Properties and the Inclusion Behavior of 6-O-.ALPHA.-D-Galactosyl- and 6-O-.ALPHA.-D-Mannosyl-cyclodextrins.

Abstract

The novel heterogeneous branched cyclodextrins (CDs), 6-O-alpha-D- galactosyl-alpha, -beta, and -gamma CDs (Gal-alpha, -beta, and -gamma CDs) and 6-O-alpha-D-mannosyl-alpha, -beta, and -gamma CDs (Man-alpha, -beta, and -gamma CDs) dissolved sufficiently in water and in 10-50% (v/v) methanol aqueous solutions, as did the homogeneous branched CDs, 6-O-alpha-D-glucosyl-alpha, -beta, and -gamma CDs (Glc-alpha, -beta, and -gamma CDs). The solubilities of heterogeneous branched CDs were higher than those of each parent non-branched CDs. The hemolytic activities of heterogeneous and homogeneous branched CDs were lower than those of each parent non-branched CDs and the hemolytic activity became weaker in the order of non-branched CD > Man-CD > Glc-CD > Gal-CD in each series of alpha, beta, and gamma CD. AL type solubility-phase diagrams were displayed in the formation of inclusion complexes of the guest compounds of small size (methyl benzoate, estriol, and dexamethasone) with Gal-, Man-, and Glc-CDs, and marked differences among the three kinds of branched CDs could not be detected. However, solubility-phase diagrams between these branched CDs and the insoluble guest compounds of large cyclic structure (cyclosporin A, tacrolimus, and amphotericin B) showed AP type, and the improvement of water solubilities of these guest compounds with three kinds of branched CDs was enhanced in the order of Man-CDs > Glc-CDs > Gal-CDs.

Preparation and Characterization of Branched β-Cyclodextrins Having α-L-Fucopyranose and a Study of Their Functions

“…As a result, the L-Fuc groups were linked to CD only by a -(1!6)-linkage. Therefore, to obtain an -(1!6)-linkage, labile 2,3,4-tri-O-benzyl-L-fucopyranosyl trichloroacetimidate (21) [15][16][17] and mono-fucosylated CD derivatives. The product containing 15 and mono-fucosylated CD X, 16 and mono-fucosylated CD Y, or 17 and mono-fucosylated CD Z was fractionated several fractions by centrifugal chromatography with silica gel.…”

“…(14). Each solution of 15 and X (1.95 g), 16 and Y (2.56 g), or 17 and Z (1.91 g) and 10% Pd-C/H 2 (6.2-7.1 g) in methanol containing 10% formic acid (170-215 ml) was individually stirred under nitrogen for 2 h at room temperature, filtered through Celite, and then concentrated to respectively give debenzylated Solubility of -L-fucopyranosyl-CDs 11-14. Water was carefully added in 10-100-ml portions to a glass vessel containing 100 mg of a dried sample of either -L-Fuc-CDs 11, 12, 13 or 14, and the volumes of solvent required for complete dissolution of the -L-Fuc-CDs within 30 min at 25 C and 50 C were measured, with vigorous shaking for 30-s periods at 5-min intervals.…”

“…[11][12][13][14][15] The water solubility of branched cyclomaltoheptaoses (CDs) linked with mono-or oligosaccharides containing glucose, galactose, mannose and maltose is approximately 50-100 times greater than that of CD. 16) Therefore, the use of branched CD inclusion complexes is expected to result in the increased bioavailability of insoluble and unstable drugs. 2,3) L-Fucose (L-Fuc), a deoxyhexose, is a biologically relevant monosaccharide that is widely distributed in the sugar chains of glycoproteins and glycolipids, especially -L-fucopyranosyl residues.…”

Enzymatic synthesis of a 2-O-α-d-glucopyranosyl cyclic tetrasaccharide by kojibiose phosphorylase

“…NMR spectral data were recorded for 1-5% solutions in D 2 O at 27°C with a JNM-AL300 spectrometer ( 1 H 300.4 MHz, 13 C 75.45 MHz: JEOL, Tokyo, Japan). The chemical shifts were expressed in ppm downfield from the signal of 3-(trimethylsilyl)-1-propane-sulfonic acid sodium salt (TPS) used as an internal standard.…”

Determination of Branched β-Cyclodextrin–Prostaglandin Complexes Using Electrospray Ionization Mass Spectrometry

“…The hemolytic activities of branched CDs linked with saccharides toward human erythrocytes in an isotonic solution were lower than those of non-branched CDs. 4) Branched CDs linked with saccharides are outstanding in their water-solubility for otherwise insoluble compounds. Therefore, inclusion complexes with branched CDs can be expected to increase the bioavailability of insoluble drugs in which non-branched CD is replaced by branched CDs.…”