The Journal of Organic Chemistry
Article
1-O-(3,4,5-Tri-O-benzylgalloyl)-2,3-O-(R)-[4,4′,5,5′,6,6′-hexa-
benzyloxy-1,1′-biphenyl-2,2′-dicarboxylate]-6-O-(S)-
[4,4′,5,5′,6,6′-hexabenzyloxy-1,1′-biphenyl-2-carboxylate-2′-
carboxylic acid]-β-D-glucopyranose (13). To a stirred solution of
(S)-124 (prepared from 226 μmol of 10) and Et3N (14.2 mg, 140
μmol) in CH2Cl2 (0.8 mL) was added a solution of diol 7 (98.2 mg,
67.9 μmol) in CH2Cl2 (1.5 mL) at rt. After being stirred for 6 d at rt,
the reaction was quenched by addition of H2O (1 mL). The aq
mixture was extracted with AcOEt. The combined organic layer was
washed with brine. After the general drying procedure, the crude
product was purified by CC (5 g of SiO2, n-hexane/AcOEt = 75/25 to
65/35) to afford 13 (106 mg, 67%) as a colorless oil: [α]D23 −19.6 (c
0.45, CHCl3); IR 3462 3090, 3064, 3032, 2927, 2874, 2859, 1732,
1589, 1497, 1481, 1455, 1430, 1410, 1369, 1334, 1238, 1213, 1192,
1095, 1028, 972, 909, 848, 751, 696; 1H NMR 7.72 (s, 1 H), 7.69 (s, 1
H), 7.65−7.52 (m, 13 H), 7.46−7.13 (m, 54 H), 6.96−6.86 (m, 10 H),
6.75−6.73 (m, 2 H), 5.81 (d, J = 7.6 Hz, 1 H), 5.38−5.28 (m, 6 H),
5.24 (d, J = 11.7 Hz, 1 H), 5.18−4.81 (m, 22 H), 4.69 (d, J = 11.5 Hz,
1 H), 4.60−4.54 (m, 3 H), 4.29 (dd, J = 12.1, 5.5 Hz, 1 H), 3.91−3.77
(m, 2 H); 13C NMR 169.7 (s), 168.6 (s), 167.1 (s), 166.7 (s), 164.8
(s), 153.6 (s, 2 C), 153.5 (s), 153.4 (s), 153.1 (s, 2 C), 152.7 (s), 152.4
(s), 151.9 (s), 151.8 (s), 147.7 (s), 146.5 (s), 146.0 (s), 144.7 (s),
143.7 (s), 139.0 (s), 138.9 (s), 138.8 (s), 138.7 (s), 138.6 (s), 138.6
(s), 138.5 (s), 138.4 (s), 138.3 (s), 138.2 (s), 138.2 (s), 137.8 (s, 2 C),
137.8 (s), 137.5 (s), 129.5−128.2 (overlapping 75 doublets and 2
singlets: 20 peaks were observed), 127.9 (s), 127.2 (s), 126.5 (s),
125.6 (s), 124.9 (s), 123.8 (s), 123.3 (s), 112.1 (d), 112.0 (d), 110.1
(d, 4 C), 92.9 (d), 82.3 (d), 76.7 (d), 75.9 (t), 75.9 (t, 2 C), 75.7 (t, 2
C), 75.7 (t), 75.5 (t), 75.2 (t), 75.1 (t), 72.7 (d), 71.8 (t), 71.7 (t),
71.7 (t), 71.6 (t), 71.4 (t), 71.0 (t), 68.4 (d), 64.0 (t); HRMS (ESI-
TOF) m/z: [M − H]− Calcd for C146H119O27 2303.7939, found
2303.7880.
sample of natural cuspinin; for their comparison, see Supporting
Information.
(R)-4,4′,5,5′,6,6′-Hexakisbenzyloxy-1,1′-biphenyl-2,2′-dicar-
boxylic Acid Anhydride ((R)-12). To a stirred solution of
dicarboxylic acid (R)-1025 (163 mg, 186 μmol) in toluene (1.9 mL)
and DMF (17 μL) was added (COCl)2 (28 mg, 223 μmol). After
being stirred for 40 min at 70 °C, the mixture was concentrated. To
the resulting residue was added toluene and the solution was
concentrated to azeotropically remove excess (COCl)2. This
procedure was repeated three times to provide (R)-12 as a yellow
21
1
syrup: [α]D −14.0 (c 1.02, CHCl3). H and 13C NMR data for (R)-
12 was identical to the literature data.4 The crude product was used for
the next reaction without further purification.
