Picolinyl group as an efficient alcohol protecting group: cleavage with Zn(OAc)2·2H2O under a neutral condition

As an efficient alcohol protecting group, picolinates (Pic), prepared from the corresponding alcohols using commercial picolinoyl chloride, are readily cleaved by Zn(OAc)₂ or Cu(OAc)₂, even in the presence of other common alcohol protecting groups. Moreover, the picolinyl group at C-2 position in carbohydrates can be selectively cleaved to give methyl 4,6-O-benzylidene-3-O-picolinyl-α-d-glucopyranoside and 3-O-picolinyl methyl-4,6-O-benzylidene-α-d-galactopyranoside in good yields.     

Synthesis of novel chiral phosphines from α,α-trehalose

New disaccharide chiral phosphines, such as 4,6-O-benzylidene-2-(diphenylphosphino)-2-deoxy-α-d-altropyranosyl-(1,1)-4,6-O-benzylidene-2-(diphenylphosphino)-2-deoxy-α-d-altropyranoside 1 and 2-(diphenylphosphino)-2-deoxy-4,6-O-isopropylidene-α-d-altropyranosyl-(1,1)-2-(diphenylphosphino)-2-deoxy-4,6-O-isopropylidene-α-d-altropyranoside 9, were prepared from α,α-trehalose. We also succeeded in the synthesis of polyhydroxy chiral diphosphine 2-(diphenylphosphino)-2-deoxy-α-d-altropyranosyl-(1,1)-2-(diphenylphosphino)-2-deoxy-α-d-altropyranoside 5 by deprotection of isopropylidene groups.     

Design and synthesis of new carbohydrate-lithocholic acid conjugates linked via 1,2,3-triazole rings

In this work, we report the synthesis of a novel carbohydrate-lithocholic acid conjugate linked through of 1,2,3-triazole rings and its derivatives in good to excellent yields. The conjugate was synthesized via copper-catalyzed azide?alkyne cycloaddition (CuAAC) from methyl 4,6-O-benzylidene-2,3-di-O-propargyl-α-d-glucopyranoside and methyl 3-azidolithocholate. The structures of all new compounds were properly characterized by infrared (IR), high-resolution mass spectroscopy (HRMS) and one- and two-dimensional nuclear magnetic resonance (NMR).     

Syntheses of a new type of chiral phosphines from glucose

Methyl 3-deoxy-3-(diphenylphosphino)-4,6-O-benzylidene-α-D-altropyranoside (1) and methyl 2-deoxy-2-(diphenylphosphino)-4,6-O-benzylidene-α-D-altropyranoside (2) were prepared from methyl 2,3-anhydro-4,6-O-benzylidene-O-D-mannopyranoside and methyl 2,3-anhydro-4,6-O-benzyl-idene-α-D-allopyranoside,respectively,via regioselective and stcreospecific ring-opening reactions in high yields.Compounds 1 and 2 were oxidized to give the corresponding phosphine oxides (3 and 4).     

Towards cyclic,conformationally constrained,fluorine-containing β-amino acid derivatives from d-glucose

Novel, potentially bioactive, fluorinated branched-chain monosaccharides were obtained by reaction of diethylaminosulphur trifluoride (DAST) with a series of methyl 3-C-cyano-3-ethoxycarbonyl-β-d-glucopyranoside derivatives, including the 4,6-O-benzylidene derivative and their 3-C-(N-protected aminomethyl) reduction products, as well as the phenyl 3-C-cyano-3-ethoxycarbonyl-1-thio-α-d-(and β-d-)glucopyranosides. The absolute configuration at C(3) was unambiguously assigned for all compounds on the basis of X-ray crystallographic analysis of methyl 4,6-O-benzylidene-3-C-cyano-3-deoxy-3-ethoxycarbonyl-β-d-glucopyranoside, corroborating the previous tentative assignment by other authors for the 4,6-unprotected compound. The course of the fluorination depended on the reaction temperature and the substitution pattern of the substrate. Thus, for methyl 3-C-cyano-3-ethoxycarbonyl-β-d-glucopyranoside, fluorination occurred exclusively at C(6), but for the phenylthio analogue, a 2-deoxy-2-phenylthio-α-d-manno-configured glycosyl fluoride and its 6-fluoro derivative were obtained, resulting from the expected rearrangement reaction, whilst starting from the phenylthio α anomer, only the unrearranged 6-fluoro compound was formed. Rearrangement was also observed in the fluorination of methyl 4,6-O-benzylidene-3-C-(N-protected aminomethyl)-β-d-glucopyranoside, which led to the 2-O-methyl-α-d-mannopyranosyl fluoride derivative as the sole product. This methodology may constitute a simple route to enantiopure conformationally constrained cyclic fluorinated β-amino acids having the α carbon atom shared with a pyranose ring, although only moderate yields were achieved, particularly in the fluorination step.     

