Impact of Substituent Position in Monosubstituted -Cyclodextrins on
Enantioselectivity in Capillary Electrophoresis
Michal Řezanka, Pavel Řezanka, David Sýkora*, Jindřich Jindřich, Vladimír Král
Supporting Information
Experimental – additional supporiting data
1. Equipment
NMR spectra were recorded with a Bruker Avance III (600 MHz) (1H at 600.17 MHz, 13C NMR at
150.04 MHz) with solutions in deuterated solvents and referenced to residual solvent peak.
Chemical shifts are given in δ-scale, coupling constants J in Hz. Numbering of atoms for NMR
spectra transcription was done according to Fig. S1. Position numbers of glucose unit bearing an
alkyl substituent are tagged with “I” symbol where the assignment is unambiguous. Positions
corresponding to all other glucose signals are numbered indiscriminately. Position numbers of
atoms in alkyl substituent are tagged with “ ´ ” symbol. The assignment of the 1H and 13C signals
was based on 2D NMR techniques (1H-1H COSY, HSQC, HMBC) and APT.
Fig. S1. Numbering of atoms in -cyclodextrin derivatives
2. Synthesis of monosubstituted carboxymethyl derivatives of -CD
2I-O-, 3I-O-, and 6I-O-carboxymethyl--cyclodextrins (2I-O-, 3I-O-, and 6I-O-CMACD) were
synthesized by Zemplen deacetylation of previously described per-O-acetyl-2I-O-, 3I-O-, and 6I-Ocarboxymethyl--cyclodextrins (per-Ac-2I-O-, 3I-O-, and 6I-O-CMACD) by Jindrich’s group
[Řezanka, M., Jindřich, J., Carbohydr. Res. 2011, 15, 2374-2379.] (Scheme S1). The purity of
CMACD was determined by NMR and for all derivatives was > 95 %.
1
AcO
O
O
AcO
HO
O
HO
COOH
O
O
OAc
a
OAc
O
96 %
O
OAc
5
Per-Ac-2I-O-CMACD
AcO
HOOC
O
COOH
O
OH
OH
O
OH
5
2I-O-CMACD
O
HO
O
O
HOOC
O
O
O
AcO
HO
OAc
OH
a
OAc
O
99 %
O
OAc
5
Per-Ac-3I-O-CMACD
HOOC
OH
O
OH
5
3I-O-CMACD
O
HOOC
O
O
O
O
HO
O
AcO
O
AcO
OAc
HO
a
OAc
O
97 %
OAc
5
Per-Ac-6I-O-CMACD
O
OH
OH
O
OH
5
6I-O-CMACD
O
a = CH3ONa/CH3OH
Scheme S1. Preparation of monosubstituted carboxymethyl--cyclodextrins
2I-O-Carboxymethyl--cyclodextrin (2I-O-CMACD). A solution of MeONa in MeOH (20 mL,
0.1 mol/L, 2.0 mmol) was added to per-Ac-2I-O-CMACD (851 mg, 0.49 mmol) under Ar
atmosphere. The reaction mixture was stirred for 1 h, quenched by addition of water (15 mL). The
reaction mixture was evaporated and the residue was dissolved in water (10 mL). The solution was
stirred with DOWEX 50Wx2 in H+ form (10 g) for 15 minutes and DOWEX was filtered out.
Evaporation of the solution afforded 482 mg (96 %) of the title compound as a white powder.
Spectral characteristics were in agreement with the published data [Hanessian, S., Benalil, A.,
Laferriere, C., J. Org. Chem. 1995, 60, 4786-4797].
3I-O-Carboxymethyl--cyclodextrin (3I-O-CMACD). A solution of MeONa in MeOH (16 mL,
0.1 mol/L, 1.6 mmol) was added to per-Ac-3I-O-CMACD (704 mg, 0.40 mmol) under Ar
atmosphere. The reaction mixture was stirred for 1 h, quenched by addition of water (10 mL). The
reaction mixture was evaporated and the residue was dissolved in water (8 mL). The solution was
stirred with DOWEX 50Wx2 in H+ form (8 g) for 15 minutes and DOWEX was filtered out.
Evaporation of the solution afforded 410 mg (99 %) of the title compound as a white powder: 1H
NMR (600 MHz, D2O): δ 5.15–5.01 (m, 6 H, 6 × H-1), 4.71 (d, 1 H, Jgem 16.9 Hz, H-1´), 4.48 (d, 1
2
H, Jgem 16.9 Hz, H-1´), 4.06–3.53 (m, 36 H, 6 × H-2, 6 × H-3, 6 × H-4, 6 × H-5, 12 × H-6) ppm. 13C
NMR (151 MHz, D2O): δ 176.91 (C-2´), 103.58 (C-1), 103.39 (C-1), 103.36 (C-1), 103.30 (C-1),
103.28 (C-1), 103.23 (C-1), 83.54–73.04 (6 × C-2, 6 × C-3, 6 × C-4, 6 × C-5), 71.15 (C-1´), 62.48–
61.96 (6 × C-6) ppm. MS (ESI): m/z = 1029.2 [M - H]-.
6I-O-Carboxymethyl--cyclodextrin (6I-O-CMACD). A solution of MeONa in MeOH (4.5 mL,
0.1 mol/L, 0.45 mmol) was added to per-Ac-6I-O-CMACD (192 mg, 0.11 mmol) under Ar
atmosphere. The reaction mixture was stirred for 1 h, quenched by addition of water (4 mL). The
reaction mixture was evaporated and the residue was dissolved in water (5 mL). The solution was
stirred with DOWEX 50Wx2 in H+ form (2 g) for 15 minutes and DOWEX was filtered out.
Evaporation of the solution afforded 110 mg (97 %) of the title compound as a white powder: 1H
NMR (600 MHz, D2O): δ 5.09–5.04 (m, 6 H, 6 × H-1), 4.26 (d, 1 H, Jgem 16.8 Hz, H-1´), 4.20 (d, 1
H, Jgem 16.8 Hz, H-1´), 4.02–3.56 (m, 36 H, 6 × H-2, 6 × H-3, 6 × H-4, 6 × H-5, 12 × H-6) ppm. 13C
NMR (151 MHz, D2O): δ 175.58 (C-2´), 102.96–102.51 (6 × C-1), 82.84–72.07 (6 × C-2, 6 × C-3,
6 × C-4, 6 × C-5), 71.21 (C-6I), 69.52 (C-1´), 62.48–61.96 (5 × C-6) ppm. MS (ESI): m/z = 1029.2
[M - H]-.
3