4,6-O-Anisylidene-3-O-(3,4,5-tri-O-benzylgalloyl)-1-O-(R)-
[4,4′,5,5′,6,6′-hexabenzyloxy-1,1′-biphenyl-2-carboxylate-2′-
carboxylic acid]-β-D-glucopyranose (16). To a stirred solution of
(R)-12 (prepared from 186 μmol of (R)-10 as described above) in
CH2Cl2 (0.4 mL) was added a mixture of diol 154 (31.5 mg, 43.7
μmol) and Et3N (12.1 mg, 120 μmol) in CH2Cl2 (0.9 mL). After
being stirred for 19.5 h at 50 °C, the reaction was quenched by
addition of saturated aq NH4Cl (3 mL). The aq mixture was extracted
with AcOEt. The combined organic layer was washed with brine. After
the general drying procedure, the crude product was purified by CC (3
g of SiO2, n-hexane/AcOEt = 80/20 to 70/30, followed by SiO2 1.5 g,
n-hexane/CHCl3 = 25/75) to afford 16 (48.3 mg, 76% yield) as a
22
colorless oil: [α]D −15.5 (c 0.925, CHCl3); IR 3734−3088, 3062,
3031, 2957, 2878, 2837, 1738, 1713, 1589, 1519, 1497, 1455, 1250,
1213, 1186, 1077, 1029, 1002, 909, 835, 752, 696; 1H NMR 7.78 (s, 1
H), 7.75 (s, 1 H), 7.61−7.59 (m, 4 H), 7.50−7.17 (m, 41 H), 6.95−
6.92 (m, 4 H), 6.85 (d, J = 8.7 Hz, 2 H), 5.84 (d, J = 7.8 Hz, 1 H), 5.53
(dd, J = 9.2, 9.2 Hz, 1 H), 5.51 (s, 1 H), 5.35 (s, 2 H), 5.28 (s, 2 H),
5.16 (d, J = 11.7 Hz, 2 H), 5.13−5.05 (m, 7 H), 5.02 (d, J = 11.0 Hz, 1
H), 4.97 (d, J = 11.0 Hz, 1 H), 4.94 (d, J = 10.8 Hz, 1 H), 4.83 (d, J =
11.0 Hz, 2 H), 4.21 (dd, J = 9.6, 3.9 Hz, 1 H), 3.84−3.60 (m, 7 H);
13C NMR 167.5 (s), 165.7 (s), 165.1 (s), 161.0 (s), 153.5 (s, 2 C),
1-O-(3,4,5-Tri-O-benzylgalloyl)-2,3-O-(R)-[4,4′,5,5′,6,6′-hexa-
benzyloxy-1,1′-biphenyl-2,2′-dicarboxylate]-4,6-O-(S)-
[4,4′,5,5′,6,6′-hexabenzyloxy-1,1′-biphenyl-2,2′-dicarboxy-
late]-β-D-glucopyranose (14). To a stirred solution of 13 (106 mg,
45.8 μmol) in CH2Cl2 (1 mL) were added DMAP (11.3 mg, 92.5
μmol) and EDCI·HCl (27.3 mg, 142 μmol). After being stirred for 1 d
at rt, the mixture was added H2O (2 mL). The aq mixture was
extracted with AcOEt. The combined organic layer was washed with
brine. After the general drying procedure, the crude product was
purified by CC (2 g of SiO2, n-hexane/AcOEt = 80/20) to afford 14
(34.5 mg, 41% yield) as a colorless oil: [α]D22 −44.4 (c 1.03, CHCl3);
IR 3066, 3031, 3018, 2933, 2877, 1750, 1590, 1497, 1455, 1429, 1413,
152.8 (s), 152.6 (s), 152.0 (s), 151.7 (s), 147.1 (s), 146.6 (s), 143.3
(s), 138.9 (s), 138.8 (s, 2 C), 138.8 (s), 138.5 (s), 138.5 (s), 138.2 (s),
138.0 (s, 2 C), 130.9 (s), 130.0 (s), 129.4−128.2 (overlapping 47
doublets and 1 singlet: 26 peaks were observed), 126.9 (s), 126.1 (s),
125.3 (s), 114.1 (d, 2 C), 112.7 (d), 112.5 (d), 109.9 (d, 2 C), 102.2
(d), 95.8 (d), 79.4 (d), 75.9 (t, 2 C), 75.6 (d), 75.5 (t), 75.2 (t), 75.2
(t), 72.9 (d), 72.0 (t), 71.9 (t), 71.8 (t, 2 C), 69.0 (t), 67.5 (d), 55.5
(q); HRMS (ESI-TOF) m/z: [M − H]− Calcd for C98H83O20
1579.5478, found 1579.5421.
