Direct glycosylation with anomeric hydroxy sugars by activation with 3-fluorophthalic anhydride and trifluoromethanesulfonic anhydride

An efficient and direct one-pot glycosylation method using anomeric hydroxy sugars as glycosyl donors, employing 3-fluorophthalic anhydride and triflic anhydride as activating agents, has been developed. The present glycosylation utilizing 3-fluorophthalic anhydride resulted in few to no undesired self-condensed esters than the glycosylation using phthalic anhydride. Intermediates in the present glycosylation were identified by an NMR study.     

Lewis acids as α-directing additives in glycosylations by using 2,3-O-carbonate-protected glucose and galactose thioglycoside donors based on preactivation protocol

Catalytic or stoichiometric amounts of Lewis acids were found to be very effective α-directing additives in the stereoselective glycosylations of diverse 2,3-O-carbonate-protected glucose and galactose thioglycoside donors by preactivation protocol. The poor stereoselectivities of 4,6-di-O-acetyl-2,3-O-carbonate protected thioglycoside donors in glycosyl coupling reactions were greatly improved, and excellent α-stereoselectivities were achieved by the addition of 0.2 equiv of BF(3)·OEt(2). On the other hand, the β-selectivities of 4,6-di-O-benzyl-2,3-O-carbonate-protected thioglucoside donor toward glycosylations were reversed completely to the α-selectivities by the use of 1 equiv of SnCl(4), making the stereoselectivity controllable. Furthermore, the poor stereoselectivities of 4,6-di-O-benzyl-2,3-O-carbonate-protected thiogalactoside donor in glycosylations were also improved by using SnCl(4) as additive.     

Ethyl 2-acetamido-4,6-di-O-benzyl-2,3-N,O-carbonyl-2-deoxy-1-thio-beta-D-glycopyranoside as a versatile GlcNAc donor

The title donor, ethyl 2-acetamido-4,6-di-O-benzyl-2,3-N,O-carbonyl-2-deoxy-1-thio-beta-D-glycopyranoside, is shown to be an excellent glycosyl donor giving immediate and efficient access to variant GlcNAc-containing oligosaccharides.     

Highly diastereoselective alpha-mannopyranosylation in the absence of participating protecting groups

S-Phenyl 2,6-di-O-benzyl-3,4-O-(2',3'-dimethoxybutane-2', 3'-diyl)-1-thia-alpha-D-mannopyranoside and its sulfoxide, following activation at -78 degrees C with benzenesulfenyl triflate or triflic anhydride, respectively, provide the corresponding alpha-mannosyl triflate as demonstrated by NMR spectroscopy. On addition of an acceptor alcohol alpha-mannosides are then formed. Similarly, S-phenyl 2,3-O-carbonyl-4, 6-O-benzylidene-1-thia-alpha-D-mannopyranoside and ethyl 3-O-benzoyl-4, 6-O-benzylidene-2-O-(tert-butyldimethylsilyl)-1-thia-alpha-D-mannopyr anoside both provide alpha-mannosides on activation with benzenesulfenyl triflate followed by addition of an alcohol. These results stand in direct contrast to the highly beta-selective couplings of comparable glycosylations with 2,3-di-O-benzyl-4, 6-O-benzylidene protected mannosyl donors and draw attention to the subtle interplay of reactivity and structure in carbohydrate chemistry.     

Armed-disarmed effect of remote protecting groups on the glycosylation reaction of 2,3-dideoxyglycosyl donors

The armed-disarmed effect of remote protecting groups at the C-4 and/or C-6 position(s) on the glycosylation reactions of 2,3-dideoxyglycosyl donors was investigated. It was found that under various glycosylation conditions, 4- or 6-O-Bn 2,3-dideoxyglycosyl donors were much more reactive than the corresponding 4,6-di-O-Bz 2,3-dideoxyglycosyl donors. Based on these results, an effective and chemoselective glycosylation reaction using 4,6-di-O-Bn glycosyl acetate and 4-OH-6-O-Bz glycosyl acetate was realized, producing a 2,3-dideoxydisaccharide in good yield with high α-stereoselectivity.     

Sequential one-pot glycosylation with glycosyl N-trichloroacetylcarbamate and trichloroacetate including dehydrative approach using 1-hydroxy sugars

An efficient sequential one-pot glycosylation has been developed with glycosyl trichlorocarbamate and trichloroacetate activated by the same Lewis acid and enabled by a change in reaction temperature. The αα-selective glycosylation was achieved using glucose, galactose, and mannose substrates after investigation into the reactivities of the two types of glycosyl donors. Sequential one-pot dehydrative glycosylation, including in situ preparation of glycosyl donors followed by generation of two glycosyl bonds, provided three types of trisaccharide.     

