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.     

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.     

Synthesis of 2,3-unsaturated glycosides via metal-free Ferrier reaction

Hexafluoroisopropanol (HFIP) is explored as an effective medium for the synthesis of 2,3-unsaturated glycosides through allylic rearrangement of 3,4,6-tri-O-acetyl glucal. This metal-free, exclusively solvent-promoted Ferrier glycosylation, affords products in good to excellent yields and with good α-selectivity.     

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.     

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.     

Sm(OTf)3 as a highly efficient catalyst for the synthesis of 2,3-unsaturated O- and S-pyranosides from glycals and the temperature-dependent formation of 4-O-acetyl-6-deoxy-2,3-unsaturated S-pyranosides and 4-O-acetyl-6-deoxy-3-alkylthio glycals

By using Sm(OTf)₃ as the catalyst, synthesis of 2,3-unsaturated-glycosides has been performed. A series of 2,3-unsaturated glycosides were obtained from 3,4,6-tri-O-acetyl–d-glucal or 3,4-di-O-acetyl-l-rhamnal under mild reaction conditions in good yield and high anomeric selectivity. It was found that under certain conditions, reaction of 3,4-di-O-acetyl-l-rhamnal with thiol leads to temperature-dependent formation of C-1-S and C-3-S product. A temperature-dependent profile of the yield of these two products is given.     

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.     

Synthesis of flavonoid 2-deoxyglucosides via the Mitsunobu reaction

The Mitsunobu reaction of flavonoids and 3,4,6-tri-O-acetyl-2-deoxy-d-glucopyranose or 3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranose is a very effective method for the stereoselective synthesis of flavonoid 2-deoxyglucosides. Since there is no C2 substituent on the sugar moieties, the observed α- or β-stereoselectivity was mainly controlled by the (acetyl or benzyl) protecting groups. Possible mechanistic insights are offered to explain the dual stereoselectivity.     

Regioselective monohydrolysis of per-O-acetylated-1-substituted-β-glucopyranosides catalyzed by immobilized lipases

The regioselective monohydrolysis of different peracetylated-β-glucopyranosides in aqueous media using immobilized preparations of three different lipases—those from Aspergillus niger (ANL), Candida rugose (CRL) and Candida antarctica B (CAL-B)—has been studied. Three very different immobilization strategies—covalent attachment, anionic exchange and interfacial activation on a hydrophobic support—were employed for each lipase. The role of the immobilization strategy and the effect of the presence of different moieties in the anomeric position of the substrate on the hydrolytic activities, specificities and regioselectivities of the lipases were investigated. For example, the PEI-ANL preparation exhibited 800 times higher activity than the octyl-ANL in the hydrolysis of 2-acetamido-2-deoxy-1-(4-nitrophenyl)-3,4,6-tri-O-acetyl-β-d-glucopyranoside—producing 4-OH derivative in 18% yield—whereas the octyl-ANL was five times more active than the PEI-ANL in the hydrolysis of 1-(4-nitrophenyl)-2,3,4-tri-O-acetyl-β-d-xylopyranoside, producing 4-OH monohydroxy product in >99% yield.The octyl-CRL preparation hydrolyzed regioselectively 3,4,6-tri-O-acetyl-glucal in position 6 in 68% yield while the PEI-CRL produced the 3-OH product in 11% yield, although with moderate specificity. The CNBr-CAL-B hydrolyzed specifically and regioselectively the glucal producing the 3-OH product in >99% yield.     

Stereoselective total synthesis of cryptopyranmoscatone A1

The first total synthesis of cryptopyranmoscatone A1 isolated from Cryptocarya moschata has been accomplished from 3,4,6-tri-O-acetyl-d-glucal. In addition to the RCM and cross-metathesis (CM) reactions, the synthesis features a highly diastereoselective Brown’s allylation reaction and sets the absolute stereochemistry of the natural product.     

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.     

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.     

Microwave‐Enhanced Ferrier Reaction: A Facile Synthesis of 2,3‐Unsaturated‐O‐Glycosides Under Solvent‐Free Conditions

A variety of 2,3‐unsaturated‐O‐glycosides have been prepared by the Ferrier rearrangement of acetyl protected glycals under microwave irradiation using silica gel as an acid catalyst. Environmental friendliness, high yields, and short reaction times are the key features of this method. Furthermore, the method was applicable not only to the Ferrier reaction of 3,4,6‐tri‐O‐acetyl glucal and 3,4,6‐tri‐O‐acetyl galactal but also to the Ferrier reaction of 3,4‐di‐O‐acetyl arabinal.     

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.     

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.     

Total synthesis of cryptopyranmoscatone B1 from 3,4,6-tri-O-acetyl-d-glucal

The first stereoselective total synthesis of the natural cryptopyranmoscatone B1 has been accomplished from 3,4,6-tri-O-acetyl-d-glucal. In addition to the double cross-metathesis reaction, a tandem nucleophilic addition-diastereoselective reduction of an in situ generated oxocarbenium cation have been used as key steps to assemble the glycoside moiety of the target molecule.     

Synthesis of propargyl C-glycosides using allenyltributylstannane

Protected propargyl C-glycosides have been prepared by activation of the anomeric centres of 2,3,4,6-tetra-O-benzyl- derivatives of d-glucose and d-galactose, followed by treatment with allenyltributylstannane in the presence of Lewis-acid. Activation was by formation of the anomeric acetates, trichloroacetimidates or fluorides; boron trifluoride etherate and trimethylsilyl trifluoromethanesulfonate were particularly effective Lewis-acids. Attempts to perform similar reactions on 1,2,3,4,6-penta-O-acetyl-d-glucose led to participation by the C-2 acetate group and formation of 3,4,6-tri-O-acetyl-1,2-O-[1-(prop-2-ynyl)ethylidene]-α-d-glucopyranose.     

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.     

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.     

Stereoselective synthesis of safingol and its natural stereoisomer from d-glycals

Efficient and convenient syntheses of (2S,3S)-safingol and its natural (2S,3R)-isomer have been developed from 3,4,6-tri-O-benzyl glycals. The key step is the one-pot reduction of an azide, saturation of the double bonds and debenzylation under catalytic hydrogenation.