Synthesis of the repeating trisaccharide unit of the cell wall lipopolysaccharide of Escherichia coli type 8

NIS/TfOH mediated glycosidation of methyl 3,4,6-tri-O-benzyl-α-d-mannopyranoside with phenyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α-d-mannopyranoside furnished the corresponding disaccharide derivative in excellent yield and α-selectivity. Zémplen deacetylation of the same followed by reaction with BSP/Tf₂O-preactivated phenyl 4,6-O-benzylidene-2,3-di-O-benzyl-1-thio-α-d-mannopyranoside generated methyl 4,6-O-benzylidene-2,3-di-O-benzyl-β-d-mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α-d-mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α-d-mannopyranoside in very good yield and excellent β-selectivity. Pd/C catalyzed hydrogenation of the latter finally afforded the repeating trisaccharide of Escherichia coli 8 O-antigen as its methyl glycoside.     

Synthese des substances de groupe sanguin—IX: Une synthese du 2-o-(α-l-fucopyranosyl)-3-o-(α-d-galactopyranosyl)-d-galactose,le determinant antigenique du groupe sanguin b

The trisaccharide 2-O-(α-L-fucopyranosyl)-3-O-(α-D-galactopyranosyl)-D-galactose has been synthesised stereospecifically using the imidate procedure. Allyl 3-O-benzoyl-4,6-O-benzylidene-β-D-galactopyranoside was first α-L-fucosylated by 1-O-(N-methyl)-acetimidyl-2,3,4-tri-O-benzyl-β-L-fucopyranose then, after O-debenzoylation, α-D-galactosylated by 1-O-(N-methyl)-acetimidyl 2,3,4,6-tetra-O-benzyl-β-D-galactopyranose. The resulting tri-saccharide has also been obtained from allyl 2-O-benzoyl-4,6-O-benzylidene-β-D-galactopyranoside after α-D-galactosylation, O-debenzoylation and α-L-fucosylation. The glycosylations were performed at room temperature in nitromethane in the presence of p-toluenesulfonic acid. Deallylation followed by catalytic hydrogenolysis gave the B blood-group antigenic determinant. The allyl group was also selectively transformed into hydroxyethyl group.     

A novel seven-membered carbohydrate phostone

Treatment of methyl 2,3-di-O-benzyl-4,6-O-benzylidene-α(β)-d-glucopyranoside with triethyl phosphite and trimethylsilyl trifluoromethanesulfonate affords the seven-membered phostone arising from the attack of reagents on the acetal protecting group.     

Cyanosugars III : The reaction of trimethylsilyl cyanide with keto,epoxy and acetal derivatives of carbohydrates

Reaction of methyl 2-acetamido-4,6-$\text{O}$-benzylidene-2-deoxy-α-$\text{D}$-$\text{ribo}$-hexopyranosid-3-ulose with Me₃SiCN afforded methyl 2-acetamido-4,6-$\text{O}$-benzylidene-3-$\text{C}$-cyano-2-deoxy-3-$\text{O}$-trimethylsilyl-α-$\text{D}$-$\text{allo}$- Reaction of ethyl 4,6-di-$\text{O}$-acetyl-2,3-anhydro-α-$\text{D}$-mannopyranoside with Me₃SiCN gave the corresponding ethyl 4,6-di-$\text{O}$-acetyl-2-$\text{C}$-cyano-2-deoxy-α-$\text{D}$-glucopyranoside. Reaction of methyl 4,6-$\text{O}$-benzylidene-2,3-anhydro-α-$\text{D}$-allopyranoside or methyl 4,6-$\text{O}$-benzylidene-2,3-di-$\text{O}$-tosyl-α-$\text{D}$-glucopyranoside with Me₃SiCN at - 75° or - 50° gave the corresponding methyl 6-$\text{O}$-[(R)-cyano phenyl methyl]-α-$\text{D}$-glyco-pyranosides with high or total regio and stereoselectivity.     