One-pot synthesis of sialo-containing glycosyl amino acids by use of an N-trichloroethoxycarbonyl-beta-thiophenyl sialoside

We describe an efficient synthesis of 2,6- and 2,3-sialyl T antigens linked to serine in a one-pot glycosylation. We first investigated the glycosidation of thiosialosides by varying the N-protecting group. Modification of the C-5 amino group of beta-thiosialosides into the N-9-fluorenylmethoxycarbonyl, N-2,2,2-trichloroethoxycarbonyl (N-Troc), and N-trichloroacetyl derivatives enhanced the reactivity of these compounds towards glycosidation. Addition of a minimum amount of 3 A molecular sieves was also effective in improving the yield of alpha-linked sialosides. Next, we conducted one-pot syntheses of the glycosyl amino acids by using the N-Troc sialyl donor. The N-Troc derivative can be converted into the N-acetyl derivative without racemization of the amino acids. Branched-type one-pot glycosylation, initiated by regioselective glycosylation of the 3,6-dihydroxy galactoside with the N-Troc-beta-thiophenyl sialoside, provided the protected 2,6-sialyl T antigen in good yield. Linear-type one-pot glycosylation, initiated by chemoselective glycosylation of galactosyl fluoride with the N-Troc-beta-thiophenyl sialoside, afforded the protected 2,3-sialyl T antigen in excellent yield. Both protected glycosyl amino acids were converted into the fully deprotected 2,6- and 2,3-sialyl T antigens linked to serine in good yields.     

Stereoselectivity investigation on glycosylation of oxazolidinone protected 2-amino-2-deoxy-d-glucose donors based on pre-activation protocol

Diverse 2,3-oxazolidinone protected 2-amino-2-deoxy-d-glucose thioglycosides were prepared and studied as glycosyl donors at low temperature by BSM/Tf₂O pre-activation protocol before the addition of glycosyl acceptors. The stereochemistry outcomes of a series of glycosylations were investigated. Different stereoselectivities of the coupling reactions were obtained, arising from the different protecting groups in the oxazolidinone donors. 4,6-Di-O-benzyl-N-benzyl-oxazolidinone protected thioglycoside donor 1c underwent glycosylation with general β-anomeric selectivity and the stereoselectivity could be also affected by glycosylation conditions.     

Direct stereoselective synthesis of beta-thiomannosides

A highly diastereoselective synthesis of beta-thiomannopyranosides is described in which S-phenyl 2,3-di-O-benzyl-4, 6-O-benzylidene-1-deoxy-1-thia-alpha-D-mannopyranoside S-oxide is treated with triflic anhydride and 2, 6-di-tert-butyl-4-methylpyridine in CH(2)Cl(2) at -78 degrees C leading to the formation of an intermediate alpha-mannosyl triflate. Addition of primary, secondary, or tertiary thiols then leads to the beta-thiomannosides, by an S(N)2-like displacement, in good yield and with excellent stereoselectivity. Deprotection is achieved either by Birch reduction or by Zemplen deacetylation, of the acetyl protected aglycons, followed by hydrogenolysis over Pearlman's catalyst. The assignment of configuration of the beta-thiomannopyranosides is discussed in terms of the chemical shift of the mannose H5 resonance and the (1)J(CH) of the mannose anomeric carbon.     

Stereoselective 1,2-cis glycosylation of 2-O-allyl protected thioglycosides

The technique of intramolecular aglycon delivery (IAD), whereby a glycosyl acceptor is temporarily appended to a hydroxyl group of a glycosyl donor is an attractive method that can allow the synthesis of 1,2-cis glycosides in an entirely stereoselective fashion. 2-O-Allyl protected thioglycoside donors are excellent substrates for IAD, and may be glycosylated stereoselectively through a three-step reaction sequence. This sequence consists of quantitative yielding allyl bond isomerisation, to produce vinyl ethers that can then undergo N-iodosuccinimide mediated tethering of the desired glycosyl acceptor, and subsequent intramolecular glycosylation, to yield either alpha-glucosides or beta-mannosides accordingly. Although attempted one-pot tethering and glycosylation is hampered by competitive intermolecular reaction with excess glycosyl acceptor, this problem can be simply overcome by the use of excess glycosyl donor. Allyl mediated IAD is a widely applicable practical alternative to other IAD approaches for the synthesis of beta-mannosides, that is equally applicable for alpha-gluco linkages. It is advantageous in terms of both simplicity of application and yield, and in addition has no requirement for cyclic 4,6-protection of the glycosyl donor.     

