Synthesis of p-trifluoroacetamidophenyl O-α-D-galactopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→4)-α-L-rhamnopyranoside

The role of exposed tyrosine side-chains in enzyme-catalysed reactions has been studied for porcine-pancreatic alpha-amylase, sweet-potato beta-amylase, and Aspergillus niger glucamylase using N-acetylimidazole as the specific protein reagent. The changes in activity binding affinity (Δk_?1/k₊₁), and kinetic parameters (K_m,k₂) due to acetylation of the phenolic hydroxyl groups have been determined. Acetylation of each enzyme occurred by an “apparent” first-order reaction with a rate constant of 0.72–1.4 x 10^?1min^?1. Acetylation increased the apparent K_m (soluble starch as the substrate) for each enzyme (appreciably for alpha-amylase and glucamylase), whereas k² remained unchanged. Similarly, for each enzyme, the binding affinity for immobilised cyclohexa-amylose decreased appreciably, whereas the catalytic activity was reduced only to a small degree (and remained unchanged for beta-amylase). It is concluded that the tyrosine groups located in the active centre of each enzyme have a substrate-binding function.     

Synthesis of methyl 2-acetamido-2-deoxy-3-O-(β-d-galactopyranosyl)-α-d-galactopyranoside from a corresponding thioglycoside derivative

The title disaccharide glycoside was synthesized by halide ion-promoted glycosidation, using methanol and the disaccharide bromide derived from methyl 2-azido-3-O-(2,3,4,6-tetra-O-benzoyl--d-galactopyranosyl)-4,6-O-benzylidene-2-deoxy-1-thio--d-galactopyranoside. This derivative in turn was prepared by silver triflate-promoted condensation of monosaccharide derivatives.     

Synthesis of allyl and benzyl 4-O-(3,6-di-O-methyl-β-d-glucopyranosyl)-2,3-di-O-methyl-α-l-rhamnopyranoside

Condensation of 2,4-di-O-acetyl-3,6-di-O-methyl-α-d-glucopyranosyl bromide with either allyl or benzyl 2,4-di-O-methyl-α-l-rhamnopyranoside in the presence of mercuric cyanide, followed by O-deacetylation, gave the title oligosaccharides in excellent yields.

     

Use of 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide as a glycosyl donor: Synthesis of p-nitrophenyl 3-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-β-d-galactopyranoside

Acetolysis of methyl 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranoside afforded 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-1,2,4,6-tetra-O-acetyl-d-galactopyranose (2). Treatment of 2 in dichloromethane with hydrogen bromide in glacial acetic acid gave 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)- 2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide (3). The α configuration of 3 was indicated by its high, positive, specific rotation, and supported by its ¹H-n.m.r. spectrum. Reaction of 3 with Amberlyst A-26-p-nitrophenoxide resin in 1:4 dichloromethane-2-propanol furnished p-nitrophenyl 3-O-(2-acetamido-3,4,6- tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-β-d-galactopyranoside (7). Compound 7 was also obtained by the condensation (catalyzed by silver trifluoromethanesulfonate-2,4,6-trimethylpyridine) of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl bromide with p-nitrophenyl 2,4,6-tri-O-acetyl-β-d-galactopyranoside, followed by the usual deacylation-peracetylation procedure. O-Deacetylation of 7 in methanolic sodium methoxide furnished the title disaccharide (8). The structure of 8 was established by ¹³C-n.m.r. spectroscopy.     

Stereoselective Synthesis of 1- and 2-O-α-d-Cellotriosyl-3-deoxy-2(R)- and 2(S)-glycerols Related to Rhynchosporoside

The stereoselective synthesis of 1- and 2-O-α-d-cellotriosyl-3-deoxy-2(R)- and 2(S)-glycerols, which determined the structure of rhynchosporoside produced by Rhynchosporium secalis, and their phytotoxicity toward the host plant (Hordeum vulgare) are described in detail.     

Synthesis of 3-O-(2-acetamido-2-deoxy-3-O-β-d-galactopyranosyl-β-d-galactopyranosyl)-1,2-di-O-tetradecyl-sn-glycerol

Stereo- and regio-selective synthesis of 3-O-(2-acetamido-2-deoxy-3-O-β-d- galactopyranosyl-β-d-galactopyranosyl)-1,2-di-O-tetradecyl-sn-glycerol by use of 1,2-di-O-tetradecyl-3-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-galactopyranosyl)-sn-glycerol as a key intermediate is described.     

Synthesis and Antileishmanial Activity of 3-(α-Azolylbenzyl)indoles

The goal of the present study was to evaluate several azolyl-substituted indoles as new antileishmanial agents. Ten 3- (α -azolylbenzyl)indoles have been synthesized using Friedel-Crafts acylation as a key-step. All the target compounds were found to display high levels of activity when tested against Leishmania mexicana promastigotes in vitro. The most active compounds, showing an IC 50 <1 μM, were 5-bromo-1-ethyl-3-[(2,4-dichlorophenyl)(1 H -imidazol-1-yl)methyl]-1 H -indole 15 and its triazole analogue 17. Four representative compounds 15, 17, 22 and, 23 were also tested against intracellular amastigotes of L. mexicana using ketoconazole and meglumine antimoniate as reference compounds, the results of which are discussed.     

Synthesis of 3,6-di-O-acetyl-2-deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d-glucopyranosyl chloride

A lactosaminyl donor, 3,6-di-O-acetyl-2-deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d- glucopyranosyl chloride, was synthesized in 10 steps, starting from 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranose. Benzyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside was prepared by regioselective benzylation at the primary hydroxyl group by the stannyl method, and was used as a key intermediate.

