Ortega-Caballero and Bols
657
Benzyl 2A–F,3A–F,6B,6C,6E,6F-hexadecakis-O-benzyl-␣-
72.6, 72.5, 72.4, 72.3, 72.1, 72.0, 71.7, 71.6, 71.4, 71.3,
71.2, 71.0, 70.8, 70.6, 70.4, 70.2, 70.1, 69.9, 69.5, 69.2,
68.9, 68.8, 63.0 (CH2, CH), 60.4 (CH(OH)CN). MALDI-
TOF-MS m/z calcd. for C149H152O31NNa: 2474.0246; found:
2474.316 [M]+.
cyclodextrin-6D-propenoate (12)
TBAF (0.12 mL, 0.12 mmol) was added to a solution of
11 (102 mg, 0.04 mmol) in anhydrous THF (1.2 mL) at
0 °C. The reaction mixture was stirred at 0 °C for 6 h. Aque-
ous NH4Cl was added and the mixture was diluted with
ether (50 mL) and washed successively with water (2 ×
25 mL) and brine (25mL). The organic layer was dried
(MgSO4), filtered, and the organic solvent was removed in
vacuo. The residue was purified by chromatography (eluent
gradient, EtOAc–pentane, 2:7) to afford 12 (73 mg, 75%) as
white foam. [α]D +36.6° (c 1.0, CH3Cl). IR (KBr, cm–1):
3488 (OH), 3030 (C=C), 2924, 1722 (CO2Bn), 1496, 1453,
6D-C-Cyano-␣-cyclodextrin-6A-carboxylic acid (1)
Compound 10 (130 mg, 0.05 mmol) was dissolved in a
mixture of MeOH–EtOAc (1:1, 5 mL). Then Pd/C (13 mg)
and TFA (cat) were added and the mixture was stirred over-
night under a hydrogen atmosphere. Filtration over Celite
and evaporation of the solvent gave 1 (54 mg, 100%) as a
white solid. [α]D +67.2° (c 0.5, H2O). IR (KBr, cm–1): 3423,
2942, 2246 (CN), 1679 (COOH), 1437, 1205, 1151, 1034.
1H NMR (400 MHz, D2O) δ: 5.14–5.07 (m, 6H, H-1), 4.02–
3.63 (m, 40H), 3.32 (m, 1H). 13C NMR (100 MHz, D2O) δ:
163.3 (CO), 163.0 (CO), 119.0 (CN), 101.8 (C-1), 101.7 (C-
1), 101.6 (C-1), 101.5 (C-1), 101.4 (C-1), 101.3 (C-1), 100.7
(C-1), 82.0, 81.7, 81.6, 81.5, 81.4, 81.3, 81.2, 80.9, 74.8,
73.1, 73.0, 72.9, 72.7, 72.4, 72.2, 72.1, 71.9, 71.7, 71.6,
71.5, 71.3, 65.4, 60.7, 60.3, 60.0, 59.7, 68.8, 63.0 (CH, CH2,
CH(OH)CN). MALDI-TOF-MS m/z calcd. for C37H57O31NNa:
1034.2812; found: 1034.127 [M]+.