2-(Hydroxycarbonyl)benzyl glycosides: a novel type of glycosyl donors for highly efficient beta-mannopyranosylation and oligosaccharide synthesis by latent-active glycosylation

2-(Benzyloxycarbonyl)benzyl (BCB) glycosides were prepared by coupling of the corresponding tetraacetylglycosyl bromides and benzyl 2-(hydroxymethyl)benzoate. The BCB glycosides were converted almost quantitatively into the corresponding 2-(hydroxycarbonyl)benzyl (HCB) glycosides by selective hydrogenolysis of the benzyl ester functionality without affecting the benzylidene acetal and the benzyl ether. Treatment of the HCB 4,6-O-benzylidenemannopyranoside 4 with triflic anhydride in the presence of di-tert-butylmethylpyridine and subsequent addition of the glycosyl acceptor having a primary hydroxyl group afforded exclusively the disaccharide of the beta-mannopyranosyl linkage. Glycosylation of the compound 4 with secondary and tertiary alcohols also provided beta-mannopyranosides as the major products. Glycosylation of the HCB 4,6-O-cyclohexylidenemannoside 5 with primary alcohols was also highly beta-selective, and the HCB 2,3-O-cyclohexylidenemannoside 6 exhibited the moderate beta-selectivity. On the other hand, unlike the HCB mannosides, the HCB 4,6-O-benzylideneglucoside 7 gave exclusively the disaccharides of the alpha-glycopyranosyl linkage in the glycosylation with primary alcohols. The latent BCB-disaccharide 23, which was obtained from the HCB mannoside 4 as the donor and the BCB glucoside 12 as the acceptor by the present glycosylation method, was converted into the active HCB-disaccharide 39 by selective hydrogenolysis. Repetitive glycosylation of the donor 39 with the same acceptor 12 afforded the BCB-trisaccharide 40. Other BCB-trisaccharides 42 and 46 were also efficiently synthesized by employing the present methodology.     

A rapid, one-pot, four-component route to 2H-indazolo[2,1-b]phthalazine-triones

A new, efficient, and environmentally benign protocol for the one-pot, four-component synthesis of 2,2-dimethyl-13-phenyl-2,3-dihydro-1H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione by condensation of phthalic anhydride, hydrazinium hydroxide, aromatic aldehydes, and dimedone catalyzed by Ce(SO₄)₂·4H₂O as an ecofriendly catalyst with high catalytic activity and reusability at 125 °C under solvent-free conditions is reported. The reaction proceeds to completion within 5-10 min in 71-95% yield. To the best of our knowledge, this new procedure provides the first example of an efficient synthetic method for 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione via a four-component reaction.     

Preparation of poly(glycidylmethacrylate‐divinylbenzene) weak acid cation exchange stationary phases with succinic anhydride,phthalic anhydride,and maleic anhydride for ion chromatography

In this work, poly(glycidylmethacrylate‐divinylbenzene) microspheres were prepared and applied for the preparation of weak acid cation exchange stationary phases. Succinic anhydride, phthalic anhydride, and maleic anhydride were selected as carboxylation reagents to prepare three weak acid cation exchangers by direct chemical derivatization reaction without solvent or catalyst. The diameters and dispersity of the microspheres were characterized by scanning electron microscopy; the amount of accessible epoxy groups and mechanical stability were also measured. The weak acid cation exchangers were characterized by Fourier transform infrared spectroscopy; the content of carboxyl groups was measured by traditional acid base titration method. The chromatographic properties were characterized and compared by separating alkali, alkaline earth metal ions and ammonium and polar amines. The separation properties enhanced in the order of succinic anhydride, phthalic anhydride, and maleic anhydride modified poly(glycidylmethacrylate‐divinylbenzene) cation exchangers.     

Novel one-pot multicomponent synthesis of (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-dione derivatives

Abstract

An expeditious, one-pot multicomponent reaction has been developed for the synthesis of (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-dione derivatives. Condensation of 4-amino-5-hydrazino-4H-1,2,4-triazole-3-thiol with phthalic anhydride and aromatic aldehyde afforded the (E)-2-(benzylideneamino)-5-mercapto-4H-1,2,4-triazol-3-yl)-2,3-dihydrophthalazine-1,4-diones in acetic acid medium with excellent yields. All the synthesized compounds were characterized by their analytical and spectral data.     

Au/FeOx-TiO2 as an efficient catalyst for the selective hydrogenation of phthalic anhydride to phthalide

<正>Au/FeO_x-TiO_2,prepared by deposition-precipitation method,is an efficient and stable catalyst for the liquid phase selective hydrogenation of phthalic anhydride to phthalide under mild reaction conditions.     

