Microwave-assisted acylation of amines, alcohols, and phenols by the use of solid-supported reagents (SSRs)

A microwave-assisted synthesis of solid-supported reagents for the acylation of amines has been developed, and the same methodology has been successfully applied to the preparation of acylating agents anchored on different solid supports. Similarly, alcohols, phenols, and thiophenols have been easily acylated using these reagents under microwave irradiation.     

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.     

New and efficient synthesis of solid-supported organotin reagents and their use in organic synthesis

Novel resin-bound organotin reagents have been prepared, including for the first time resin-bound dimethyl tin reagents. Mild methodology has also been developed for the very efficient synthesis of resin-bound distannanes. The resin-bound tin chloride reagents have been used in a catalytic Stille coupling cycle and the resin-bound distannanes have been used in atom transfer cyclisations and proved to be much more effective than previously described resin-bound distannanes. As expected the use of resin-bound tin reagents facilitated their easy removal at the end of the reaction, and consequently residual tin levels in the organic products were low or negligible. The resin-bound distannanes could not, however, be successfully used for the palladium catalysed stannylation of a simple aryl iodide, which would have provided a useful approach to radiolabeling of aromatic substrates. The reasons for the failure in the stannylation process is unclear but crystal structure evidence indicates that there is a hypervalent interaction between the resin-bound tin atom and an adjacent ether oxygen which may effect the reactivity of the tin intermediates in the stannylation sequence.     

Stereoselective direct glycosylation with anomeric hydroxy sugars by activation with phthalic anhydride and trifluoromethanesulfonic anhydride involving glycosyl phthalate intermediates

An efficient direct one-pot glycosylation method with anomeric hydroxy sugars as glycosyl donors employing phthalic anhydride and triflic anhydride as activating agents has been developed. Thus, highly stereoselective beta-mannopyranosylations were achieved by the reaction of 2,3-di-O-benzyl-4,6-O-benzylidene-D-mannopyranose (2) with phthalic anhydride in the presence of DBU at room temperature followed by sequential addition of DTBMP and Tf2O and glycosyl acceptors to the reaction mixture at -78 degrees C in one-pot. Stereoselective alpha-glucopyranosylations with 2,3-di-O-benzyl-4,6-O-benzylidene-D-glucopyranose (25) and other glycosylations with glucopyranoses and mannopyranoses having tetra-O-benzyl- and tetra-O-benzoyl protecting groups were also possible by utilizing the present one-pot glycosylation protocol. The possible mechanism for the beta-mannosylation with 2 was proposed based on the NMR study, in which alpha-mannosyl phthalate 55alpha and alpha-mannosyl triflate 59 were detected as intermediates. The versatility and efficiency of the present glycosylation methodology, especially those of the beta-mannopyranosylation protocol, were readily demonstrated by the efficient synthesis of protected beta-(1-->4)-D-mannotriose 62 and beta-(1-->4)-D-mannotetraose 67 with perfect beta-stereoselectivity.     

A glycosylation reaction: Conversion of methyl glicosides to glycosyl chlorides by boron trichloride

Methyl glycosides react readily with boron trichloride in dichloromethane solutions at −78 °C to give the corresponding glycosyl chlorides for subsequent use in glycosylation reactions. This reaction is compatible with the presence of glycosyl linkages in the molecule, as well as benzyl and acetyl protecting groups.     

One-pot catalyst preparation: combined detemplating and Fe ion-exchange of BEA through Fenton's chemistry

BEA zeolite has been simultaneously detemplated and Fe-exchanged by treating the parent zeolite with a Fenton's-type reagent (Fe3+-H2O2) at low temperature. This one-pot process simplifies and speeds up considerably the preparation route. The catalyst shows excellent performance on N2O decomposition compared to conventionally prepared Fe-BEA.     

