A highly efficient and convergent synthesis of a hexasaccharide, a dimer of the repeating unit of the antigen O2 polysaccharide of Stenotrophomonas maltophilia.

A highly efficient and convergent synthesis of a hexasaccharide, which is a dimer of the repeating unit of the antigen O2 polysaccharide of Stenotrophomonas maltophilia, was achieved via coupling of 2,3,4-tri-O-acetyl-alpha-L-xylopyranosyl bromide with the tetrasaccharide, allyl 4-O-{3-O-[4-O-(3,4-di-O-benzoyl-alpha-L-rhamnopyranosyl)-2,3,6-tri-O-ben zoyl -alpha-D-mannopyranosyl]-4-benzoyl-alpha-L-rhamnopyranosyl}-2,3,6-tri-O- benzoyl-alpha-D-mannopyranoside (18) by the Koenigs-Knorr method followed by deacylation. Compound 18 was readily prepared from the coupling of the disaccharide trichloroacetimidate, 4-O-(2-O-acetyl-3,4-di-O-benzoyl-alpha-L-rhamnopyranosyl)-2,3,6-tri-O- benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (8) with the disaccharide acceptor, allyl 4-O-(2-O-acetyl-4-O-benzoyl-alpha-L-rhamnopyranosyl)-2,3,6-tri-O-benzoyl - alpha-D-mannopyranoside (16), and both 8 and 16 were prepared via the trichloroacetimidate method from simple starting materials. The sole use of acyl protecting groups substantially simplified protection and deprotection, and the allyl group at the reducing end of allyl 4-O-{2-O-[2,3,4-tri-O-acetyl-beta-L-xylopyranosyl]-3-O-[4-O-(2-O-(2,3,4- tri-O-acetyl-beta-L-xylopyranosyl)-3,4-di-O-benzoyl-alpha-L-rhamnopyrano syl) -2,3,6-tri-O-benzoyl-alpha-D-mannopyranosyl]-4-O-benzoyl-alpha- L-rhamnopyranosyl}-2,3,6-tri-O-benzoyl-alpha-D-mannopyranoside 19 allowed further chemical transformation.     

Synthesis of trisaccharide methyl glycosides related to fragments of the capsular polysaccharide of Streptococcus pneumoniae type 18C.

The synthesis is reported of methyl 3-O-(4-O-beta-D-galactopyranosyl-alpha-D- glucopyranosyl)-alpha-L-rhamnopyranoside (1), methyl 2-O-alpha-D-glucopyranosyl-4-O-beta-D-glucopyranosyl-beta-D- galactopyranoside (3), methyl 3-O-(4-O-beta-D-galactopyranosyl-alpha-D-glucopyranosyl)-alpha-L- rhamnopyranoside 3"-(sn-glycer-3-yl sodium phosphate) (2), and methyl 2-O-alpha-D-glucopyranosyl-4-O-beta-D- glucopyranosyl-beta-D-galactopyranoside 3-(sn-glycer-3-yl sodium phosphate) (4), which are trisaccharide methyl glycosides related to fragments of the capsular polysaccharide of Streptococcus pneumoniae type 18C ([----4)-beta-D- Glcp-(1----4)-[alpha-D-Glcp-(1----2)]-[Glycerol-(1-P----3)]-beta-D-Galp - (1----4)-alpha-D-Glcp-(1----3)-alpha-L-Rhap-(1----]n). Ethyl 4-O-acetyl-2,3,6-tri-O-benzyl-1-thio-beta-D-glucopyranoside (10) was coupled with benzyl 2,4-di-O-benzyl-alpha-L-rhamnopyranoside (6). Deacetylation of the product, followed by condensation with 2,4,6-tri-O-acetyl-3-O-allyl-alpha-D-galactopyranosyl trichloroacetimidate (18), gave benzyl 2,4-di-O-benzyl-3-O-[2,3,6-tri-O- benzyl-4-O-(2,4,6-tri-O-acetyl-3-O-allyl-beta-D-galactopyranosyl)-alpha- D- glucopyranosyl]-alpha-L-rhamnopyranoside (19). Acetolysis of 19, followed by methylation, deallylation (----22), and further deprotection afforded 1. Condensation of methyl 2,4-di-O-benzyl-3-O-[2,3,6-tri-O-benzyl-4-O-(2,4,6-tri- O-acetyl-beta-D-galactopyranosyl)-alpha-D-glucopyranosyl]-alpha-L- rhamnopyranoside (22) with 1,2-di-O-benzyl-sn-glycerol 3-(triethyl-ammonium phosphonate) (24), followed by oxidation and deprotection, yielded 2. Condensation of ethyl 2,3,4,6-tetra-O-benzyl-1-thio-beta-D-glucopyranoside (27) with methyl 3-O-allyl-4,6-O-benzylidene-beta-D-galactopyranoside (28), selective benzylidene ring-opening of the product, coupling with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (31), and deallylation afforded methyl 6-O-benzyl-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-2-O- (2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl)-beta-D-galactopyranoside (33). Deprotection of 33 gave 3, and condensation of 33 with 24, followed by oxidation and deprotection, gave 4.     

