Y. Himeno et al. / Tetrahedron 65 (2009) 9474–9480
9479
were performed with a SHIMADZU AXIMA-Resonance, with 2,5-
dihydroxybenzoic acid as the matrix. UV absorbance of fractions on
low-pressure RP column chromatography was recorded on a Shi-
madzu UVmini-1240 instrument. IR spectra were recorded on a Jasco
FT IR 200. TLC wasrun onprecoated silica-gelplates (Art5554, Merck)
using 1-propanol/ethyl acetate/water (7:7:5, v/v/v) as the eluent and
visualizing using UV light and/or staining with 0.1% 1,3-naph-
thalenediol in EtOH/water/H2SO4 [200:157:43 (v/v/v)]. Prepacked
ODS column [Merck, LiChroprep RP-18, size C (37ꢀ440 mm)] was
used for low-pressure RP column chromatography. Analytical RP-
147.6, 150.9, 154.7; MS m/z 1610.5499 (MþNa, 1610.5529 calcd for
C63H101N3NaO41S); IR (KBr) 2104 cmꢁ1. Compound 2d: Rf 0.48; tR
146.9 min [24% MeCN in water; flow rate, 1.0 mL/min]; 1H NMR
(300 MHz, Me2SO-d6)
d
1.18–1.23 [18H, 6ꢀCH3], 2.94 (1H), 3.05–
3.80, 3.80–3.90 (1H), 4.00 (2H), 4.26 (2H), 4.33 (1H), 4.51–4.62(6H),
4.82–4.96 [8H, C(1)H], 5.71–5.93 [16H, C(2)OH and C(3)OH], 7.28
(2H, s, aromatic H); 13C NMR (150 MHz, Me2SO-d6)
d 24.1, 24.2, 24.7,
25.2, 25.3, 25.7, 28.9, 30.0, 34.1, 34.4, 51.8, 60.7, 60.8, 69.3, 70.0, 71.3,
73.0, 73.1, 73.2, 73.4, 73.5, 73.6, 73.7, 73.8, 80.6, 81.4, 81.7, 81.9, 83.4,
101.9, 102.1, 102.3, 102.5, 102.6, 103.0, 103.1, 122.2, 124.6, 130.0,
142.9, 147.6, 148.0, 150.9, 154.6; MS m/z 1610.5540 (MþNa,
1610.5529 calcd for C63H101N3NaO41S); IR (KBr) 2104 cmꢁ1. Com-
pound 2e: Rf 0.48; tR 163.9 min [24% MeCN in water; flow rate,
HPLC was carried out using an YMC J’sphere ODS-M80 column (4 mm;
4.6ꢀ250 mm, YMC Inc.). Preparative HPLC was performed using an
YMC-Pack ODS-M80 column (4
YMC-Guard pack ODS-M80 (5
macia Fine Chemicals Sephadex LH-20 was used for gel permeation
chromatography.
m
m; 20ꢀ250 mm, YMC Inc.) with an
mm; 20ꢀ50 mm, YMC Inc.). A Phar-
1.0 mL/min]; 1H NMR (300 MHz, Me2SO-d6)
d 1.18–1.23 [18H,
6ꢀCH3], 2.94 (1H), 3.08–3.79, 3.82 (1H), 4.01 (2H), 4.27 (2H), 4.38–
4.48 (2H), 4.49–4.65 (5H), 4.80–4.98 [8H, C(1)H], 5.70–6.00 [16H,
C(2)OH and C(3)OH], 7.29 (2H, s, aromatic H); 13C NMR (150 MHz,
4.2. Azido-Tips-CDs 2a–2f
Me2SO-d6) d 24.1, 24.2, 24.7, 25.2, 25.3, 25.7, 28.9, 30.0, 34.1, 34.4,
60.6, 60.7, 60.8, 61.0, 70.0, 71.3, 72.9, 73.0, 73.1, 73.2, 73.3, 73.4, 73.5,
73.6, 73.7, 73.8, 80.2, 81.4, 81.5, 81.7, 81.8, 82.0, 83.5, 101.7, 101.9,
102.4, 102.6, 102.7, 103.1, 122.2, 124.6, 129.9, 147.7, 148.0, 150.9,
154.6; MS m/z 1610.5450(MþNa, 1610.5529 calcd for
C63H101N3NaO41S); IR (KBr) 2105 cmꢁ1. Compound 2f: Rf 0.48; tR
234.7 min [24% MeCN in water; flow rate, 1.0 mL/min]; 1H NMR
6-Azido-g
-CD 18 (576 mg, 0.44 mmol) and zinc bromide
(252 mg, 1.1 mmol) were dissolved in dry pyridine (6 mL) cooled in
an ice water bath and reacted with TipsCl (0.343 g, 1.10 mmol) for
40 min. After addition of water (3 mL), the reaction mixture was