1
1366, 1331, 1216, 1184, 1096, 1073, 1029, 1006, 910, 750; H NMR
4,6-O-Anisylidene-3-O-(3,4,5-tri-O-benzylgalloyl)-1,2-O-(R)-
[4,4′,5,5′,6,6′-hexabenzyloxy-1,1′-biphenyl-2,2′-dicarboxy-
late]-β-D-glucopyranose (17). To a stirred solution of 16 (585 mg,
370 μmol) in CH2Cl2 (3.7 mL) were added DMAP (50.4 mg, 413
μmol) and EDCI·HCl (212 mg, 1.11 mmol). After being stirred for 3
h at rt, the mixture was added H2O (10 mL). The aq mixture was
extracted with AcOEt. The combined organic layer was washed with
brine. After the general drying procedure, the crude product was
purified by CC (20 g of SiO2, n-hexane/AcOEt = 80/20 to 75/25) to
(55 °C) 7.66 (s, 2 H), 7.63 (s, 1 H), 7.54−6.86 (m, 78 H), 6.16 (d, J =
8.0 Hz, 1 H), 5.44−4.82 (m, 31 H), 4.64 (d, J = 10.8 Hz, 1 H), 4.62
(d, J = 10.8 Hz, 1 H), 4.53 (dd, J = 9.6, 6.4 Hz, 1 H), 4.46 (d, J = 11.2
Hz, 1 H), 4.06 (d, J = 13.3 Hz, 1 H); 13C NMR (55 °C) 168.1 (s),
167.9 (s), 167.7 (s), 167.7 (s), 164.8 (s), 154.2 (s), 154.0 (s, 2 C),
153.8 (s, 2 C), 153.7 (s), 153.4 (s), 153.4 (s), 153.1 (s), 152.8 (s),
147.3 (s), 147.1 (s), 145.8 (s), 145.6 (s), 144.9 (s), 138.9 (s), 138.8 (s,
2 C), 138.8 (s, 2 C), 138.7 (s), 138.7 (s), 138.5 (s, 2 C), 138.0 (s, 2
C), 137.9 (s), 137.8 (s, 2 C), 137.5 (s), 130.0 (s), 129.8 (s), 129.5−
128.3 (overlapping 75 doublets and 3 singlets: 55 peaks were
observed), 127.6 (s), 127.0 (s), 124.9 (s), 124.6 (s), 112.2 (d), 111.9
(d), 111.2 (d, 2 C), 109.6 (d), 109.6 (d), 93.3 (d), 78.8 (d), 77.7 (d),
76.3 (t, 2 C), 76.3 (t), 76.1 (t, 2 C), 75.8 (t, 2 C), 75.5 (t), 73.4 (d),
72.7 (t), 72.5 (t, 2 C), 72.5 (t, 2 C), 72.2 (t), 72.2 (t), 70.5 (d), 64.0
(t); HRMS (FAB) m/z: [M + Na]+ Calcd for C146H118O26Na
2309.7809, found 2309.7791.
24
afford 17 (398 mg, 73% yield for 2 steps) as a colorless oil: [α]D
−1.1 (c 0.455, CHCl3); IR 3088, 3063, 3032, 2933, 2873, 1760, 1728,
1589, 1519, 1497, 1482, 1455, 1428, 1412, 1368, 1332, 1249, 1214,
1201, 1178, 1150, 1093, 1076, 1003, 970, 909, 832, 750, 696; 1H NMR
7.61−6.87 (m, 53 H), 6.28 (d, J = 7.6 Hz, 1 H), 5.91 (dd, J = 9.6, 9.6
Hz, 1 H), 5.69 (s, 1 H), 5.34−5.30 (m, 3 H), 5.23−5.10 (m, 8 H),
5.00−4.92 (m, 6 H), 4.71 (d, J = 10.5 Hz, 1 H), 4.62 (d, J = 10.6 Hz, 1
H), 4.49 (dd, J = 10.3, 4.6 Hz, 1 H), 4.22 (dd, J = 9.6, 9.6 Hz, 1 H),
4.14 (ddd, J = 9.6, 9.6, 4.6 Hz, 1 H), 3.98 (dd, J = 10.3, 9.6 Hz, 1 H),
3.75 (s, 3 H); 13C NMR 168.7 (s), 166.7 (s), 165.7 (s), 161.1 (s),
153.8 (s), 153.6 (s), 153.6 (s, 2 C), 153.3 (s), 153.2 (s), 145.2 (s),
145.1 (s), 143.6 (s), 138.7 (s), 138.7 (s), 138.6 (s), 138.5 (s), 138.4
(s), 137.8 (s, 3 C), 137.5 (s), 130.6 (s), 130.0 (s), 129.8 (s), 129.5−
128.5 (overlapping 47 doublets and 1 singlet: 26 peaks were
observed), 125.6 (s), 122.6 (s), 114.2 (d, 2 C), 109.9 (d, 2 C),
108.1 (d), 107.8 (d), 102.5 (d), 97.4 (d), 79.4 (d), 77.4 (d), 76.1 (t, 2
C), 75.9 (t), 75.9 (t), 75.5 (t), 71.8−71.7 (overlapping 4 triplets and 1
Cuspinin (2). A mixture of 14 (76.5 mg, 33.4 μmol) and Pd on
carbon (10 wt %, 28.8 mg) in THF (0.7 mL) and MeOH (0.7 mL)
was stirred for 1.5 h at rt under H2 atmosphere. The mixture was
filtered through a cotton-Celite pad to remove Pd/C. The
concentrated filtrate was purified by Avicel cellulose (Funakoshi)
CC with 2% AcOH, followed by purification on MCI-gel CHP 20P
chromatography. Elution with H2O containing increasing proportions
of MeOH gave 2 (22.4 mg, 72% yield) as a gray amorphous powder.
1
The H and 13C NMR spectra were identical to those of repurified
F
dx.doi.org/10.1021/jo400562k | J. Org. Chem. XXXX, XXX, XXX−XXX