Nonaqueous synthesis of a selectively modified, highly anionic sulfopropyl ether derivative of cyclomaltoheptaose (beta-cyclodextrin) in the presence of 18-crown-6

A highly anionic cyclomaltooligosaccharide (cyclodextrin, CD) derivative containing sulfopropyl functional groups on the primary face of the CD was synthesized. Heptakis(2,3-di-O-methyl)cyclomaltoheptaose [heptakis(2,3-di-O-methyl)-beta-cyclodextrin] was reacted with 1,3-propane sultone and potassium hydride (KH) in anhydrous tetrahydrofuran in the presence of 18-crown-6 to yield highly substituted potassium heptakis(2,3-di-O-methyl-6-O-sulfopropyl)cyclomaltoheptaose [heptakis(KSPDM)-beta-CD] with an average degree of substitution (DSCE) of 6.9 as determined by inverse detection capillary electrophoresis (CE). The principal species in the product is the fully substituted heptakis(KSPDM)-beta-CD. Complete NMR assignments of the hydrogen and carbon atoms are made using a combination of gCOSY and gHSQC. In the absence of 18-crown-6, the reaction generates a mixture of multiply charged derivatives with average DSCE of 4.1. The possible roles of the crown ether in the reaction are discussed. The ROESY NMR spectrum of the inclusion complex that forms between heptakis(KSPDM)-beta-CD and 2-naphthoic acid in D2O reveals that 2-naphthoic acid inserts with the carboxyl group toward the derivatized primary rim of the cyclodextrin.     

Structure of the inclusion complexes of heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin with indole-3-butyric acid and 2,4-dichlorophenoxyacetic acid

The crystal structures of the complexes of heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin with indole-3-butyric acid and with 2,4-dichlorophenoxyacetic acid were studied by X-ray diffraction. The complexes crystallize in the monoclinic P2(1) space group. The host molecules are elliptically puckered and stacked along the a crystal axis, in a head-to-tail fashion, forming columns. One primary methoxy group of the host molecule of the complex with indole-3-butyric acid has the unusual trans-gauche conformation for permethylated CDs. All the secondary O-3-CH(3) methoxy groups, some secondary O-2-CH(3) and some primary methoxy groups pointing inwards the cavity enclose the indole or the 2,4-dichlorophenoxy moieties of the guest molecules inside the cavity, while the chains of the guests protrude between two adjacent host molecules of the columns. The mean planes of the indole and 2,4-dichlorophenoxy moieties of the guests are nearly perpendicular to the mean planes of the elliptical heptagons defined by the O-4n atoms of the hosts. The carboxyl group of the guests form hydrogen bonds with oxygen atoms of the host molecules or with the water molecules found in the space between the complexes of the same column.     

