, each 2H, J = 8.4 Hz, J = 9.0 Hz, 2 ꢁ 20000-H, 2 ꢁ
00 00
OH, D2O exch.), 5.27 (d, J = 6.6 Hz, 400-OH, D2O exch.), 5.36 (dd,
00
00 00
00 00
00 00
J1 ,2 = 7.8 Hz, J2 ,3 = 8.4 Hz, 1H, 2 -H), 5.84 (d, J1 ,2 = 7.8 Hz, 1H,
100-H), 6.16 (d, 4J = 2.4 Hz, 1H, 8-H), 6.30 (d, 4J = 2.4 Hz, 1H, 6-H), 6.80
(d, J = 8.4 Hz, 1H, 50-H), 7.05 and 7.34 (each d, each 2H, each J = 8.4 Hz,
2 ꢁ 3000-H, 2 ꢁ 5000-H), 7.39 (d, 4J = 2.4 Hz, 1H, 20-H), 7.56 and 7.94
(each d, each 2H, each J = 9.0 Hz, 2 ꢁ 2000-H, 2 ꢁ 6000-H), 7.62 (dd, J =
8.4 Hz, 4J = 2.4 Hz, 1H, 60-H), 9.14 (s, 1H, 30-OH, D2O exch.), 9.80 (s,
1H, 40-OH, D2O exch.), 10.85 (s, 1H, 7-OH, D2O exch.), 12.59 (s, 1H,
5-OH, D2O exch.). 13C NMR (DMSO-d6, 150 MHz): δ 13.74, 13.78,
23.79, 24.01, 37.33, 63.75, 68.69, 71.04, 73.23, 73.34, 93.65, 98.62, 98.86,
103.94, 115.36, 115.75, 121.02, 122.36, 127.24, 127.82, 128.58, 128.76,
128.98, 129.01, 129.70, 132.79, 145.18, 148.08, 148.18, 148.79, 156.34,
161.41, 164.34, 165.37, 165.51, 177.26. FAB-MS m/z [M þ H]þ ion =
757. Anal. calcd for C41H40O14: C, 65.07; H, 5.33. Found: C, 65.01;
H, 5.48.
6
0000-H), 7.45 (d, 4J = 2.4 Hz, 1H, 20-H), 7.60 (dd, J = 8.4 Hz, 4J = 2.4 Hz,
1H, 60-H), 9.14 (s, 1H, 30-OH, D2Oexch.), 9.79 (s, 1H, 40-OH, D2Oexch.),
10.88 (s, 1H, 7-OH, D2O exch.), 12.68 (s, 1H, 5-OH, D2O exch.). 13C
NMR (DMSO-d6, 150 MHz): δ 31.36, 31.72, 63.97, 68.70, 70.84, 73.10,
73.22, 93.95, 99.10, 99.54, 104.22, 115.21, 115.35, 115.49, 116.01, 121.14,
122.58, 130.64, 131.04, 131.48, 131.33, 131.72, 131.77, 133.48, 134.23,
145.33, 149.02, 156.63, 160.69, 161.66, 162.30, 164.63, 170.90, 171.04,
177.45. FAB-MS m/z [M þ H]þ ion = 737. Anal. calcd for C37H30O14F2:
C, 60.33; H, 4.10. Found: C, 60.05; H, 4.15.
2-(30,40-Dihydroxyphenyl)-5,7-dihydroxy-3-β-D-{200,600-di-O-[3000-(4-
hydroxyphenylpropanoyl)]}galactosyl-4H-chromen-4-one (5f). Yield,
0.60 g (79%). 1H NMR (DMSO-d6, 600 MHz): δ 2.29 and 2.46 (each t,
each 2H, J = 7.8 Hz, 2 ꢁ PhCH2CH2CO), 2.55 and 2.73 (each t, each 2H,
J = 7.8 Hz, 2 ꢁ PhCH2CH2CO), 3.66ꢀ3.70 (m, 3H, 300-H, 400-H, 500-H),
2-(30,40-Dihydroxyphenyl)-5,7-dihydroxy-3-β-D-[200,600-di-O-(4-fluoro-
1
3.95 (dd, J5 ,6 Hb = 4.2 Hz, Jgem = 11.4 Hz, 1H, 600-Hb), 4.01 (dd, J5 ,6 Ha
=
00 00
00 00
benzoyl)]galactosyl-4H-chromen-4-one (5c). Yield, 0.53 g (75%). H
NMR (DMSO-d6, 600 MHz): δ 3.82 (br s, 1H, 400-H), 3.86ꢀ3.89 (m,
4.8 Hz, Jgem = 11.4 Hz, 1H, 600-Ha), 4.99 (d, J = 4.2 Hz, 300-OH, D2O exch.0)0 ,
00
00
1H, 500-H), 3.93 (dd, J2 , 3 = 8.4 Hz, J3 , 4 = 4.2 Hz, 1H, 3 -H), 4.26 (dd,
5.11 (dd, J1 ,2 = 7.8 Hz, J2 ,3 = 7.2 Hz, 1H, 2 -H), 5.14 (d, J = 4.2 Hz, 4 -