The use of solid-supported reagents for the multi-step synthesis of analytically pure alpha,beta-unsaturated compounds in miniaturized flow reactors

Micro reaction technology offers a safe, controllable and information rich technique suitable for the long-term production of pharmaceutical agents and fine chemicals. To date however, few of the syntheses performed using this technology have addressed the problems associated with product purification. With this in mind, we report herein the incorporation of multiple supported reagents into EOF-based miniaturized flow reactors for the two-step synthesis of analytically pure compounds. Using this approach, the successful synthesis of 20 alpha,beta-unsaturated compounds in excellent yields (>99.1%) and purities (>99.9%) has been achieved, illustrating significant improvements compared to traditional batch techniques.     

Halobenzoyl groups in glycosylation: effect on stereoselectivity and reactivity of glycosyl donors

Described herein is the synthesis and evaluation of a series of glycosyl donors equipped with halobenzoyl substituents at O(4) and O(6) to study their properties in glycosylations. Among possible effects that may include carbonyl participation or H-bond mediated aglycone delivery, our results indicate that halobenzoyls act via a different mode.     

Chemoselective high-throughput purification mediated by solid-supported reagents: its application to the first 6, 9-disubstituted purine library synthesis

A new application of solid-supported reagents was developed to separate the alkylated N7/N9 regioisomers derived from commercially available 2-amino-6-chloropurine. Simple filtration through an alumina/H+ pad or scavenging by AG/Dowex-50W-X8 resin provides diverse N9 regioisomers selectively in moderate yields with high purities (>90%). This purification method can be conveniently used in a high-throughput format and facilitates the synthesis of a purine library without laborious regioisomer separation and aqueous work-up. The first library synthesis of 6,9-disubstituted purines is reported using the combination of this novel separation method in conjunction with polymer-supported reagents.     

Fluorescent magnetic nanocrystals by sequential addition of reagents in a one-pot reaction: a simple preparation for multifunctional nanostructures

Core-shell nanostructures consisting of FePt magnetic nanoparticles as the core and semiconducting chalcogenides as the shell were synthesized by a series of reactions in a one-pot procedure. Adding Cd(acac)2 as the cadmium precursor to a reaction mixture containing FePt nanoparticles afforded FePt@CdO core-shell intermediates. The subsequent addition of chalcogens yielded FePt@CdX core-shell nanocrystals (where X was S or Se). The reverse sequence of addition, i.e., adding X before Cd, resulted in spongelike nanostructures because the chalcogens readily formed nanowires in the solution. Transmission electron microscopy, energy-dispersive X-ray spectrometry, selected area electron diffraction, fluorescence spectroscopy, and SQUID were used to characterize the nanostructures. These core-shell nanostructures displayed superparamagnetism at room temperature and exhibited fluorescence with quantum yields of 2.3-9.7%. The flexibility in the sequence of addition of reagents, combined with the compatibility of the lattices of the different materials, provides a powerful yet convenient strategy for generating sophisticated, multifunctional nanostructures.     

An operationally simple,fast and green synthesis of novel γ-hydroxyphosphonate and phosphine oxide derivatives

A green and versatile method for the preparation of γ-hydroxyphosphonate and phosphine oxide derivatives in 5?min, is accomplished through the reduction of γ-phosphonylketones with sodium borohydride supported on alumina, at room temperature, under solvent free conditions.     

Investigating bacterial N-linked glycosylation: synthesis and glycosyl acceptor activity of the undecaprenyl pyrophosphate-linked bacillosamine

The chemical synthesis and biological activity of undecaprenyl pyrophosphate bacillosamine (Und-PP-Bac), an obligatory intermediate in the asparagine-linked glycosylation pathway of Campylobacter jejuni, are reported. The key transformation involves the coupling of bacillosamine phosphate and undecaprenyl phosphate. The synthetic Und-PP-Bac can be used to investigate the activity of the enzyme PglA, which catalyzes the first glycosyl transfer in substrate biosynthesis for N-linked protein glycosylation in the pathogenic gram-negative bacterium. The availability of this synthetic substrate makes it possible to access polyprenyl-linked oligosaccharides, such as the GalNAc-alpha-1,3-bacillosamine-alpha-1-PP-Und intermediate, that will enable exploration of the remaining enzymes in the prokaryotic glycosylation pathway. Study of the bacterial glycosylation system will provide insight into the corresponding eukaryotic process, which is currently poorly understood.     