Synthesis of aminoethylglycosides with oligosaccharide GM1 and asialo-GM1 ganglioside chains

4'-O-Glycosylation of 2-azidoethyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O- benzyl-6-O-benzoyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside with a disaccharide donor, 4-trichloroacetamidophenyl 4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-beta-D- galactopyranosyl)-1-thio-2-trichloroacetamido-beta-D-galactopyranoside, in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid resulted in a tetrasaccharide, 2-azidoethyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->3)- (4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-beta-D-galactopyranosyl)- (1-->4)-(2,3-di-O-benzyl-6-O-benzoyl-beta-D-galactopyranosyl)- (1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside, in 69% yield. The complete removal of O-protecting groups in the tetrasaccharide, the replacement of N-trichloroacetyl by N-acetyl group, and the reduction of the aglycone azide group to amine led to the target aminoethyl glycoside of beta-D-Gal- (1-->3)-beta-D-GalNAc-(1-->4)-beta-D-Gal-(1-->4)-beta-D-Glc-OCH2CH2NH2 containing the oligosaccharide chain of asialo-GM1 ganglioside in 72% overall yield. Selective 3'-O-glycosylation of 2-azidoethyl 2,3,6-tri-O- benzyl-4-O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside with thioglycoside methyl (ethyl 5-acetamido-4,7,8,9-tetra-O- acetyl-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and trifluoroacetic acid afforded 2-azidoethyl [methyl (5-acetamido-4,7,8,9-tetra-O-acetyl- 3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and tri-fluoracetic acid afforded 2-azidoethyl[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl- 3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl) (2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D- glucopyranoside, the selectively protected derivative of the oligosaccharide chain of GM3 ganglioside, in 79% yield. Its 4'-O-glycosylation with a disaccharide glycosyl donor, (4-trichloroacetophenyl-4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O- acetyl-beta-D-galactopyranosyl) 1-thio-2-trichloroacetamido-beta-D-galactopyranoside in dichloromethane in the presence of N-iodosuccinimide and trifluoroacetic acid gave 2-azidoethyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)- (1-->3)-(4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-beta-D- galactopyranosyl)-(1-->4)-[[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D- galacto-2-nonulopyranosyl)onate]-(2-->3)]-(2,6-di-O-benzyl-beta-D- galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside in 85% yield. The resulting pentasaccharide was O-deprotected, its N-trichloroacetyl group was replaced by N-acetyl group, and the aglycone azide group was reduced to afford in 85% overall yield aminoethyl glycoside of beta-D-Gal-(1-->3)-beta-D-GalNAc-(1-->4)-[alpha-D-Neu5Ac-(2-->3)]- beta-D-Gal-(1-->4)-beta-D-Glc-OCH2CH2NH2 containing the oligosaccharide chain of GM1 ganglioside. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.     

Separation and absolute configuration of the enantiomers of a degradation product of the new inhalation anesthetic sevoflurane

In a rebreathing anesthesia circuit, the inhaled anesthetic sevoflurane degrades into at least two products, termed "compound A" and "compound B." The enantiomer separation of the chiral compound B (1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane ) by capillary gas chromatography (cGC) using heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin as chiral selector was studied. With this cyclodextrin derivative diluted in the polysiloxane PS 86, an unprecedented high separation factor alpha of 4.1 (at 30 degrees C) was found. Consequently, the enantiomers of compound B were isolated by preparative GC and their specific rotations were measured. In addition, their absolute configurations were determined by X-ray crystallography. To collect the X-ray data, single crystals of both enantiomers were grown in situ on the diffractometer. The levorotatory enantiomer B(-) has the R-configuration while the dextrorotatory enantiomer B(+) has the S-configuration. The elution order of the compound B enantiomers on heptakis (2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-beta-cyclodextrin is R before S.     

Chemical synthesis of 6"'-alpha-maltotriosyl-maltohexaose as substrate for enzymes in starch biosynthesis and degradation.