concentrated in vacuo and the residue was added to acetone
(180 mL). The precipitate was collected by centrifugation
(3000 rpm, 10 min) and dissolved in 28% aq MeCN (100 mL). The
solution was subjected to low-pressure RP column chromatography
(size C). After elution with 28% aq MeCN (600 mL) followed by
a gradient elution from 28% aq MeCN (2.7 L) to 31% aq MeCN (2.7 L),
a gradient elution from 31% aq MeCN (2.7 L) to 34% aq MeCN (2.7 L)
gave mixtures of 2a–2c (124 mg), 2d and 2e (65 mg), and 2f and 2g
(53 mg). The mixture of 2a–2c was applied to preparative HPLC
using 24% aq MeCN as an eluent, which gave 2a (26.9 mg, 3.9%), 2b
(26.0 mg, 3.8%), and 2c (27.3 mg, 3.9%). The mixture of 2d and 2e
gave 2d (25.5 mg, 3.7%) and 2e (27.6 mg, 4.0%) using 27% aq MeCN
as an eluent. The isomers 2f (15.2 mg, 2.2%) and 2g (19.8 mg, 2.9%)
were obtained, respectively, from the corresponding mixture using
27% aq MeCN. Compound 2a: Rf 0.48; tR 80.2 min [24% MeCN in
water; flow rate, 1.0 mL/min]; 1H NMR (300 MHz, Me2SO-d6)
(300 MHz, Me2SO-d6)
d
1.19–1.23 [18H, 6ꢀCH3], 2.95 (1H), 3.05–
3.96, 3.82 (1H), 4.00 (2H), 4.18–4.45 (4H), 4.48–4.73 (6H), 4.82–5.03
[8H, C(1)H], 5.65–6.10 [16H, C(2)OH and C(3)OH], 7.30 (2H, s, aro-
matic H); 13C NMR (150 MHz, Me2SO-d6)
d 24.1, 24.2, 24.7, 25.2,
25.3, 25.7, 28.9, 30.0, 30.7, 34.1, 34.4, 60.8, 60.9, 70.1, 71.1, 72.7, 72.9,
73.1, 73.2, 73.3, 73.4, 73.6, 73.7, 73.8, 73.9, 81.3, 81.5, 81.7, 81.9, 82.0,
83.5,102.0,102.2, 102.4,102.5,102.6,102.7,102.8, 103.2,122.2,124.6,
129.7, 147.6, 150.9, 151.1, 154.7; MS m/z 1610.5437 (MþNa,
1610.5529 calcd for C63H101N3NaO41S); IR (KBr) 2104 cmꢁ1. Com-
pound 2g: Rf 0.48; tR 246.3 min [24% MeCN in water; flow rate,
1.0 mL/min]; 1H NMR (300 MHz, Me2SO-d6)
d 1.18–1.23 [18H,
6ꢀCH3], 2.94 (1H), 3.08–3.80, 3.88 (1H), 4.03 (2H), 4.08–4.16 (2H),
4.48–4.61 (6H), 4.66 (1H), 4.83–4.89 [8H, C(1)H], 5.70–5.99 [16H,
C(2)OH and C(3)OH], 7.30 (2H, s, aromatic H); 13C NMR (150 MHz,
Me2SO-d6)
d 24.1, 24.2, 24.7, 25.2, 25.7, 28.9, 30.0, 30.7, 34.1, 34.3,
d
1.02–1.32 [18H, 6ꢀCH3], 2.92 (2H), 3.19–3.80, 3.82 (1H), 3.98 (2H),
60.6, 60.7, 60.8, 60.9, 69.9, 71.0, 72.9, 73.1, 73.3, 73.4, 73.6, 73.9, 81.1,
81.3, 81.6, 81.7, 81.8, 81.9, 82.0, 82.2, 82.6, 101.7, 102.4, 102.5, 102.6,
102.7, 102.8, 103.1, 122.2, 124.7, 129.9, 147.6, 147.9, 151.0, 154.6; MS
m/z 1610.5474 (MþNa, 1610.5529 calcd for C63H101N3NaO41S); IR
4.18–4.31 (3H), 4.43–4.62 (6H), 4.78–4.95 [8H, C(1)H], 5.65–5.94
[16H, C(2)OH and C(3)OH], 7.26 (2H, s, aromatic H); 13C NMR
(150 MHz, Me2SO-d6)
d 24.3, 24.7, 25.2, 25.3, 25.7, 28.9, 30.0, 30.7,
32.5, 34.1, 34.4, 60.0, 60.5, 60.6, 60.7, 61.0, 69.9, 71.2, 72.9, 73.0, 73.1,
73.2, 73.4, 73.5, 73.6, 73.8, 80.8, 81.2, 81.5, 82.0, 83.6, 101.7, 102.0,
102.5, 102.8, 103.0, 122.2, 124.6, 129.9, 147.6, 150.9, 154.6; MS m/z
1610.5434 (MþNa, 1610.5529 calcd for C63H101N3NaO41S); IR (KBr)
2104 cmꢁ1. Compound 2b: Rf 0.48; tR 84.4 min [24% MeCN in water;
(KBr) 2105 cmꢁ1
.