     

Synthesis of 3-O-β-d-xylopyranosyl-l-serine (xylosylserine) andO-β-d-galactopyranosyl-(1-4)-O-β-d-xylopyranosyl-l-serine (galactosylxylosylserine) and use of the synthetic products for detection of galactosyltransferase I activity in rat liver

3-O-β-d-Xylopyranosyl-l-serine (xylosylserine) was synthesized by the following three-step procedure: 1) 2,3,4-tri-O-benzoyl-α-d-xylopyranosyl bromide (benzobromoxylose) was condensed withN-carbobenzoxy-l-serine benzyl ester using the silver triflate-collidine complex as promoter; 2) theN-carbobenzoxy and benzyl ester groups in the resultant glycoside were cleaved by transfer hydrogenation with palladium black as catalyst and ammonium formate as hydrogen donor; and 3) the benzoyl groups were removed with methanolic ammonia. Xylosylserine was obtained in an overall yield of 70%. O-β-d-Galactopyranosyl-(1-4)-O-β-d-xylopyranosyl-(1-3)-l-serine (galactosylxylosylserine) was also synthesized by this methodology and was characterized by 2-dimensional (2D) NMR spectroscopy techniques. The two serine glycosides (xylosylserine and galactosylxylosylserine) were used in detection and partial purification of galactosyltransferase I (UDP-d-galactose:d-xylose galactosyltransferase) from adult rat liver.     

Synthesis of five nona-β-(1→6)-d-glucosamines with various patterns of N-acetylation corresponding to the fragments of exopolysaccharide of Staphylococcus aureus

A series of five 3-acetamidopropyl β-glycosides of nona-β-(1→6)-glucosamines containing two N-acetylglucosamine residues separated by a different number of glucosamine units with free amino groups have been synthesized using a convergent blockwise approach. Oxazoline glycosylation was used to introduce N-acetylglucosamine residues. These nonasaccharides are structurally related to the poly-N-acetylglucosamine (PNAG) extracellular polysaccharide of Staphylococcus aureus and can be used as models for biochemical and immunological studies.     

Synthesis of benzyl 2-acetamido-2-deoxy-3-O-β-d-fucopyranosyl-α-d-galactopyranoside and benzyl 2-acetamido-6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2-deoxy-3-O-β-d-fucopyranosyl-α-d-galactopyranoside

Condensation of benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-d-galactopyranoside with 2,3,4-tri-O-acetyl-α-d-fucopyranosyl bromide in 1:1 nitromethane-benzene, in the presence of powdered mercuric cyanide, afforded benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4-tri-O-acetyl-β-d-fucopyranosyl)-α-d-galactopyranoside (3). Cleavage of the benzylidene group of 3 with hot, 60% aqueous acetic acid afforded diol 4, which, on deacetylation, furnished the disaccharide 5. Condensation of diol 4 with 2-methyl-(3,4,6-tri-O-acetyl-1,2-di-deoxy-α-d-glucopyrano)-[2,1-d]-2-oxazoline in 1,2-dichloroethane afforded the trisaccharide derivative (7). Deacetylation of 7 with Amberlyst A-26 (OH^?) anion-exchange resin in methanol gave the title trisaccharide (8). The structures of 5 and 8 were confirmed by ¹³C-n.m.r. spectroscopy.     

Synthesis of 8-Bromo- and 8-Azido-2′-deoxyadenosine-5′-O-(1-thiotriphosphate)

Abstract

Treatment of 3′-O-methoxyacetylated 8-bromo-2′-deoxyadenosine (5), with a twofold excess of salicyl phosphorochloridite (6), and subsequent reaction with bis(tri-n-butylammonium) pyrophosphate and oxidation with sulfur followed by removal of the protecting group gives predominantly 8-bromo-2′-deoxyadenosine-5′-O-(1-thiotriphosphate) (7), and minor amounts of the corresponding brominated monothiophosphate. Alternatively, the photoreactive dATP analog 8-azido-2′-deoxyadenosine-5′-O-(1-thiotriphosphate) (11), is obtained by phosphorylation of unprotected 8-azido-2′-deoxyadenosine (9) with a 1.8 molar equivalent excess of thiophosphoryl chloride and bis(tri-n-butylammonium) pyrophosphate. A protection of the nucleobase 6-amino group is not required. The photoaffinity labeling reagent 11, was characterized by ³¹P-NMR and ion-spray mass spectroscopy and its photolysis upon long wavelength UV irradiation was studied. Both α-thioderivatives of 2′-deoxyadenosine triphosphates can be incorporated into plasmid DNA by T7 DNA polymerase. Thus, they can be used for interference studies of protein binding and for cross-linking with amino acids in protein-nucleic acid-complexes.     

Synthesis of 5-Fluoro-1-(3-O-benzoyl-4, 6-dideoxy- β-L-GLYCERO-hex-3-enopyranos-2-ulosyl)uracil

Abstract

Synthesis of the title compound, an unsaturated ketohexo-pyranosyl nucleoside of 5-fluorouracil is reported. It was prepared by oxidation of the corresponding dibenzoylhexopyranosyl nucleoside with pyridinium dichromate/molecular sieves system.     

A Convenient Method for the Synthesis of 2-(β-D-Glycopyranosylthio) Pyridines

Abstract

Treatment of piperidinium salts of dihydropyridinethiolates 3 with glycosyl bromides 4 in dry acetone provides a convenient and high yielding synthesis of 1,4-dihydro-3-cyanopyridine thioglycosides 5. The structures of 5 were confirmed by oxidation as well as by ¹H NMR and ¹³C NMR spectral analysis.