Synthesis and ¹³C‐NMR Spectroscopy of Methylated beta‐Cyclodextrins

Abstract

The methylated analogues of P-cyclodextrin dissolve in cold water 10 -20 times better than P-cyclodextrin itself, however, quite unusually on heating they crystallize from the solution. The structure of heptakis-(2,6-di-O-methyl)and heptakis-(2,3,6-tri-O-methyl)-Pcyclodextrin was proved by gas-liquid chromatographic and 'H-NMR and ' T -N M R spectroscopic investigations. The corresponding model compounds were synthetized and, according to 13C-NMR spectroscopic investigations, a part of the so far published N M R assignations have to be corrected.Synthese und "-C-NMR-Spektroskopie von methylierten 0-Cyclodextrinen. Die methylierten Derivate des P-Cyclodextrins losen sich im kalten Wasser 10-20 ma1 besser als das P-Cyclodcxtrin selbst. In warmem Wasser sind sie schwer loslich. Die Struktur des Heptakis-(2,6-di-O-methyl)-und Heptakis-(2,3,6-tri-O-methyl)-P-cyclodextrins wurde durch GLC-, 'H-NMRund 13C-NMR-Untersuchungen bewiesen. Auf Grund der '3C-NMR-spektroskopischen Untersuchungen der synthetisierten Modellverbindungen und der methylierten P-Cyclodextrinderivate wurden einige publizierte I3C-Daten korrigiert.

Chiral capillary electrophoresis: Facts and fiction on the reproducibility of resolution with randomly substituted cyclodextrins

“…After drying on MgSO 4 , the chloroform layer was evaporated until dryness. The residue was washed with a mixture of diethyl ether/n-pentane (1:1); mp, 154-1607C; yield, 81% [28][29][30]. The so obtained randomly methylated CDs were fractionated by flash silica gel column (ICN, Costa Mesa, CA, USA; 0.032-0.063 mm grain size) chromatography applying a gradient of ethyl acetate and methanol 1:0-1:1.…”

An NMR tool for cyclodextrin selection in enantiomeric resolution by high‐performance liquid chromatography

“…The permethylated CDs were obtained according to a procedure described in the literature. 9 The CDs were lyophilized prior to the preparation of solutions for NMR spectroscopy. Racemic and pure substrates were synthesized in our laboratory as described below.…”

“…and the corresponding alkyl halide followed by regioselective reduction with NaBH 4 (Scheme 2) and the native CDs were permethylated with MeI. 9 All compounds were characterized by mass spectrometry (MS), 1 H and 13 C NMR spectral data and compared with data in the literature. 10 The enantiomerically pure compounds C -1 and C -3 were obtained by bioreductions of the corresponding ketones (Scheme 2).…”

Physicochemical Characterization of Different Batches of Ethylated β-Cyclodextrins

“…We then used combined 1 H and 13 C NMR spectrometry analysis, which is a powerful technique, to furnish the number of nonequivalent protons and carbon atoms. Furthermore, the NMR analysis results give a stronger argument for the assignment of the substituted groups, and NMR has already been successfully used by Szejtli 17 and Hirayama 18 to elucidate CD derivative structures. DS by NMRsThe NMR spectra of Et--CD in CDCl 3 are shown in Figure 2.…”

“…17 Indeed, NMR allows the assignment of derivatization positions. 18,19 Although extensive work has been undertaken to characterize the properties and the applications of the -CD derivatives, and especially of the methylated and hydroxypropylated -CD, 20 little work has been done on ethylated--CD (Et--CD). [21][22][23][24] It has been shown that these Et-CDs can sustain the release of water-soluble drugs following subcutaneous 25 or oral administration.…”