On the relation between the solvent parameters and the physical properties of methyl-4,6-O-benzylidene-α-d-glucopyranoside organogels

This paper reports the mechanisms of gel formation, the thermal properties and the microstructures of the networks of the gels composed of methyl-4,6-O-benzylidene-α-d-glucopyranoside and selected organic solvents: p-xylene, benzene, toluene, diphenyl ether and tetraethoxysilane. The Fourier transform infrared measurements together with simulation spectra, the air bath method and Polarized Optical Microscopy were employed in our studies. The experimental data show that the solvent has an influence on the microstructure of the gel network but there is no predictable influence of the solvent polarity on the shape of the formed gelator aggregates and correspondingly on the fibrous assemblies as revealed by the different microstructure of the gel network. Independently of the solvent polarity, the studied gelator, like other methyl-4,6-O-benzylidene derivatives of monosaccharides, formed gels through the formation of a hydrogen-bond network. The solvent parameters, such as the dielectric constant, Hildebrand solubility parameter, the polarity scale E_T and the Kamlet–Taft parameters were considered to quantify solvent effects on the gelation. The conclusions about the correlations are of interest but only to this particular sugar based gels.     

Direct vinylation of glucose derivatives with acetylene

Vinyl ethers, promising chiral carbohydrate synthons, have been synthesized by the addition of glucose acetals (1,2:5,6-di-O-isopropylidene-α-d-glucofuranose, methyl 4,6-O-benzylidene-α-d-glucopyranoside, 1,2-O-cyclohexylidene-α-d-glucofuranose, methyl α-d-glucopyranoside) to acetylene under atmospheric and elevated pressures in an autoclave in the presence of superbase catalytic systems (KOH-DMSO, t-BuOK-DMSO). The complete vinylation of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose and methyl α-d-glucopyranoside has been realized under elevated pressure of acetylene in the system KOH-THF as well.     

A stereocontrolled construction of 2-azido-2-deoxy-1,2-cis-α-galactosidic linkages utilizing 2-azido-4,6-O-benzylidene-2-deoxygalactopyranosyl diphenyl phosphates: stereoselective synthesis of mucin core 5 and core 7 structures

TMSOTf-promoted glycosidation of 2-azido-4,6-O-benzylidene-2-deoxygalactosyl diphenyl phosphates with fluorenylmethoxycarbonyl (Fmoc)-protected serine and threonine derivatives in THF/Et₂O (1:1) gave glycosyl amino acids in high yields and with excellent levels of α-selectivity (α/β=94:6–95:5). The synthetic utility of the present glycosidation method was demonstrated by a stereoselective synthesis of mucin-type glycopeptide core 5 and core 7 building blocks, which are suitable for Fmoc-based solid-phase synthesis of O-glycopeptides.     

Asymmetric C–C bond forming reactions with chiral crown catalysts derived from d-glucose and d-galactose

New chiral monoaza-15-crown-5 derivatives anellated to methyl-4,6-O-benzylidene-α-d-glucopyranoside 2a, 2e, 2g–i and to methyl-4,6-O-benzylidene-α-d-galactopyranoside 3a, 3e, 3i have been synthesized. These crown ethers showed significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (87% ee), in the Darzens condensation of phenacyl chloride with benzaldehyde (71% ee) and in the self-condensation of phenacyl chloride (64% ee) to give 14. The absolute configurations of (−)-(2R,3S)-epoxy-3-(4-chlorophenyl)-1-phenyl-1-propanone 12 and (−)-4-chloro-(2R,3S)-epoxy-1,3-diphenyl-1-butanone 14 have also been determined by X-ray diffraction.     

Observations on the electron impact induced fragmentation of methyl and phenyl 4,6-O-Benzylideneglucopyranosides

The structure of some rearrangement ions in the electron impact induced fragmentation of methyl 4,6-O-benzylidene-2,3-di-O-methyl-α-D -glucopyranoside and phenyl 4,6-O-benzylidene-2,3-di-O-methyl-β-D -glucopyranoside have been investigated using high resolution, deuterium labelling and linked scan (B,E) techniques. Shifts of methoxyl groups from C-2 and C-3 to C-1 have been confirmed.     

Preparation and structural determination of methyl 3-C-p-tolylsulfonyl-2-C-p-tolylthio-β-d-glucopyanoside derivatives and their 5a-carba-dl-analogs having non-chair conformation in solutions

Methyl 4,6-O-benzylidene-2,3-dideoxy-3-C-p-tolylsulfonyl-2-C-p-tolylthio-β-d-glucopyranoside and its 5a-carba-dl-analog exit mainly in a non-chair conformation in solutions, but the latter occupies a chair conformation in a solid state.     