00 00
00 00
00 00
00 00
4
00
J5 ,6 Hb = 4.2 Hz, Jgem = 11.4 Hz, 1H, 600-Hb), 4.34 (dd, J5 ,6 Ha = 3.0 Hz,
00 00
00 00
00 00
OH, D2O exch.), 5.52 (d, J1 ,2 = 7.8 Hz, 1H, 1 -H), 6.14 (d, J = 1.8 Hz,
1H, 8-H), 6.34 (d, 4J = 1.8 Hz, 1H, 6-H), 6.57 and 6.60 (each d, each 2H,
each J=8.4Hz, 2ꢁ 30000-H, 2 ꢁ 50000-H), 6.79(d,J= 8.4 Hz, 1H, 50-H), 6.81
and 6.99 (each d, each 2H, each J = 8.4 Hz, 2 ꢁ 20000-H, 2 ꢁ 60000-H), 7.44
(d, 4J = 2.4 Hz, 1H, 20-H), 7.61 (dd, J = 8.4 Hz, 4J = 2.4 Hz, 1H, 60-H), 9.10
and 9.13 (each s, each 1H, 2 ꢁ OHPh, D2O exch.), 9.28 (s, 1H, 30-OH,
D2O exch.), 9.79 (s, 1H, 40-OH, D2O exch.), 10.83 (s, 1H, 7-OH, D2O
exch.), 12.65 (s, 1H, 5-OH, D2O exch.). 13C NMR (DMSO-d6, 150 MHz):
δ 29.57, 29.61, 35.65, 36.02, 63.21, 68.54, 70.61, 72.54, 73.02, 93.68, 95.77,
99.12, 104.01, 115.20, 115.22, 115.33, 115.81, 121.02, 122.41, 129.12,
129.28, 130.52, 130.87, 133.22, 145.15, 148.79, 155.70, 155.89, 156.52,
161.42, 164.36, 171.85, 171.96, 177.30. FAB-MS m/z [M þ H]þ ion = 761.
Anal. calcd for C39H36O16: C, 61.58; H, 4.77. Found: C, 61.52; H, 4.97.
2-(30,40-Dihydroxyphenyl)-5,7-dihydroxy-3-β-D-{200,600-di-O-[3000-(4-
ethoxyphenylpropanoyl)]}galactosyl-4H-chromen-4-one (5g). Yield,
0.68 g (83%). 1H NMR (DMSO-d6, 600 MHz): δ 1.21 and 1.29 (each
t, each 3H, J = 7.8 Hz, 2 ꢁ CH3CH2), 2.30 and 2.52 (each t, each 2H, J =
7.8 Hz, 2 ꢁ PhCH2CH2CO), 2.59 and 2.78 (each t, each 2H, J = 7.8 Hz,
2 ꢁ PhCH2CH2CO), 3.65ꢀ3.70 (m, 3H, 300-H, 400-H, 500-H), 3.82 and
Jgem = 11.4 Hz, 1H, 600-Ha), 5.17 (d, J = 4.2 Hz, 300-OH, D2O exch.), 5.31
(d, J = 6.6 Hz, 1H, 400-OH, D2O exch.), 5.34 (dd, J1 ,2 = 7.8 Hz, J2 ,3
=
00 00
00 00
4
00
8.4 Hz, 1H, 200-H), 5.74 (d, J1 ,2 = 7.8 Hz, 1H, 1 -H), 6.13 (d, J = 2.4 Hz,
1H, 8-H), 6.28 (d, 4J = 2.4 Hz, 1H, 6-H), 6.78 (d, J = 8.4 Hz, 1H, 50-H),
7.09 and 7.36 (each t, each 2H, J = 9.0 Hz, 2 ꢁ 3000-H, 2 ꢁ 5000-H), 7.37 (d,
4J = 2.4 Hz, 1H, 20-H), 7.58 (dd, J = 8.4 Hz, 4J = 2.4 Hz, 1H, 60-H), 7.73
and 8.07 (each dd, each 2H, J = 8.4 Hz, J = 9.0 Hz, 2 ꢁ 2000-H, 2 ꢁ 6000-H),
9.14 (s, 1H, 30-OH, D2O), 9.79 (s, 1H, 40-OH, D2O exch.), 10.84 (s, 1H,
7-OH, D2O exch.), 12.54 (s, 1H, 5-OH, D2O exch.). 13C NMR (DMSO-
d6, 150 MHz): δ 63.85, 68.59, 70.96, 73.29, 73.56, 93.61, 98.84, 99.47,
103.87, 115.33, 115.64, 115.76, 115.79, 115.84, 115.98, 120.94, 122.29,
126.20, 126.80, 131.73, 131.80, 132.43, 132.88, 145.13, 148.77, 156.31,
164.52, 164.95, 161.32, 164.28, 164.44, 164.49, 177.17. FAB-MS m/z [M
þ H]þ ion = 709. Anal. calcd for C35H26O14F2: C, 59.33; H, 3.70. Found:
C, 58.12; H, 4.01.