Mechanism of phthalic anhydride formation in the oxidation of n-pentane on a vanadium-phosphorus oxide catalyst

The reaction paths of product formation in the partial oxidation of n-pentane on vanadium-phosphorus oxide (VPO) and VPO-Bi catalysts are considered. The condensed products of n-pentane oxidation were analyzed by chromatography-mass spectrometry, and the presence of C₄ rather than C₅ unsaturated hydrocarbons was detected. It was found that the concentration of phthalic anhydride in the products increased upon the addition of C₄ olefins and butadiene to the n-pentane-air reaction mixture. With the use of a system with two in-series reactors, it was found that the addition of butadiene to a flow of n-butane oxidation products (maleic anhydride, CO, and CO₂) resulted in the formation of phthalic anhydride. The oxidation of 1-butanol was studied, and butene and butadiene were found to be the primary products of reaction; at a higher temperature, maleic anhydride and then phthalic anhydride were formed. The experimental results supported the reaction scheme according to which the activation of n-pentane occurred with the elimination of a methyl group and the formation of C₄ unsaturated hydrocarbons. The oxidation of these latter led to the formation of maleic anhydride. The Diels-Alder reaction between maleic anhydride and C₄ unsaturated hydrocarbons is the main path of phthalic anhydride formation.     

On the influence of the C2-O2 and C3-O3 bonds in 4,6-O-benzylidene-directed beta-mannopyranosylation and alpha-glucopyranosylation

The synthesis of 4,6-O-benzylidene-protected 2-deoxyarabino-, 3-deoxyarabino-, and 3-deoxyribothioglycosides is described and their glycosylation reactions, with activation by either 1-benzenesulfinyl piperidine/trifluoromethansulfonic anhydride or diphenyl sulfoxide/trifluoromethanesulfonic anhydride, studied. In contrast to the corresponding 4,6-O-benzylidene-protected glucosyl and mannosyl donors, which are alpha- and beta-selective, respectively, poor diastereoselectivity is observed in all cases. The reasons for this poor selectivity are discussed in terms of the interaction between the C2-O2 and C3-O3 bonds in the glucosyl and mannosyl donors and of the influence of this interaction on the ease of formation of the intermediate glycosyl oxacarbenium ions.     

4,6-O-benzylidene-directed beta-mannopyranosylation and alpha-glucopyranosylation: the 2-deoxy-2-fluoro and 3-deoxy-3-fluoro series of donors and the importance of the O2-C2-C3-O3 interaction

A series of 4,6-O-benzylidene-protected 2-O-benzyl-3-deoxy-3-fluoro- and 3-O-benzyl-2-deoxy-2-fluorogluco- and mannopyranosyl thioglycosides were synthesized and their coupling reactions with a series of alcohols, on preactivation with 1-benzenesulfinylpiperidine and trifluoromethanesulfonic anhydride, investigated. In all cases, the selectivities were lower than those observed with the corresponding simple 4,6-O-benzylidene 2,3-di-O-benzylgluco- and mannopyranosyl thioglycosides. This leads to the conclusion that the high beta-selectivity observed with 4,6-O-benzylidene 2,3-di-O-benzylmannopyranosyl donors under the same conditions is in large part derived from the compression of the O2-C2-C3-O3 torsion angle on going from the intermediate covalent glycosyl triflate to the oxacarbenium ion, as compared to the relaxation of this torsion angle in the gluco series.     

Electron-impact studies XCII–Negative ion-molecule reactions in anhydride systems. Perfluoroacetic anhydride with succinic,maleic and phthalic anhydrides. An ion cyclotron resonance study

The trifluoroacetate anion undergoes reaction with succinic, maleic and phthalic anhydrides to yield 1 : 1 adducts. The molecular anions of maleic and phthalic anhydride also undergo reaction with perfluoroacetic anhydride to produce [CF₃CO₂]^?· Maleic anhydride parent ions produce [M + CF₃CO·]^? ions when allowed to react with perfluoroacetic anhydride.     

Synergistic Pd/Cu catalysis enabled cross-coupling of glycosyl stannanes with sulfonium salts to access C-aryl/alkenyl glycals

A highly efficient coupling of glycosyl stannanes and sulfonium salts enabled by synergistic Pd/Cu catalysis is disclosed, facilitating the construction of C-aryl/alkenyl glycals under mild conditions in high yields. The protocol tolerates a wide scope of functional groups including ketone, cyano, ester, amide, nitro, halide. The one-pot formal CH glycosylation starting from arene is demonstrated with a reaction sequence of dibenzothiophenylation/Stille coupling. Besides, a gram-scale reaction is performed successfully, showing the high applicability of this protocol.