O,O-dimethylthiophosphonosulfenyl bromide-silver triflate: a new powerful promoter system for the preactivation of thioglycosides

O,O-Dimethylthiophosphonosulfenyl bromide (DMTPSB) in combination with silver triflate provides a powerful thiophilic promoter system. Both "armed" and "disarmed" thioglycoside glycosyl donors can be activated to form glycosidic linkages efficiently by the pre-activation protocol. The usefulness of this new promoter is illustrated by a successful iterative one-pot oligosaccharide assembly.     

Versatile synthesis and mechanism of activation of S-benzoxazolyl glycosides

As a part of a program for developing new efficient procedures for stereoselective glycosylation, a range of S-benzoxazolyl (SBox) glycosides have been synthesized. The mechanistic aspects of the SBox moiety activation for glycosylation via a variety of conceptually different pathways in the presence of thiophilic, electrophilic, or metal-based promoters have been investigated.     

Practical synthesis of latent disarmed S-2-(2-propylthio)benzyl glycosides for interrupted Pummerer reaction mediated glycosylation

Practical synthetic methods to latent disarmed S-2-(2-propylthio)benzyl (SPTB) glycosides for interrupted Pummerer reaction mediated glycosylation have been discovered. Among them, both coupling reaction of PTB-Cl with glycosyl thiols and BF₃·OEt₂ promoted reaction of peracylated glycosides with PTB-SH produced peracylated SPTB glycosides in large scales and with high efficiency.     

Dehydrative Glycosylation Enabled by a Comproportionation Reaction of 2‐Aryl‐1,3‐dithiane 1‐Oxide†

Summaryof main observation and conclusion A new dehydrativeglycosylation reaction has been established by capitalizing on the compropor-tionation reaction of 2-aryl-1,3-dithiane 1-oxides promoted by triflic anhydride(Tf2O).By wedding the high potency of thiophilic promoter system with the step efficiency of dehydrative glycosylation,this reagentunderwent facile intermolecular oxothio acetalization with C1-hemiacetal donor to install a temporary leaving group,rendering a transient electrophilic center at the remote site to the anomeric position.The sulfenyltriflate tethered at the ter-minus concomitantly activated the sulfide intramolecularly to afford the oxocarbenium ion,thereby facilitating the title glycosylation.Aside from accom-modating broad range functional groups and inactive hemiacetal substrates,the present activation protocol also proved expedient for 1,3-diol protection.Most importantly,this method further provided a fresh perspective for the application of sulfur chemistry to carbohydrate chemistry.     

Directing/protecting groups mediate highly regioselective glycosylation of monoprotected acceptors

A directing/protecting group designed for regioselective functionalization of partially-protected glucopyrannosides has been successfully used to prepare disaccharides in high yields. Most importantly, it has been demonstrated that highly regioselective and stereoselective glycosylation can be achieved when disarmed donors are employed. This study demonstrates the ability of directing/protecting group to induce regioselective glycosylation of carbohydrates and opens the field to the design of other DPGs for other monosaccharides.     

Regio- and Stereoselective Synthesis of Thioglycosides from 4,5-Diphenyl- and 3,4,5-Triphenylimidazole-2-thione

Six new thioglycosides incorporating the 4,5-diphenyl- and 3,4,5-triphenylimidazole moiety have been successfully synthesized under both conventional and microwave conditions by reaction of the corresponding thiones with aceto-bromosugars in presence of triethylamine as base. Attempted preparation of the bis(glycosyl) derivatives from 4,5-diphenylimidazole-2-thione in the presence of different bases was unsuccessful. Evaluation of the glycosylthioimidazoles as disarmed donors has been investigated using different promoters; NBS/TMSOTf has been found to be an effective promoter for the activation of the anomeric center towards glycosylation reaction.     