00 00
2-(30,40-Dihydroxyphenyl)-5,7-dihydroxy-3-β-D-[200,600-di-O-(4-meth-
ylphenylacetyl)]galactosyl-4H-chromen-4-one (5d). Yield, 0.58 g
(79%). 1H NMR (DMSO-d6, 600 MHz): δ 2.20 and 2.21 (each s, each
3H, 2 ꢁ CH3Ph), 3.30/3.37 (each AB system, each d, each JAB = 15.6
Hz, 2H, PhCH2CO), 3.66 (br s, 2H, PhCH2CO), 3.69ꢀ3.72 (m, 2H,
00 00
3.92 (each q, each 2H, J = 7.2 Hz, 2 ꢁ CH3CH2), 3.95 (dd, J5 ,6 Hb = 4.2
Hz, Jgem = 11.4 Hz, 1H, 600-Hb), 4.01 (dd, J5 ,6 Ha = 4.8Hz, Jgem = 11.4 Hz,
00 00
1H, 600-Ha), 5.00 (d, J = 4.2 H0z0, 1H, 300-OH, D2O exch.), 5.110(0dd, J1 ,2
=
400-H, 500-H), 3.97ꢀ4.04 (m, 3H, 300-H, 600-H), 5.00 (d, J = 4.8 Hz, 1H,
00 00
00
300-OH), 5.105 (dd, J1 ,2 = 7.8 Hz, J2 ,3 = 6.6 Hz, 1H, 2 -H), 5.18 (d,
00 00
8.4 Hz, J2 ,3 = 7.8 Hz, 1H, 2 -H), 5.16 (d, J = 5.4 Hz, 1H, 4 -OH, D2O
exch.), 5.55 (d, J1 ,2 = 8.4 Hz, 1H, 1 -H), 6.14 (d, J = 1.8 Hz, 1H, 8-H),
00 00
00 00
4
00
4
J = 6.0 Hz, 1H, 400-OH), 5.54 (d, J1 ,2 = 7.8 Hz, 1H, 1 -H), 6.20 (d, J =
00
00 00
00 00
6.31 (d, 4J = 1.8 Hz, 1H, 6-H), 6.66 and 6.70 (each d, each 2H, each J = 9.0
Hz, 2 ꢁ 30000-H, 2 ꢁ 50000-H), 6.80 (d, J = 8.4 Hz, 1H, 50-H), 6.89 and
7.08 (each d, each 2H, each J = 9.0 Hz, 2 ꢁ 20000-H, 2 ꢁ 60000-H), 7.43 (d,
4J = 2.4 Hz, 20-H), 7.62 (dd, J = 8.4 Hz, 4J = 2.4 Hz, 1H, 60-H), 9.14 (s, 1H,
30-OH, D2O exch.), 9.81 (s, 1H, 40-OH, D2O exch.), 10.82 (s, 1H, 7-OH,
D2O), 12.65 (s, 1H, 5-OH, D2O). 13C NMR (DMSO-d6, 150 MHz): δ
2.4 Hz, 1H, 8-H), 6.40 (d, 4J = 1.8 Hz, 1H, 6-H), 6.78 (d, J = 8.4 Hz, 1H,
50-H), 6.90 and 6.96 (each d, each 2H, J = 8.4 Hz, 2 ꢁ 30000-H, 2 ꢁ 50000
-
H), 7.04 and 7.14 (each d, each 2H, J = 8.4 Hz, 2 ꢁ 20000-H, 2 ꢁ 60000-H),
7.45 (d, 4J = 2.4 Hz, 1H, 20-H), 7.61 (dd, J = 8.4 Hz, 4J = 2.4 Hz, 1H, 60-
H), 9.13 (s, 1H, 30-OH, D2O exch.), 9.78 (s, 1H, 40-OH, D2O exch.),
10.87 (s, 1H, 7-OH, D2O exch.), 12.70 (s, 1H, 5-OH, D2O exch.). 13
C
3699
dx.doi.org/10.1021/jm200010x |J. Med. Chem. 2011, 54, 3686–3703