Synthesis and Antitubercular and Antibacterial Activities of Triethylammonium 2-Acetamido-3,4,6-tri-<Emphasis Type="Italic">O</Emphasis>-acetyl-2-deoxy-D-glucopyranosyl Decyl Phosphate

Phosphorylation of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucose at the anomeric hydroxy group gave previously unknown triethylammonium 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucopyranosyl phosphonate, and successive treatment of the latter with decan-1-ol and aqueous iodine afforded triethylammonium 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl phosphate.     

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.     

Y(OTf)3 as a highly efficient catalyst in Ferrier Rearrangement for the synthesis of O- and S-2,3-unsaturated glycopyranosides

By using Y(OTf)₃ as the catalyst, a series of 2,3-unsaturated-glucosides have been synthesized from 3,4,6-tri-O-acetyl-d-glucal, 3,4-di-O-acetyl-l-rhamnal, and 3,4,6-tri-O-benzyl-d-glucal under mild reaction conditions in good yields with high anomeric selectivities. It was found that, in this reaction, 3,4,6-tri-O-benzyl-d-glucal behaved differently from the other two glucals when it was reacted with phenol, O-benzyl glucoside instead of O-phenyl glucoside formed as the sole product. An explanation is given for this phenomenon.     

Scope of AuCl3 in the activation of per-O-acetylglycals

Gold(III)chloride in catalytic amounts activates 3,4,6-tri-O-acetyl-d-glucal, 3,4,6-tri-O-acetyl-d-galactal, and 3,4-di-O-acetyl-l-rhamnal efficiently. The activated species can be employed in the Ferrier reaction with different nucleophiles at ambient conditions. Attempts have been made to make β-anomer of the Ferrier product from anomeric-O-propargylated Ferrier product.     

An efficient stereoselective synthesis of enantiomerically pure aziridine derivatives of allyl β-d-glucopyranosides asymmetrically induced by a glucide moiety

The enantiomerically pure title aziridines were obtained by regioselective azidolysis of the 2′,3′-epoxy derivatives of allyl 3,4,6-tri-O-benzyl-β-d-glucopyranosides, followed by cyclization of the corresponding azido alcohols by means of the PPh₃ protocol. Enantiomerically pure starting epoxides were prepared by epoxidation of the corresponding allyl 3,4,6-tri-O-benzyl-β-d-glucopyranosides asymmetrically induced by a glucide moiety.     

Preparation of new amide-linked pseudodisaccharides by the carboxymethylglycoside lactone (CMGL) strategy

6-Aminodeoxy sugars react with carboxymethyl 3,4,6-tri-O-acetyl-α-d-glucopyranoside 2-O-lactone (α-CMGL) to provide the corresponding new amide-linked glucose/glucose or glucose/galactose pseudodisaccharides in good yields. The strategy is extended to the synthesis of an amide-linked sugar/nucleoside adduct.     

Synthesis Of Ligands Related To The O-Specific Antigen Of Shigella Dysenteriae Type 1.

Abstract

Stereoselective α-D-galactosylation at the position 3 of 4,6-O-substituted derivatives of methyl 2-acetamido-2-deoxy-α-D-glucopyranoside is described. Glycosyl chlorides derived from 3,4,6-tri-O-acetyl-2-O-benzyl- and 2-O-(4-methoxybenzyl)-D-galactopyranose have been used as glycosyl donors. Methyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (27) and methyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (31) have been prepared.     

Hafinium (IV) promoted synthesis of 2,3-unsaturated N- and C-pseudoglycosides via Type I Ferrier Rearrangement

By using Hf(OTf)₄ as the catalyst, a series of 2,3-N- and C-unsaturated-glucosides have been synthesized from 3,4,6-tri-O-acetyl-d-glucal, 2,4,6-tri-O-benzyl-d-glucal and ((2R,3S)-3-acetoxy-2,3-dihydrofuran-2-yl)methyl acetate under mild reaction conditions in good yields with high anomeric selectivities.     