Convergent synthesis of a pentasaccharide repeating unit corresponding to the cell wall O-antigen of Salmonella enterica O44

A convergent synthetic strategy has been developed for the synthesis of a pentasaccharide fragment corresponding to the O-antigen of Salmonella enterica O44 strain. An intermediate tetrasaccharide derivative was prepared by a [2+2] block glycosylation of two disaccharide derivatives. The p-methoxybenzyl (PMB) group has been used as the in situ temporary protecting group minimizing the number of functional group manipulation steps. The application of the armed–disarmed glycosylation concept reduced the number of steps in the synthetic strategy. The glycosylation steps were highly stereoselective and high yielding.     

Amberlyst 15 as a mild and effective activator for the glycosylation with disarmed glycosyl trichloroacetimidate donors

Amberlyst 15 acidic resin has been shown to be a mild and effective activator for the glycosylation with commonly used disarmed glycosyl trichloroacetimidate donors. Glucosylation, galactosylation, rhamnosylation, and lactosylation of a panel of representative alcohol and thiol acceptors promoted by Amberlyst 15 allowed for the formation of structurally diverse O- or S-linked oligosaccharides and glycosylated amino acids in moderate to excellent yields.     

Solid-Phase Supported Synthesis of the Branched Pentasaccharide Moiety That Occurs in Most Complex Type N-Glycan Chains

Repetitive glycosylation on a sulfanylalkyl-functionalized Merrifield resin leads to the branched, complex pentasaccharide 1 in 20% overall yield in ten steps when appropriately protected O-glycosyl trichloroacetimidates are used as glycosyl donors. A decisive factor here was the tuning of the reaction conditions for the solid-phase glycosylation and the conditions for selective removal of the protecting groups and for cleavage of the samples from the resin for characterization. The subsequent cleavage of the product was achieved with a thiophilic reagent that does not attack the O-glycosidic linkages.     

Straightforward sequential and one-pot synthesis of a pentasaccharide repeating unit corresponding to the cell wall O-antigen of Shigella boydii type 18

Synthesis of a pentasaccharide repeating unit corresponding to the cell of wall O-antigen Shigella boydii type 18 has been achieved by sequential as well as iterative glycosylations in one-pot. Use of p-methoxybenzyl group (PMB) as an in situ removable protecting group allowed obtaining the desired pentasaccharide derivative in a generalized glycosylation condition and in one-pot condition. Synthesis of a beta-L-rhamnosidic linkage present in the molecule has been successfully achieved using l-rhamnosyl thioglycoside donor having a picoloyl group at remote C-3 position influencing beta selectivity in the glycosylation. A combination of N-iodosuccinimide (NIS) and perchloric acid supported over silica (HClO₄–SiO₂) has been used as thiophilic glycosylation promoter in all glycosylation reactions. TEMPO mediated selective oxidation of the primary hydroxyl group has been carried out at the late stage of the synthetic strategy.     

A Catalytic and Stereoselective Glycosylation with β‐Glycosyl Fluorides

A catalytic and stereoselective glycosylation of several glycosyl acceptors with β‐D ‐glycosyl fluoride was successfully performed in the presence of a catalytic amount of trityl tetrakis(pentafluorophenyl)borate (TrB(C₆F₅)₄) or trifluoromethanesulfonic acid (TfOH). When TrB(C₆F₅)₄ was used as a catalyst in the solvent pivalonitrile/(trifluoromethyl)benzene 1 : 5, the glycosylation proceeded smoothly to afford the glycosides in high yields with high β‐D ‐stereoselectivities (see Table 3). Further, the glycosylation by the armed‐disarmed strategy in the presence of this catalyst was established (see Table 4). Similarly, glycosylation catalyzed by the strong protic acid TfOH afforded the corresponding β‐D ‐glycosides in good‐to‐excellent yields on treating β‐D ‐ glycosyl fluorides having a 2‐O‐benzoyl group with various glycosyl acceptors including thioglycosides (see Tables 6 and 7).     

