Cyclodextrin Artificial Glycosidases
3.60–3.49 (m, 28 H), 3.45–3.43 (s, 6 H), 3.43–3.40 (m, 4 H), 3.40–
chromatography (eluent gradient, CH2Cl2/MeOH, 0:1Ǟ24:1), af-
3.37 (m, 7 H), 3.21–3.11 (m, 6 H) ppm. 13C NMR (75 MHz, fording the desired product (43.0 mg, 80%) as a colorless solid.
CD3OD): δ = 120.8 (CN), 100.4 (2ϫC-1), 100.0 (2ϫC-1), 99.9 (C-
TLC indicated that there were about equal amounts of the cya-
1), 99.8 (C-1), 83.4, 83.0, 83.0, 83.0, 83.0, 82.9, 82.9, 82.8, 82.7, nohydrin (S)- and (R)-isomers; the bulk purified product was race-
82.6, 82.4, 82.1, 81.9, 81.5, 74.0, 73.3, 72.9, 72.8, 72.6, 72.5, 72.2,
72.1, 72.0, 71.8, 62.0, 61.9, 61.9, 61.7, 61.5, 61.0, 59.3, 59.3, 59.1,
59.1, 58.9, 58.7, 58.5, 58.3, 58.1, 58.0 ppm. MALDI-TOF-MS: m/z
calcd. for C54H93NO30Na: 1258.568, found 1258.666.
mic, but a few fractions containing only single (S)- or (R)-isomer
were successfully isolated.
(R)-isomer (most apolar): [α]2D0 = +141.0 (c = 0.2, MeOH). IR
(KBr): ν = 3436, 3030, 2928, 1724, 1630, 1604, 1496, 1454, 1364,
˜
6A,6D-Di-C-cyano-2A–F,3A–F,6B,C,E,F-hexadecakis-O-methyl-α-cyclo-
1274, 1207, 1094, 1041 cm–1. 1H NMR (300 MHz, CD3OD): δ =
5.24 (d, J1,2 = 3.3 Hz, 1 H, 1-H), 5.20 (d, J1,2 = 2.4 Hz, 1 H, 1-H),
5.18–5.09 (m, 5 H, 1-H), 4.44–3.66 (m, 11 H), 3.66–3.60 (m, 21 H,
OMe), 3.60–3.52 (m, 9 H), 3.52–3.47 (m, 21 H, OMe), 3.44–3.34
(m, 16 H), 3.33–3.27 (m, 15 H), 3.23 (dd, J1,2 = 3.3, J2,3 = 9.0 Hz,
2 H, 2-H), 3.19–3.11 (m, 6 H) ppm. MALDI-TOF-MS: m/z calcd.
for C63H109NO35Na: 1462.668, found 1462.159.
dextrin (21): HCl (2.0 , 0.8 mL) was added to a mixture of 6A,D
-
dioxo-2A–F,3A–F,6B–C,E–F-hexadecakis-O-methyl-α-cyclodextrin (20)
(14.3 mg, 0.012 mmol) and potassium cyanide (117 mg,
1.798 mmol, 150 equiv.) in water (0.2 mL) at 5 °C. The reaction
mixture was stirred overnight at room temperature. Reaction pro-
gress was checked by TLC (eluent: 6% MeOH in CH2Cl2). The
aqueous layer was extracted with CH2Cl2 (5ϫ10 mL), dried
(MgSO4), filtered, and concentrated in vacuo. The residue was
purified by flash column chromatography (eluent gradient, CH2Cl2/
MeOH, 0:1Ǟ97:3), affording the desired product (14.3 mg, 96%)
as a colorless solid. All three 6A,6D stereogenic position isomers
were present.
(S)-isomer (most polar): [α]2D0 = +127.3 (c = 0.2, MeOH). IR (KBr):
1
ν = 3435, 2928, 1618, 1490, 1083, 1039 cm–1. H NMR (300 MHz,
˜
CD3OD): δ = 5.49–5.46 (m, 1 H, 1-H), 5.25 (d, J1,2 = 3.3 Hz, 1 H,
1-H), 5.19 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 5.17–5.12 (m, 3 H, 1-H),
5.10 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 3.95–3.66 (m, 9 H), 3.66–3.61 (m,
21 H, OMe), 3.61–3.53 (m, 8 H), 3.53–3.45 (m, 21 H, OMe), 3.43–
3.33 (m, 20 H), 3.33–3.27 (m, 14 H), 3.20–3.11 (m, 8 H) ppm.