A branched nonasaccharide 6"'-alpha-maltotriosyl-maltohexaose was synthesised in 40 steps from D-glucose and maltose. Phenyl O-(2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl)-(1-->4)-O- (2,3,6-tri-O-benzyl-alpha-D-glucopyranosyl)-(1-->4)-2,3-di-O-benzyl-1-th io- beta-D-glucopyranoside and O-(2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl)-(1-->4)-O-(2,3,6-tri- O-benzyl-alpha-D-glucopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-alpha, beta-D-glucopyranosyl trichloroacetimidate were coupled by a general condensation reaction to form the per-O-benzylated branched hexasaccharide phenyl thioglycoside. The phenylthio group of this compound was converted into a trichloroacetimidate, which was coupled with phenyl O-(2,3,6-tri-O-benzyl-alpha-D-glucopyranosyl)-(1-->4)-O-(2,3,6-tri-O- benzyl-alpha-D-glucopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-1-thio-beta-D- glucopyranoside to afford the per-O-benzylated branched nonasaccharide phenyl thioglycoside. Replacement of the phenylthio group with a free OH-group followed by hydrogenolysis gave the desired product. The synthons reported for this synthesis constitute a versatile tool for the chemical synthesis of other complex carbohydrates.     

Structure of the complex of heptakis(2,6-di-O-methyl)-beta-cyclodextrin with (2,4-dichlorophenoxy)acetic acid

The structure of the complex formed by heptakis(2,6-di-O-methyl)-beta-cyclodextrin and (2,4-dichlorophenoxy)acetic acid was studied by X-ray diffraction. The dichlorophenyl moiety of the guest molecule was found outside the host hydrophobic cavity in the primary methoxy groups region whereas the oxyacetic acid chain penetrates the cavity from the primary face. The host molecules stacks along the a crystal axis forming a column. In the space between three successive hosts of the column, a guest molecule is accommodated.     

Synthesis and mass spectra of 4-O-acetyl-1,5-anhydro-2,3,6-tri-O -(methoxycarbonylmethyl)-D-glucitol and the positional isomers of 4- O-acetyl-1,5-anhydro-di-O-(methoxycarbonylmethyl)-O-methyl-D-glucitol and 4-O-acetyl-1,5-anhydro-O-(methoxycarbonylmethyl)-di-O-methyl-D-glucitol .

Reductive cleavage of fully methylated, partially O-carboxymethylated cellulose had previously been shown to produce 4-O-acetyl-1,5-anhydro-2,3,6-tri-O-methyl-, -2-O-(methoxycarbonylmethyl)-3,6-di-O-methyl-, -3-O-(methoxycarbonylmethyl)-2,6-di-O-methyl-, -6-O-(methoxycarbonylmethyl)-2,3-di-O-methyl-, -2,3-di-O-(methoxycarbonylmethyl)-6-O-methyl-, -2,6-di-O-(methoxycarbonylmethyl)-3-O-methyl-, -3,6-di-O-(methoxycarbonylmethyl)-2-O-methyl-, and -2,3,6-tri-O-(methoxycarbonylmethyl)-D-glucitol. Described herein is the independent synthesis of these derivatives, except for the first, which had been reported. In addition, their 1H-n.m.r. spectra, chemical-ionization (NH3) mass spectra, and electronionization mass spectra are tabulated.     