Synthese des substances de groupe sanguin—IV : Synthese du 2-acetamido-2-desoxy-4-O-[2-O-(α-l-fucopyranosyl)-β-d-galactopyranosyl]-d-glucopyranose,porteur de la specificite H

The synthesis of a H blood group specific trisaccharide was performed by using benzyl ethers as temporary blocking groups for hydroxylic functions. Benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-d- glucopyranoside was glycosylated by 3,4,6-tri-O-benzyl-1,2-O-benzyl-1,2-O-(tert-butoxyethylidene)-α-d-galactopyranose; after O-deacetylation, glycosylation by 2,3,4-tri-O-benzyl-α-l-fucopyranosyl bromide, and hydrogenolysis, 2-acetamido-2-deoxy-4-O-[2-O-(α-l-fucopyranosyl)-β-d-galactopyranosyl]-d-glucopyranose is obtained.     

SYNTHESIS OF NEW OXAMIDE DERIVATIVES OF D-GLUCOSAMINE AND ALIPHATIC OR AROMATIC AMINES

New oxamides, derivatives of D-glucosamine and aliphatic or aromatic amines were prepared by acylation of methyl 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-α- or -β-D-glucopyranoside (1c or 1d) with oxalyl chloride, followed by reaction with amine. The reaction was assumed to proceed by the intermediate of N-carbomethoxy N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α or β-D-glucopyranosid-2-yl) oxamic acid chloride which reacted with amines, and afforded N-acetyl, N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (5–7), and N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (8–13).     

Glucose ferrocenyl-oxazolines: Coordination behavior toward [Pd(η-allyl)Cl]2 studied by ESI-MS

Several new oxazolin-2-yl-substituted ferrocenes based on 2-amino-2-deoxy-α-d-glucose were synthesized via the corresponding amides followed by closing the oxazoline-ring with SnCl₄.Coordination properties of representatives of the group of mono- and bis-oxazolinyl ferrocenes, 2-ferrocenyl-4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazoline and 1,1′-bis{4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazolin-2-yl}ferrocene, respectively, toward [Pd(η³-allyl)Cl]₂ were investigated by electrospray ionization mass spectrometry in positive ion mode and by MS/MS technique.With the monooxazoline derivative mainly a 1:1 complex with the Pd-moiety was found in the mass spectrum while the bisoxazoline yields a stoichiometry of 2:1 (oxazoline:Pd). The latter result is attributed to steric hindrance of the coordination of a second Pd-moiety to the bulky bisoxazolinyl-ferrocene.In the case of 1,1′-bis{4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazolin-2-yl}ferrocene 9 overlapping of two signals in the m/z range from 955-965 was found which can be assigned to the singly charged adduct [C₃₆H₄₀FeN₂O₁₆ + Pd(η³-C₃H₅)]⁺ and a doubly charged Pd-ligand cluster with the general formula Pd₂[L(9)]₂.In addition, the molecular structure of 1,1′-bis{4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazolin-2-yl}ferrocene was determined by X-ray diffraction analysis.     

Stereoselective Glycosidic Coupling Reactions of Fully Benzylated 1,2-Anhydro Sugars with N-Tosyl- or N-Benzyloxycarbonyl-l-serine Methyl Ester

Abstract

The glycosidic coupling reaction of 1,2-anhydro-3,4,6-tri-O-benzyl-β-d-mannopyranose (7), 1,2-anhydro-3,4,6-tri-O-benzyl-α-d-galactopyranose (21), and 1,2-anhydro-3,4-di-O-benzyl-α-d-xylopyranose (18) with N-tosyl- (10) or N-benzyloxycarbonyl- (11) L-serine methyl ester provides a new stereocontrolled synthesis of 1,2-trans linked glycopeptides. The 1,2-anhydro sugars are shown to react smoothyl with 10 or 11 in the presence of Lewis acid (ZnCl₂ or AgOTf) as well as powdered 4A molecular sieves in CH₂Cl₂ at room temperature to afford glycosyl serine derivatives with high stereoselectivity and high yield in less than 30 min. An improved method using 2-O-acetyl-3,4,6-tri-O-benzyl-α-d-mannopyranosyl chloride (6) as the key intermediate for ring closure was applied for the synthesis of 1,2-anhydro-3,4,6-tri-O-benzyl-β-d-mannopyranose.     