MALDI-TOF-MS: m/z calcd. for C63H109NO35Na: 1462.668,
found 1462.358.
(R,R)-isomer (most apolar): [α]2D0 = +49.0 (c = 0.17, MeOH). IR
(KBr): ν = 3436, 2928, 2858, 1636, 1629, 1487, 1364, 1163, 1096,
˜
1041 cm–1. 1H NMR (300 MHz, CD3OD): δ = 5.34 (d, J1,2
=
2.1 Hz, 1 H, 1-H), 5.17 (d, J1,2 = 2.7 Hz, 1 H, 1-H), 5.09–4.98 (m,
4 H, 1-H), 4.03–3.67 (m, 13 H), 3.67–3.58 (m, 18 H), 3.58–3.44 (m,
27 H), 3.44–3.35 (m, 15 H), 3.23–3.05 (m, 9 H) ppm. MALDI-
TOF-MS: m/z calcd. for C54H90N2O30Na: 1269.548, found
1269.851.
(R,S) racemic mixture: 13C NMR (75 MHz, CD3OD): δ = 120.9
(CN), 119.2 (CN), 100.4 (C-1), 99.9–99.3 (C-1), 83.6, 83.5, 83.5,
83.5, 83.4, 83.2, 83.2, 83.1, 83.1, 82.9, 82.9, 82.2, 81.4, 81.1, 81.0,
80.8, 80.8, 80.6, 80.6, 80.5, 80.4, 74.1, 74.1, 73.4, 72.8, 72.8, 72.7,
72.7, 72.4, 72.4, 72.3, 72.3, 72.0, 63.3, 62.2, 62.0, 61.9, 61.9, 61.8,
61.8, 61.7, 61.2, 59.6, 59.6, 59.4, 59.4, 59.3, 59.2, 59.1, 59.1, 59.0,
58.9, 58.6 ppm. MALDI-TOF-MS: m/z calcd. for C63H109NO35Na:
1462.668, found 1462.246.
(R,S) = (S,R)-isomer [and small amounts of (S,S)-isomer]: [α]2D0
=
+59.6 (c = 0.5, MeOH). IR (KBr): ν = 3436, 2918, 2851, 1630,
˜
1490, 1385, 1262, 1095, 1029 cm–1. 1H NMR (300 MHz, CD3OD):
δ = 5.56 (d, J1,2 = 1.5 Hz, 0.5 H, 1-H), 5.41 (d, J1,2 = 1.8 Hz, 0.5
H, 1-H), 5.23–5.17 (m, 2 H, 1-H), 5.11 (d, J1,2 = 3.6 Hz, 0.5 H, 1-
H), 5.09–5.03 (m, 2.5 H, 1-H), 4.25–3.70 (m, 9 H), 3.70–3.59 (m,
24 H), 3.59–3.48 (m, 26 H), 3.48–3.37 (m, 15 H), 3.27–3.12 (m, 8
H) ppm. 13C NMR (75 MHz, CD3OD): δ = 100.7 (C-1), 100.7 (C-
1), 100.1 (C-1), 84.6, 83.2, 83.1, 83.0, 82.9, 82.8, 82.7, 81.9, 74.2,
73.6, 73.0, 72.9, 72.3, 72.2, 62.2, 62.2, 61.3, 59.5, 59.5, 59.2, 58.7
ppm. MALDI-TOF-MS: m/z calcd. for C54H90N2O30Na: 1269.548,
found 1269.528.
6A,6D-Di-C-cyano-2A–G,3A–G,6B,C,E–G-nonadecakis-O-methyl-β-cyclo-
dextrin (25): HCl (1.0 , 2.3 mL) was added to a mixture of 6A,6D-
dioxo-2A–G,3A–G,6B–C,E–G-nonadecakis-O-methyl-β-cyclodextrin
(24) (21 mg, 0.015 mmol) and potassium cyanide (147 mg,
2.255 mmol, 150 equiv.) at 5 °C. The reaction mixture was stirred
overnight at room temperature. Reaction progress was checked by
TLC (eluent: 6% MeOH in CH2Cl2). The aqueous layer was ex-
tracted with CH2Cl2, dried (MgSO4), filtered, and concentrated in
vacuo along with silica gel. The residue was purified by flash
column chromatography (eluent gradient, CH2Cl2/MeOH,
0:1Ǟ24:1), affording the desired product (18.5 mg, 85%) as a col-
orless solid. All 4 possible 6A,6D-disubstituted cyanohydrin CD iso-
mers were present. Whilst the (S,S)-isomer was plentiful and the
major isomer, only trace amounts of the (R,R)-isomer were de-
tected.