A new, efficient glycosylation method for oligosaccharide synthesis under neutral conditions: preparation and use of new DISAL donors

Efficient, stereoselective glycosylation methods are required for the synthesis of complex oligosaccharides as tools in glycobiology. All glycosylation methods, which have found wide acceptance, rely on Lewis acid activation of glycosyl donors prior to glycosylation. Here, we present a new and efficient method for glycosylation under neutral or mildly basic conditions. Glycosides of methyl 2-hydroxy-3,5-dinitrobenzoate (DISAL) and its para regioisomer, methyl 4-hydroxy-3,5-dinitrobenzoate, were prepared by nucleophilic aromatic substitution. In a first demonstration of their potential as glycosyl donors, stereospecific glycosylation of methanol was achieved. In the glycosylation of more hindered alcohols, the beta-donor proved more reactive, and alpha-glucosides were predominantly formed. Glycosylation of protected monosaccharides, with free 6-OH or 3-OH, proceeded smoothly in 1-methyl-2-pyrrolidinone (NMP) at 40-60 degrees C in the absence of Lewis acids and bases in good to excellent yields. Glycosylation of 3-OH gave the alpha-linked disaccharide only.     

One-pot preparation of phenylpropanoid esters co-catalyzed by boric acid and piperidine

Phenylpropanoid esters, especially those with hydroxyl and/or methoxy groups on the benzene ring, are important medicinal chemicals or intermediates. They are usually prepared by esterification of their corresponding substituted cinnamic acids with various alcohols. However, the esterification procedures often suffer from environmentally hazardous problems when sulfuric acid is used as a catalyst or suffer from unsatisfactory yields and expensive raw material when enzyme is applied as a catalyst. In this paper, a convenient one-pot process for preparing various phenylpropanoid esters from substituted benzaldehydes bearing hydroxyl and/or methoxyl groups has been developed. The alcohols react first with malonic acid catalyzed by boric acid to form monomalonate, then without separation, let the resultant mixture immediately react with the injected various substituted benzaldehydes in the presence of piperidine to afford the desired esters with moderate to good yields.     

A selective and operationally simple approach for removal of methoxy-, allyloxy-, and benzyloxycarbonyl groups from carbinols

LiI in refluxing pyridine can remove within a few hours methoxy-, allyloxy-, and benzyloxycarbonyl groups from saccharidic carbinols under conditions compatible with the maintenance of acyl groups. Addition of a stoichiometric excess of acetic acid to the reaction mixture minimizes or even suppresses intramolecular transesterifications. The procedure broadens the scope of some alkoxycarbonyl groups in organic synthesis.     

Novel solid-supported dimerization-heteroannulation of chalcones: simple and efficient synthesis of 2,4,6-triaryl-3-methylarylpyridines

2,4,6-Triaryl-3-methylarylpyridines were obtained, in 60-70% yield, by a novel one-pot solventless solid-supported dimerization-heteroannulation reaction of chalcones and compounds possessing terminal -CONH₂ functionality, at 125-135 °C, using immobilized Bi(III) nitrate and Zn(II) chloride as co-catalyst. Initially, chalcones were prepared, in nearly quantitative yield, by a modified aldol condensation, in neutral aqueous medium, in the presence of p-toluenesodium sulfonate.     

Complete functionalisation of small and large diameter bromopolystyrene beads; applications for solid-supported reagents, scavengers and diversity-oriented synthesis

Bromopolystyrene beads with diameters of up to 600 microm have been derivatized completely, via bromine-magnesium exchange and interception with electrophiles, to yield high quality solid-supported reagents, scavengers and solid supports for use in diversity-oriented synthesis.     

1-Fluoropyridinium triflates: versatile reagents for transformation of thioglycoside into O-glycoside, glycosyl azide and sulfoxide

1-Fluoropyridinium triflates are versatile reagents to transform thioglycoside into O-glycoside, glycosyl azide and sulfoxide. The electronic nature of the substituents on the pyridine ring can control their ability to activate thioglycosides.