Synthesis of aminoethyl glycosides of the carbohydrate chains of glycolipids Gb3, Gb4 i Gb5

4-O-Glycosylation of 2-azidoethyl 2,3,6-tri-O-benzoyl-4-O-(2,3,6-tri-O-benzoyl-beta-D-galactopyranosyl)-beta- D-glucopyranoside with ethyl 2,3,4,6-tetra-O-benzyl- and ethyl 3-O-acetyl-2,4,6-tri-O-benzyl-1-thio-alpha-D-galactopyranoside in the presence of methyl trifluoromethanesulfonate led to trisaccharide 2-azidoethyl (2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl)-(1-->4)- (2,3,6-tri-O-benzoyl-beta-D-galactopyranosyl)-(1-->4)2,3,6-tri-O- benzoyl-beta-D-glucopyranoside and its 3"-O-acetylated analogue, 2-azidoethyl (3-O-acetyl-2,4,6-tri-O-benzyl- alpha-D-galactopyranosyl)-(1-->4)-(2,3,6-tri-O-benzoyl-beta-D- galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranoside, in yields of 85 and 83%, respectively. Deacetylation of the latter compound and subsequent glycosylation with 4-trichloroacetamidophenyl 3,4,6-tri-O-acetyl-2-deoxy-1-thio-2-trichloroacetamido-beta-D- galactopyranoside and 4-trichloroacetamidophenyl 4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O- acetyl-beta-D-galactopyranosyl)-1-thio-2-trichloroacetamido-beta-D- galactopyranoside in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid resulted in the corresponding selectively protected derivatives of tetrasaccharide GalNAc(beta 1-->3)Gal(alpha 1-->4)Gal(beta 1-->4)Glc beta-OCH2CH2N3 and pentasaccharide Gal(beta 1-->3)GalNAc(beta 1-->3)Gal(alpha 1-->4)Gal(beta 1-->4)Glc beta-OCH2CH2N3 in 88 and 73% yields, respectively. Removal of O-protecting groups, substitution of acetyl group for N-trichloroacetyl group, and reduction of the aglycone azide group resulted in the target 2-aminoethyl globo-tri-, -tetra-, and -pentasaccharide, respectively.     

An efficient synthesis of ganglioside GM3: highly stereocontrolled glycosylations by use of auxiliaries

An efficiently stereocontrolled total synthesis of GM3 alpha-D-Neup5Ac-(2----3)-beta-D-Galp-(1----4)-beta-D-Glcp-(1----1) -Cer was achieved by employing both methyl 5-acetamido-4,7,8,9-tetra-O-benzyl-2-bromo-2,3,5-trideoxy-3- phenylthio-D-erythro-beta-L-gluco-2-nonulopyranosonate for the key sialylation step, and O-[methyl(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha -D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-(2,4,6-tri-O- acetyl-beta-D-galactopyranosyl-(1----4)-3,6-di-O-acetyl-2-O-pivaloyl- alpha-D-glucopyranosyl trichloroacetimidate and fluoride for the key coupling step with a ceramide derivative. These two steps were significantly altered and improved in comparison with our previous synthesis that had been executed without use of stereocontrolling auxiliaries. GM3 was obtained in 4.5% overall yield in 19 steps starting from allyl O-(2,6-di-O-acetyl-3,4-O-isopropylidene-beta-D-galactopyranosyl)-(1----4 )-2,3,6-tri-O-acetyl-beta-D-glucopyranoside.     

Synthesis of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->3)]-beta-D-GlcpOLauryl, an oligosaccharide with anti-tumor activity

A concise and effective synthesis of lauryl heptasaccharide 17 was achieved from the key intermediates lauryl 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2,4-di-O-benzoyl-beta-D-glucopyranoside (10) and isopropyl 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-1-thio-beta-D-glucopyranoside (15). The key trisaccharide glycosyl acceptor 10 was constructed by coupling 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (3) with lauryl 6-O-acetyl-2,4-di-O-benzoyl-beta-D-glucopyranoside (9), followed by deacetylation. The thioglycoside donor 15 was obtained by condensation of 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11) with isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (12), followed by debenzylidenation and acetylation. A bioassay of the inhibition of S180 noumenal tumors showed that lauryl heptasaccharide 17 could be employed as a potential agent for cancer treatment.     