Highly Efficient Stereospecific Preparation of Tn and TF Building Blocks Using Thioglycosyl Donors and the Ph2SO/Tf2O Promotor System*

The activation of 2‐azido‐2‐deoxy Tn and TF thioglycosyl donors by the powerful thiophilic promoter system Ph₂SO/Tf₂O has been investigated. Glycosylation of an Fmoc‐protected threonine derivative gave 1,2‐cis glycosides in high yields and excellent stereoselectivities. The galactosylation of phenyl 2‐azido‐4,6‐O‐benzylidene‐2‐deoxy‐1‐thio‐β‐D‐galactopyranoside was achieved in high yield and without orthoester formation using a trichloroacetimidate donor carrying a 2‐O‐(2,5‐difluorobenzoyl) group. The anomeric thiophenyl group of the constructed TF disaccharide could directly be activated by the van Boom promotor for the glycosylation of a threonine derivative.     

Observations on the activation of methyl thioglycosides by iodine and its interhalogen compounds,

Treatment of ‘armed’ methyl thiogalactosides with iodine in the absence of an acceptor alcohol results in thioglycoside epimerisation, whereas there is no effect on the corresponding ‘disarmed’ methyl thioglycosides. In contrast, iodine–hexamethyldisilane (which generates iodotrimethylsilane in situ) brings about epimerisation of ‘disarmed’ thioglycosides, ultimately giving rise to the corresponding α-glycosyl iodides on extended exposure. Cross-over experiments show the former iodine-promoted epimerisation process to be intermolecular, whereas the latter iodine–hexamethyldisilane-promoted epimerisation is intramolecular. Treatment of the same methyl thiogalactosides with iodine monobromide gives rise to the thermodynamically favoured α-glycosyl bromides, whereas reaction with iodine monochloride initially gives the kinetic β-glycosyl chlorides, which slowly epimerise to the thermodynamic α-linked products. Differences in the outcome of thioglycoside activation by I–I, I–Br and I–Cl suggest there may be scope for influencing the stereochemical course of thioglycoside-based glycosylation reactions through careful choice of promoter.     

Stereoselective tris-glycosylation to introduce beta-(1-->3)-branches into gentiotetraose for the concise synthesis of phytoalexin-elicitor heptaglucoside

Dodecyl thioglycosides (3, 4, 5) were prepared by conventional transformation of d-glucose and used as new glycosyl donors for a short-step synthesis of phytoalexin elicitor heptaglucoside. A gentio-tetraoside derivative (6) having three hydroxyl groups was synthesized by NIS-TfOH promoted glycosylate in more than 90% yield followed by selective removal of temporary protective groups. Undesired formation of alpha-glycosides at the introduction of beta-(1-->3)-branches into gentio-oligosaccharides was found to be suppressed by use of a thiophilic reagent system, BSP (1-benzenesulfinyl piperidine)-Tf2O, giving the heptaglucoside in only four glycosylation steps.     

Purification of the 90 kDa heat shock protein (hsp90) and simultaneous purification of hsp70/hsc70, hsp90 and hsp96 from mammalian tissues and cells using thiophilic interaction chromatography

Heat shock proteins (HSPs) hsp70/hsc70, hsp90 and hsp96 were separated from mammalian cells and tissues on a gel obtained by the reaction of β‐mercaptoethanol with divinyl sulfone‐activated Sepharose CL‐6B (thiophilic gel or T‐gel). Hsp90 revealed a much higher affinity towards the T‐gel than the other HSPs. One‐step thiophilic interaction chromatography of proteins resulted in a more than 80% purity and 85% yield of hsp90. Based on this observation, a simple and efficient method for the purification of hsp90 and a procedure for the simultaneous purification of several HSPs (hsp70/hsc70, hsp90 and hsp96) using thiophilic interaction chromatography was developed. All the HSPs were recovered with a high yield and purity (90–99%). The results indicated that the thiophilic gel is a highly efficient affinity matrix for the purification of hsp90 and can be used in the protocols of purification of different HSPs from cells and tissues of various animal species. Copyright © 2009 John Wiley & Sons, Ltd.     