1354, 1094, 1039. 1H NMR (400 MHz, CDCl3) δ: 7.25–6.98
3
(m, 86H, aromatic-H and CH=), 6.00 (d, 1H, Jtrans
=
3
15.6 Hz, =CHCO2Bn), 5.40 (d, 1H, J1,2 = 3.6 Hz, H-1),
3
5.29 (d, 1H, 2J = 10.4 Hz, CHPh), 5.28 (d, 1H, J1,2
=
2
4.0 Hz, H-1), 5.20–5.13 (m, 3H), 5.06 (d, 1H, J = 10.8 Hz,
CHPh), 4.92 (s, 2H), 4.90 (d, 1H, 3J1,2 = 3.0 Hz, H-1), 4.84–
4.69 (m, 11H), 4.64 (d, 1H, 3J1,2 = 3.2 Hz, H-1), 4.58 (t, 2H,
3
2J = 11.2 Hz), 4.46 (d, 1H, J1,2 = 4.0 Hz, H-1), 4.43 (d, 1H,
3J1,2 = 4.0 Hz, H-1), 4.39–4.20 (m, 17H), 4.15–3.95 (m,
13H), 3.89–3.66 (m, 13H), 3.61–3.57 (m, 2H), 3.50–3.33
3
3
(m, 10H), 3.31 (dd, 1H, J1,2 = 3.2 Hz, J2,3 = 9.6 Hz, H-2),
3
3
3.25 (dd, 1H, J1,2 = 3.2 Hz, J2,3 = 9.6 Hz, H-2), 2.39 (bs,
1H, OH). 13C NMR (100 MHz, CDCl3) δ: 165.8 (CO), 145.8
(CH=), 139.6–137.9 (Cipso), 135.9 (Cipso-CO2Bn), 128.7–
126.5 (CH aromatic), 122.2 (=CHCO2Bn), 99.3 (C-1), 99.0
(C-1), 98.7 (C-1), 98.3 (C-1), 98.2 (C-1), 97.5 (C-1), 82.5,
81.6, 81.4, 81.3, 81.2, 80.6, 80.1, 79.9, 79.6, 79.5, 79.0,
78.7, 78.3, 76.4, 76.2, 76.1, 75.9, 75.8, 74.8, 74.5, 73.5,
73.4, 73.3, 73.2, 73.1, 73.0, 72.9, 72.5, 72.4, 72.0, 71.9,
71.8, 71.6, 69.4, 69.0, 68.9, 66.3, 61.4 (CH2, CH). MALDI-
TOF-MS m/z calcd. for C157H162O31Na: 2566.0998; found:
2566.760 [M]+.
Benzyl 6A-tert-butyldimethylsilyl-2A–F,3A–F,6B,6C,6E,6F-
hexadecakis-O-benzyl-␣-cyclodextrin-6D-propenoate (11)
To a solution of BnO2CCH2PPhBr (496 mg, 1.01 mmol)
in anhydr. THF (13 mL) was added dropwise n-BuLi
(0.6 mL, 0.96 mmol) and the mixture was stirred at room
temperature for 1 h. The reaction mixture was cooled to
–40 °C and a solution of 4 (850 mg, 0.34 mmol) in anhydr.
THF (13 mL) was added. The mixture was stirred at –40 °C
for 30 min and was then allowed to reach room temperature.
Ether (200 mL) was added and the mixture was washed with
aq. NH4Cl (150 mL), water (2 × 100 mL), and brine
(100 mL). The organic layer was dried (MgSO4), filtered,
and the organic solvent was removed in vacuo. The residue
was purified by chromatography (eluent gradient, EtOAc–
pentane, 2:11) to afford 11 (625 mg, 70%) as white foam.
[α]D +42.6° (c 1.0, CH3Cl). IR (KBr, cm–1): 3030 (C=C),
2926, 1720 (CO2Bn), 1496, 1453, 1360, 1094, 1027. 1H
Benzyl 6A-C-cyano-2A–F,3A–F,6B,6C,6E,6F-hexadecakis-O-
benzyl-␣-cyclodextrin-6D-propenoate (13)
To a solution of 12 (246 mg, 0.10 mmol) in Et2O (3.5 mL)
and MeOH (6 mL) were added KCN (189 mg, 2.91 mmol)
and NH4Cl (259 mg, 4.85 mmol) in water (11.5 mL). The
reaction mixture was stirred overnight at room temperature.