(S,S)-isomer (most polar): [α]2D0 = +55.2 (c = 0.5, MeOH). IR
(KBr): ν = 3435, 2962, 2927, 2858, 1629, 1490, 1262, 1083, 1028
˜
cm–1. 1H NMR (300 MHz, CD3OD): δ = 5.62 (br. s, 1 H, 1-H),
5.23–5.14 (m, 2 H, 1-H), 5.10 (d, J1,2 = 3.9 Hz, 1 H, 1-H), 5.08–
5.02 (m, 2 H, 1-H), 4.34 (d, J = 11.1 Hz, 0.5 H), 4.09–3.80 (m, 5.5
H), 3.80–3.60 (m, 25 H), 3.60–3.47 (m, 27 H), 3.47–3.37 (m, 15 H),
3.25–3.09 (m, 9 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 121.1
(2ϫCN), 101.0 (2ϫC-1), 100.4 (2ϫC-1), 99.7 (2ϫC-1), 83.7,
83.3, 83.1, 83.1, 82.7, 82.6, 82.5, 82.2, 82.1, 74.4, 73.8, 72.4, 72.4,
71.7, 62.4, 62.3, 61.5, 61.3, 59.9, 59.8, 59.5, 58.7, 57.7 ppm.
MALDI-TOF-MS: m/z calcd. for C54H90N2O30Na: 1269.548,
found 1269.348.
(R,S)- and (S,R)-isomer mixture: IR (KBr): ν = 3400, 2956, 1508,
˜
1491, 1420, 1385, 1162, 1142, 1108, 1035 cm–1. 1H NMR
(300 MHz, CD3OD): δ = 5.55–5.53 (m, 0.5 H, 1-H), 5.51–5.49 (m,
0.5 H, 1-H), 5.29–5.04 (m, 6 H, 1-H), 4.20–3.70 (m, 11 H), 3.69–
3.59 (m, 26 H), 3.59–3.44 (m, 34 H), 3.44–3.34 (m, 18 H), 3.26–3.12
(m, 8 H) ppm. MALDI-TOF-MS: m/z calcd. for C63H106N2O35Na:
1473.647, found 1473.4630.
6A-C-Cyano-2A–G,3A–G,6B–G-eiocosakis-O-methyl-β-cyclodextrin (23):
HCl (2.0 , 2.0 mL) was added to a mixture of 2A–G,3A–G,6B–G
-
eiocosakis-O-methyl-6A-oxo-β-cyclodextrin
(22)
(53 mg,
(S,S)-isomer (most polar): [α]2D0 = +138.0 (c = 1.0, MeOH). IR
0.0375 mmol) and potassium cyanide (244 mg, 3.75 mmol,
100 equiv.) at 5 °C. The reaction mixture was stirred overnight at
room temperature. Reaction progress was checked by TLC (eluent:
6% MeOH in CH2Cl2) and MALDI-TOF-MS. The aqueous layer
was extracted with CH2Cl2 (5ϫ5 mL), dried (MgSO4), filtered, and
concentrated in vacuo. The residue was purified by flash column
(KBr): ν = 3434, 2927, 2855, 1654, 1636, 1630, 1384, 1033 cm–1.
˜
1H NMR (300 MHz, CD3OD): δ = 5.58 (br. s, 1 H, 1-H), 5.30 (d,
J1,2 = 3.6 Hz, 1 H, 1-H), 5.28 (d, J1,2 = 2.7 Hz, 1 H, 1-H), 5.25 (d,
J1,2 = 4.8 Hz, 1 H, 1-H), 5.15 (d, J1,2 = 3.6 Hz, 1 H, 1-H), 5.10 (d,
J1,2 = 3.3 Hz, 2 H, 1-H), 4.43–4.21 (m, 2 H), 3.99–3.73 (m, 14 H),
3.73–3.61 (m, 26 H), 3.61–3.48 (m, 32 H), 3.47–3.37 (m, 16 H),
Eur. J. Org. Chem. 2010, 3487–3500
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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