4.3. Di-Tips-CDs 3a–3d
-CD (3.86 g, 3.0 mmol) and zinc bromide (1.70 g, 7.5 mmol)
g
flow rate, 1.0 mL/min]; 1H NMR (300 MHz, Me2SO-d6)
d
1.11–1.23
were dissolved in dry pyridine (50 mL) cooled in an ice water bath
and reacted with TipsCl (2.32 g, 7.43 mmol) for 90 min. After ad-
dition of water (5 mL), the reaction mixture was concentrated in
vacuo and the residue was added to acetone (200 mL). The pre-
cipitate was collected by centrifugation (3000 rpm, 10 min) and
dissolved in 45% aq MeCN (100 mL). The solution was subjected to
low-pressure RP column chromatography (size C). After elution
with 45% aq MeCN (600 mL) followed by a gradient elution from
45% aq MeCN (1.5 L) to 65% aq MeCN (1.5 L), a gradient elution from
65% aq MeCN (750 mL) to 75% aq MeCN (750 mL) gave 3a (130 mg,
2.4%), 3b (145 mg, 2.7%), 3c (244 mg, 4.5%), and 3d (110 mg, 2.0%).
Compound 3a: Rf 0.54; tR 19.9 min [gradient, 30–70% MeCN in
water (40 min); flow rate, 1.0 mL/min]; 1H NMR (300 MHz, Me2SO-
[18H, 6ꢀCH3], 2.94 (1H), 3.05–3.80, 3.82 (1H), 4.00 (2H), 4.19–4.30
(3H), 4.43–4.62 (7H), 4.78–4.95 [8H, C(1)H], 5.67–5.93 [16H,
C(2)OH and C(3)OH], 7.29 (2H, s, aromatic H); 13C NMR (150 MHz,
Me2SO-d6)
d 24.1, 24.3, 24.7, 25.2, 25.3, 25.7, 28.9, 30.0, 30.7, 31.6,
34.1, 34.4, 51.9, 60.1, 60.3, 60.7, 60.8, 70.0, 71.2, 73.0, 73.1, 73.2, 73.4,
73.5, 73.6, 73.7, 80.9, 81.5, 81.6, 81.9, 83.3, 101.7, 102.2, 102.5, 102.7,
103.0, 103.1, 122.2, 124.6, 129.9, 147.6, 147.9, 150.9, 154.6; MS m/z
1610.5397 (MþNa, 161.5529 calcd for 63H101N3NaO41S); IR (KBr)
2104 cmꢁ1. Compound 2c: Rf 0.48; tR 88.4 min [24% MeCN in water;
flow rate, 1.0 mL/min]; 1H NMR (300 MHz, Me2SO-d6)
d 1.08–1.30
[18H, 6ꢀCH3], 2.93 (1H), 3.03–3.80, 3.85 (1H), 4.00 (2H), 4.24 (2H),
4.32 (1H), 4.44 (1H), 4.49–4.61 (4H), 4.67 (1H), 4.80–4.99 [8H,
C(1)H], 5.64–6.01 [16H, C(2)OH and C(3)OH], 7.28 (2H, s, aromatic
d6)
d
0.95–1.30 (36H,12ꢀCH3), 2.92 (2H), 2.95–3.75, 3.80–4.05 (6H),
H); 13C NMR (150 MHz, Me2SO-d6)
d
24.1, 24.3, 24.7, 25.2, 25.3, 25.7,
4.06 (2H), 4.15–4.30 (4H), 4.40–4.70 (5H), 4.85–5.00 [8H, C(1)H],
28.9, 29.9, 30.0, 34.1, 34.4, 51.9, 60.0, 60.5, 60.6, 60.7, 61.0, 61.1, 72.9,
73.1, 73.4, 73.5, 73.6, 73.8, 80.9, 81.0, 81.4, 81.5, 81.6, 81.9, 82.2, 83.5,
101.9, 102.4, 102.5, 102.6, 102.8, 103.0, 103.1, 122.2, 124.5, 129.9,
5.60–6.05 [16H, C(2)OH and C(3)OH], 7.24 (4H, s, aromatic H); 13C
NMR (150 MHz, Me2SO-d6)
d 24.1, 25.1, 25.3, 30.0, 34.3, 60.0, 60.3,
60.5, 69.4, 69.8, 72.8, 73.0, 73.1, 73.4, 73.5, 73.6, 73.9, 80.8, 80.9, 81.2,