Synthesis of Methyl 2-Acetamido-4,6-di-O-acetyl-3-S-acetyl-2-deoxy-3-thio-α-D-mannopyranoside

Methyl-2-acetamido-4,6-di-O-acetyl-3-S-acetyl-2-deoxy-3-thio-α-D-mannopy-ranoside has been synthesized by conversion of methyl 2-amino-2-deoxy-4,6-O-benzylidene-α-D-altropyranoside into the corresponding 3-O-methanesulfony1-2-N-[(methylthio)thiocarbonyl]derivative followed by intramolecular displacement of the 3-O-methanesulfonyloxy group with the (methylthio)thiocarbamoyl group.     

Syntheses of Model Oligosaccharides of Biological Significance. VI. Glycosylation at C-3 of Galactose: A Synthesis of Trideuterio-Methyl 3-O-(-Acetamido-2-Deoxy-β-D-Glucopyranosyl)-β-D-Galactopyranoside

The title disaccharide was prepared by glycosylation of either methyl trideuteriomethyl 2-O-benzoyl-4,6-benzylidene-β-D-galactopyranoside or trideuteriomethyl-4,6-O-benzylidene-β-D-galactopyranoside with 3,4,6-tri-Oi-acetyl 2-deoxy-2-phthalimido-β-D-glucopyranosyl bromide using silver zeolite 13X or silver triflate as promoters.     

Synthesis of d-rubranitrose by using a novel method for constructing functionalized branched-chain structures

Convenient synthesis of d-rubranitrose from d-glucose was achieved by using simple and novel methods for deoxygenation and construction of functionalized branched-chain structures. The total yield of d-rubranitrose from methyl 4,6-O-benzylidene-α-d-glucopyranoside (1) was 4.9%.     

The Synthesis of Four Dideoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract

Four derivatives of β-maltosyl-(1→4)-trehalose were prepared, each with two deoxy functions in one of the constitutive disaccharide building blocks. 2,3-Di-O-acetyl-4,6-dideoxy-4,6-diiodo-α-D-galactopyranosyl- (1→4) ?1,2,3,6-tetra-O-acetyl-D-glucopyranose (3) was employed as a precursor for the 4?,6?-dideoxygenated tetrasaccharide 9: coupling of 3 with 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzylidene-α-D-glucopyranoside (4) furnished the tetrasaccharide 5 which was deiodinated and deprotected to yield the target tetrasaccharide 9. Secondly, the dideoxygenated maltose derivative 3-deoxy-4,6-O-isopropylidene-2-O-pivaloyl-β-D-glucopyranosyl- (1→4) ?1,6-anhydro-3-deoxy-2-O-pivaloyl-β-D-glucopyranose (10) was ring-opened to the anomeric acetate 11. A [2+2] block synthesis with 4 in TMS triflate mediated glycosylation gave a tetrasaccharide which was deprotected to the 3″,3?-dideoxygenated analogue of β-maltosyl-(1→4)-trehalose. For the third tetrasaccharide, 2,3,2″,3′-tetra-O-benzyl-α,α-trehalose was iodinated at the primary positions and deiodinated in the presence of palladium-on-carbon, then this acceptor was selectively glycosylated with hepta-O-acetyl-maltosyl bromide (20). Removal of protective groups furnished the maltosyl trehalose tetrasaccharide deoxygenated at positions C-6 and C-6′. to prepare a 3,3′-dideoxygenated trehalose, the free hydroxyl groups of 2-O-benzyl-4,6-O-(R)-benzylidene-α-D-glucopyranosyl 2-O-benzyl-4,6-O-(R)-benzylidene-α-D-glucopyranoside (25) were reduced by Barton-McCombie deoxygenation. One of the benzylidene groups was opened reductively with sodium cyanoborohydride. The resulting free hydroxyl group at the 4′-position was glycosylated in a Koenigs-Knorr reaction with 20 to yield the 3,3′-dideoxygenated tetrasaccharide 32, the fourth target oligosaccharide, after deprotection.     

The Effect of the Side Chain on Gelation Properties of Bile Acid Alkyl Amides

Six bile acid alkyl amide derivatives were studied with respect to their gelation properties. The derivatives were composed of three different bile acids with hexyl or cyclohexyl side chains. The gelation behaviour of all six compounds were studied for 36 solvents with varying polarities. Gelation was observed mainly in aromatic solvents, which is characteristic for bile-acid-based low molecular weight gelators. Out of 108 bile acid-solvent combinations, a total of 44 gel systems were formed, 28 of which from lithocholic acid derivatives, only two from deoxycholic acid derivatives, and 14 from cholic acid derivatives. The majority of the gel systems were formed from bile acids with hexyl side chains, contrary to the cyclohexyl group, which seems to be a poor gelation moiety. These results indicate that the spatial demand of the side chain is the key feature for the gelation properties of the bile acid amides.