The effective and specific isolation of antibodies from human serum by using thiophilic paramagnetic polymer beads

A rapid and effective method to specifically isolate immunoglobulin G (IgG) from human serum by thiophilic paramagnetic polymer beads was developed. The thiophilic paramagnetic beads were synthesized with vinyl acetate and divinylbenzene by microsuspension polymerization in the presence of magnetite nanoparticles. Divinylsulfone and 2-mercapto-benzothiazole were subsequently used to modify the surface of these beads, resulting in thiophilic particles that exhibited a high specificity to the antibodies in serum at low salt concentration. The adsorbed IgG was eluted by 0.8 M KCl and 72% of the IgG in the serum was recovered. The purity of the isolated IgG reached 98.4% and the bioactivity was fully maintained (>99%). The high efficiency, mild conditions and simplicity make this technology suitable for the economic purification of antibodies in a large scale.     

Highly efficient synthesis of 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides through a sulfur-mediated reductive 2′,3′-trans-elimination. From iodomethylcyclopropanes to thiirane analogs

Taking into account the thiophilic properties of iodine, a very simple methodology to achieve 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides in high yield was performed, using mild, and inexpensive conditions, by means of the treatment of 2′-deoxy-3′,5′-dibenzoyl-2′-iodo-β-nucleoside derivatives with NaHS. The process has shown to be highly dependent of the relative geometry between the iodine atom and the adjacent leaving group. In this way, different essays carried out with pyranose derivatives have concluded in no reaction when the vicinal groups to eliminate do not adopt a trans-diaxial disposition. In addition, the treatment of 2-iodomethyl-cyclopropane-1,1-dicarboxylic acid diethyl ester under the same conditions softly and readily leads to the obtention of a mixture of the expected 2-allyl-malonic acid diethyl ester (as the minor product) and the thiirane derivative 2-thiiranylmethyl-malonic acid diethyl ester (as the major product). In this case, the responsible of the reaction progress are the nucleophilic properties of the sulfur atom rather than the thiophilic character of the iodine atom.     

Chromatographic and fluorometric study of interactions between thiophilic and hydrophobic ligands and tryptophan peptide homologues

The interactions of tryptophan and its peptide homologues with thiophilic ligands were studied in terms of their chromatographic retention and steady-state fluorescence under various conditions, and compared with non-polar structures typically regarded as pure hydrophobic ligands. The experimental results show that both non-polar and polar interactions are involved in what has been termed "thiophilic adsorption chromatography".     

Chelate von β-Dicarbonylverbindungen und ihren Derivaten. XV. Komplexchemische Reaktivität von β-Mercaptovinylaldehyden

The reactivity of α-phenyl-β-mercaptocinnamaldehyde and α-(2-pyridyl)-β-mercaptocinnamaldehyde towards thiophilic metals was studied and some complexes of nickel, cobalt, copper, palladium, zinc, lead and mercury with these ligands were prepared. The chemical bonding in the complexes was examined by IR spectroscopy. The reaction of the Bis(α-phenyl-β-mercaptocinnamaldehydato)-nickel with amines gave the corresponding aldimine chelates, by the action of hydrogen sulfide the nickel chelate of α-phenyl-β-mercaptocinnamthioaldehyde was formed.     

Salt promoted adsorption chromatography of malted barley amylases

Summary A sequence for the fractionation of the amylasic components from a malted barley extract is proposed using two salt-promoted, adsorption processes: thiophilic interaction chromatography (TIC) and hydrophobic interaction chromatography (HIC).Two fractions containing -amylase activity were recovered during the thiophilic chromatography; the first was resolved in to -amylase I and -amylase I by HIC on a phenyl-sepharose column; an enrichment factor of 32 was achieved for -amylase I. The other amylasic component eluted from the thiophilic gel was characterized as -amylase II. Although the adsorption of malt amylases on phenylsepharose and the thiophilic adsorbent is salt promoted, the interactions involved in each case are clearly distinguished by the different behaviour and disparate salt effects.