Syntheses of l-glucosamine donors for 1,2-trans-glycosylation reactions

Two new l-glucosamine donors, that is pent-4-enyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-β-l-glucopyranoside 16 and ethyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-1-thio-β-l-glucopyranoside 21 were prepared in 12 steps from l-arabinose. The reaction pathway uses 3,4,6-tri-O-acetyl-l-glucal 5, and then 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-α-l-mannopyranosyl azide 8 as intermediates. The latter, together with donors 16 and 21, were used for preparing l-glucosamine neoglycolipids.     

A synthesis of 2-fluoroglucal derivatives

3,4,6-Tri-O-methyl-d-glucal, readily prepared from 3,4,6-tri-O-acetyl-d-glucal, undergoes lithiation at −78 °C in THF with t-BuLi to afford a vinyl carbanion, which can be trapped with electrophiles in moderate overall yields. The palladium coupling and Dötz-type reactions of these intermediates are also described.     

A synthesis of 2-β-D-ribofuranosyl-4-selenazolecarboxamide (selenazofurin) and certain N-substituted amide derivatives suitable for large scale syntheses

A new process suitable for large scale synthesis of the antitumor-antiviral agent, 2-β-D-ribofuranosyl-4-selenazolecarboxamide (selenazofurin, 1 ), has been developed. Thus, 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose ( 3 ) was converted with cyanotrimethylsilane and stannic chloride to the crystalline 2,5-anhydro-3,4,6-tri-O-benzoyl-β-D-allononitrile ( 4 ) without chromatography. Cyanosugar 4 in ethanol was treated with hydrogen selenide gas to afford stereospecifically the unstable 2,5-anhydro-3,4,6-tri-O-benzoyl-β-D-allonoselenoamide ( 5 ) which was converted in situ by ethyl bromopyruvate to the stable ethyl 2-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-4-selenazolecarboxylate ( 6). Selenazole ethyl ester 6 was deprotected with sodium methoxide affording methyl 2-β-D-ribofuranosyl-4-selenazolecarboxylate ( 7 ) which was aminated with ammonia to provide selenazofurin ( 1 ) or with other amines to provide N-substituted selenazofurin amides.     

An expedient route for the practical synthesis of pachastrissamine (jaspine B) starting from 3,4,6-tri-O-benzyl-d-galactal

A practically efficient stereoselective synthesis of pachastrissamine (jaspine B) is described starting from 3,4,6-tri-O-benzyl-d-galactal in eight steps and 11% overall yield.     

The anomeric Pudovik rearrangement

The O,O-dibenzyl-S-glycosyl phosphothioite derived from 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-α-d-glucopyranose rearranges under the influence of triethylborane and air to provide the corresponding 1-C-pyranosyl-O,O-dibenzylphosphonothioate, a new type of carbohydrate derivative. The isomeric beta phosphothioite is compared, and evidence of a radical chain mechanism for the Pudovik rearrangement is presented.     

ZnCl2-catalyzed Ferrier reaction; synthesis of 2,3-unsaturated 1-O-glucopyranosides of allylic, benzylic and tertiary alcohols

Tertiary, allylic and benzylic alcohols react with 3,4,6-tri-O-acetyl-d-glucal in dichloromethane at 25°C in the presence of ZnCl₂ to afford the corresponding 2,3-unsaturated-1-O-glucopyranoside acetates in 65-91% yields, with selective formation of the α-anomer.     

A mild and efficient synthetic protocol for Ferrier azaglycosylation promoted by ZnCl2/Al2O3

An improved method for the Ferrier sulfonamidoglycosylation of tri-O-acetyl-d-glucal with different N-nucleophiles has been developed. ZnCl₂ impregnated on activated alumina acts as an excellent reagent system for the conversion of 3,4,6-tri-O-acetyl-d-glucal into 2,3-unsaturated-N-pseudoglycals with good yields and preferential α-anomeric selectivity.     

N-Dimethylphosphoryl-protected glucosamine trichloroacetimidate as an effective glycosylation donor

Glycosylation of a variety of alcohols with 3,4,6-tri-O-acetyl-2-N-dimethylphosphoryl-2-deoxy-α-d-glucopyranosyl trichloroacetimidate as a glycosyl donor provided the corresponding coupled products in high yields and good β-selectivity. N-Dimethylphosphoryl-protection stayed stable under acidic and basic conditions for further elaboration of the glucosamine-containing oligosaccharides.