Total synthesis of globotriaosyl-E and Z-ceramides and isoglobotriaosyl-E-ceramide

Stereoselective, total synthesis of O-alpha-D-galactopyranosyl-(1----4) -O-beta-D-galactopyranosyl-(1----4)-O-beta-D-glucopyranosyl-(1----1)-N -tetracosanoyl-[2S,3R,4E (and 4Z)]-sphingenine and O-alpha-D -galactopyranosyl-(1----3)-O-beta-D-galactopyranosyl-(1----4)-O-beta-D -glucopyranosyl-(1----1)-N-tetracosanoyl-(2S,3R,4E)-sphin gen ine was achieved by using O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl) -(1----4)-O-(2,3,6-tri-O-acetyl-beta-D-galactopyranosyl)-(1----4)-2,3,6- tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate, O-(2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl) -(1----4)-O-(2,3,6-tri-O-acetyl-beta-D-galactopyranosyl)-(1----4)-2,3,6- tri-O-acetyl-alpha (and beta)-D-glucopyranosyl fluoride, and O-(2,3,4,6-tetra-O-acetyl-alpha-D -galactopyranosyl)-(1----3)-O-(2,3,6-tri-O-acetyl-beta-D-galactopyran osyl)-(1----4)-2,3,6-tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate.     

Group-Recognition Ability of Derivatized β-Cyclodextrin as Studied by the ESR Spin Probing Technique

The effect of modifying the entrance face of β-cyclodextrin on the inclusion of various functional groups in aminoxyl spin probes was determined by the use of heptakis (2,6-O-dimethyl)-β-cyclodextrin and heptakis (2,3,6-O-triacetyl)-β-cyclodextrin. The methylation of six of the secondary hydroxyl groups on the wider end of β-cyclodextrin has a variable effect on the association constant of inclusion depending on the nature of the included group. The role of the methoxy group on the rim is discussed on the basis of the thermodynamic data derived from association constants. Contrary to the unmodified β-cyclodextrin the pH of the solution does not influence the inclusion behaviour.     

Synthesis and biological evaluation of 2-amino-2-deoxy- and 6-amino-6-deoxy-cyclomaltoheptaose polysulfates as synergists for angiogenesis inhibition

2-Amino-2-deoxy-cyclomaltoheptaose was prepared from β-cyclodextrin perbenzoate [heptakis(2,3,6-tri-O-benzoyl)cyclomaltoheptaose] by a series of reactions including selective de-O-benzoylation at C-2 of one of the perbenzoylated -glucopyranosyl moieties, oxidation to the 2-ulose derivative, oxime formation, and reduction to the 2-amino-2-deoxy- -glucose moiety. This compound and 6-amino-6-deoxycyclomaltoheptaose accessible from β-cyclodextrin through the known procedure were sulfated to give polysulfated aminocyclomaltoheptaose derivatives (3, 5). Employing β-cyclodextrin polysulfate as a reference compound, the synergistic effects of 3 and 5 for cortexolone on angiogenesis inhibitory activity were examined by rabbit-corneal micropocket assay system. In contrast to the significant anti-angiogenesis activity of the β-cyclodextrin polysulfate-cortexolone pair, neither 3 nor 5 showed any cooperative activity with cortexolone in the inhibition of basic FGF-induced angiogenesis.     

The molecular crystal structure and self-assembly behavior of 6(I)-O-(3-nitrophenyl)cyclomaltoheptaose

The mono-modified beta-cyclodextrin derivative, 6(I)-O-(3-nitrophenyl)cyclomaltoheptaose{mono[6-O-(3-nitrophenyl)]-beta-cyclodextrin} was synthesized, and its crystal structure was determined by single-crystal X-ray analysis. The crystal structure suggests that the 3-nitrophenyl substituent group is inserted into the adjacent beta-cyclodextrin cavity from the secondary hydroxyl side, and the molecules are stacked along the twofold screw axis to form an infinite one-dimensional polymeric chain.     