After that, the organic solvent was removed and the aqueous
phase was extracted with CH2Cl2. The organic layer was
washed with water, dried (MgSO4), filtered, and the organic
solvent was removed in vacuo. The residue was purified by
chromatography (eluent gradient, EtOAc–pentane, 1:4 →
2:7) to afford 13 (87 mg, 35%) as white foam. [α]D +47.3°
(c 0.8, CH3Cl). IR (KBr, cm–1): 3030 (C=C), 2924, 2246
(CN), 1721 (CO2Bn), 1496, 1454, 1355, 1096, 1040. 1H
3
NMR (400 MHz, CDCl3) δ: 7.50 (dd, 1H, J4,5 = 4.0 Hz,
3Jtrans = 15.6 Hz, CH=), 7.44–7.16 (m, 85H, aromatic-H),
3
6.07 (d, 1H, Jtrans = 15.6 Hz, =CHCO2Bn), 5.42 (d, 1H,
2
3J1,2 = 3.2 Hz, H-1), 5.34 (d, 1H, J = 10.8 Hz, CHPh),
3
5.29–5.10 (m, 10H), 5.24 (d, 1H, J1,2 = 3.2 Hz, H-1), 5.02
3
(d, 1H, J1,2 = 3.2 Hz, H-1), 4.98–4.87 (m, 8H), 4.65–4.40
(m, 23H), 4.28–4.11 (m, 18H), 4.08–3.95 (m, 6H), 3.87 (bd,
2H,3J = 8.0 Hz), 3.71–3.59 (m, 7H), 3.57–3.47 (m, 4H),
3.45–3.37 (m, 3H), 0.91 (s, 9H, SiC(CH3)3), 0.00 (s, 6H,
SiCH3). 13C NMR (100 MHz, CDCl3) δ: 165.9 (CO), 145.8
(CH=), 139.5–137.9 (Cipso), 136.0 (Cipso-CO2Bn), 128.7–
127.1 (CH aromatic), 122.0 (=CHCO2Bn), 99.2 (C-1), 99.0
(C-1), 98.5 (C-1), 98.2 (2 × C-1), 98.1 (C-1), 84.5, 81.4,
81.3, 81.1, 80.9, 80.8, 80.1, 79.7, 79.6, 79.2, 78.7, 78.6,
78.4, 78.0, 76.0, 75.9, 75.5, 75.3, 73.7, 73.4, 73.2, 72.9,
72.8, 72.7, 72.6, 72.5, 72.1, 71.9, 71.5, 71.3, 69.5, 69.4,
68.9, 68.5, 66.3, 62.3, 60.5 (CH2, CH). MALDI-TOF-MS
3
NMR (400 MHz, CDCl3) δ: 7.38 (dd, 1H, J4,5 = 4.8 Hz,
3Jtrans = 15.6 Hz, CH=), 7.33–7.09 (m, 85H, aromatic-H),
3
6.17 (d, 1H, Jtrans = 15.6 Hz, =CHCO2Bn), 5.30 (bd, 1H,
2
3J = 7.6 Hz), 5.24 (d, 1H, J = 10.4 Hz, CH2Ph), 5.22 (d,
3
2
1H, J1,2 = 3.6 Hz, H-1), 5.18 (d, 1H, J = 11.2 Hz, CHPh),
3
2
5.16 (d, 1H, J1,2 = 3.6 Hz, H-1), 5.11 (d, 1H, J= 10.8 Hz,
CHPh), 5.08–4.98 (m, 7H), 4.91–4.76 (m, 8H), 4.67–4.57
2
(m, 5H), 4.51–4.39 (m, 15H), 4.35 (d, 1H, J = 12.0 Hz),
2
4.30 (d, 1H, J = 12.4 Hz), 4.18–3.77 (m, 23H), 3.71 (t, 1H,
2
m/z calcd. for
C
163H176O31SiNa: 2680.1863; found:
3J = 9.0 Hz), 3.65 (d, 1H, J = 10.8 Hz), 3.58–3.47 (m, 8H),
2680.434 [M]+.
3.45 (dd, 1H, J1,2 = 3.2 Hz, J2,3 = 9.6 Hz, H-2), 3.41 (dd,
3
3
© 2006 NRC Canada