Synthesis of cerebroside, lactosyl ceramide, and ganglioside GM3 analogs containing beta-thioglycosidically linked ceramide

Coupling of the sodium salt of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose, -beta-D-galactopyranose, O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1----4)-2,3,6-tri-O- acetyl- 1-thio-beta-D-glucopyranose, or O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosylonate)-(2----3)-O-(2,3-di-O-acetyl-6-O-bezoyl -beta-D- galactopyranosyl)-(1----4)-3-O-acetyl-2,6-di-O-benzoyl-1-thio-beta-D- glucopyranose, which were prepared from the corresponding 1-S-acetates, 1, 3, 6, and 9, with (2S,3R,4E)-2-azido-3-O-benzoyl-1-O-(p-tolylsulfonyl)-4-oc tadecene-1,3-diol (12) derived by tosylation of 11, gave the corresponding beta-thioglycosides 13, 17, 21, and 25, respectively in good yield. The beta-thioglycosides obtained were converted, via selective reduction of the azide group, condensation with octadecanoic acid, and removal of the protecting groups, into the title compounds.     

Group-Recognition Ability of Derivatized β-Cyclodextrin as Studied by the ESR Spin Probing Technique

The effect of modifying the entrance face of β-cyclodextrin on the inclusion of various functional groups in aminoxyl spin probes was determined by the use of heptakis (2,6-O-dimethyl)-β-cyclodextrin and heptakis (2,3,6-O-triacetyl)-β-cyclodextrin. The methylation of six of the secondary hydroxyl groups on the wider end of β-cyclodextrin has a variable effect on the association constant of inclusion depending on the nature of the included group. The role of the methoxy group on the rim is discussed on the basis of the thermodynamic data derived from association constants. Contrary to the unmodified β-cyclodextrin the pH of the solution does not influence the inclusion behaviour.     

Synthesis of p-nitrophenyl 6(5)-O-benzyl-alpha-maltopentaoside, a substrate for alpha amylases

p-Nitrophenyl alpha-maltopentaoside, having a benzyl group on O-6 of the terminal (nonreducing) D-glucosyl group was prepared by use of a reductive ring-opening reaction. Highly regioselective reduction of p-nitrophenyl O-(2,3-di-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranosyl)-(1----4)- tris[O-(2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl)-(1----4)]-2,3,6-tri- O- benzoyl-alpha-D-glucopyranoside by dimethylamine-borane and p-toluenesulfonic acid, followed by debenzoylation, gave p-nitrophenyl O-(6-O-benzyl-alpha-D-glucopyranosyl)-(1----4)-tris[O-alpha-D-glucopyran osyl- (1----4)]-alpha-D-glucopyranoside. An experiment was done on the mode of action of human pancreatic and salivary alpha amylases on this derivative. The compound is suitable as a substrate for the assay of alpha amylase when used with glucoamylase and alpha-D-glucosidase as coupling enzymes.     

Comparative Enantioseparation of Ketoprofen with Trimethylated α‐, β‐, and γ‐Cyclodextrins in Capillary Electrophoresis and Study of Related Selector–Selectand Interactions Using Nuclear Magnetic Resonance Spectroscopy

The enantiomers of ketoprofen were separated by capillary electrophoresis using the (2,3,6‐tri‐O‐methyl)‐derivatives of α‐, β‐, and γ‐cyclodextrin (CyD) as chiral selectors. The affinity pattern of the ketoprofen enantiomers toward these CyDs changed depending on their cavity size. Thus, with hexakis (2,3,6‐tri‐O‐methyl)‐α‐CyD and heptakis (2,3,6‐tri‐O‐methyl)‐β‐CyD, the R enantiomer of the drug migrated first, whereas the enantiomer migration order was reversed in the presence of octakis(2,3,6‐tri‐O‐methyl)‐γ‐CyD. The change in the migration order was rationalized on the basis of changes in the structure of the complexes between the ketoprofen enantiomers and the chiral selectors as derived from nuclear magnetic resonance spectroscopy experiments. Chirality, 25:79–88, 2013.© 2012 Wiley Periodicals, Inc.