Arabinofuranosides from mycobacteria: synthesis of a highly branched hexasaccharide and related fragments containing beta-arabinofuranosyl residues

The synthesis of 11 oligosaccharides (4-14) containing beta-arabinofuranosyl residues is reported. The glycans are all fragments of two polysaccharides, arabinogalactan and lipoarabinomannan, which are found in the cell wall complex of mycobacteria. In the preparation of the targets, the key step was a low-temperature glycosylation reaction that installed the beta-arabinofuranosyl residues with good to excellent stereocontrol.     

The first total synthesis of a highly branched arabinofuranosyl hexasaccharide found at the nonreducing termini of mycobacterial arabinogalactan and lipoarabinomannan

[reaction--see text] The first total synthesis of the arabinofuranosyl hexasaccharide present at the nonreducing termini of mycobacterial arabinogalactan and lipoarabinomannan is reported. The oligosaccharide was prepared as its methyl glycoside via a route that is both highly efficient and convergent. Addition of two beta-D-arabinofuranosyl residues simultaneously in high yield and with excellent stereocontrol was the key step of the synthesis.     

Synthesis of N-acetyllactosamine based branched hexasaccharide

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Solution-phase hexasaccharide synthesis using glucosyl iodides

[reaction: see text] Oligosaccharides composed of 1,6-glucosyl residues have been prepared from glucosyl iodides. The reactions are highly stereoselective, giving the alpha-glycosides as the only isolated products in yields ranging from 84% to 94%. Oligomer synthesis can take place in an iterative 1 + 1 + 1 fashion or in a convergent manner where dimer iodides serve as donors for higher order acceptors.     

Solid-phase synthesis of photoaffinity probes: highly efficient incorporation of biotin-tag and cross-linking groups

A benzophenone cross-linking group and a biotin-tag hybrid, resin 1a, attached to our novel resin 2 was readily converted to the photoaffnity probe 20 by condensation with the ligand carboxylic acid 19 and cleavage from the resin without purification.     

Solid-phase synthesis of tetrasubstituted 2-imino-1,3-thiazolines using a functionalizing cleavage strategy

A novel solid-phase synthesis of tetrasubstituted 2-imino-1,3-thiazolines using a functionalizing cleavage strategy is described. The synthetic route utilized the ambident reactivity of a dithiocarbamate functionality to synthesize the key resin-bound electrophilic thiazolium intermediate. The desired products were efficiently obtained in high purity by the reaction of various amines with the thiazolium salt.     

Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin.

A trialkoxy-diphenyl-methylester and amide linkage for solid-phase peptide synthesis with Fmoc strategy is described. Protected peptide esters can be smoothly cleaved with weak acid, resulting in fragments with intact side-chain protection. Mild acidic cleavage of the corresponding peptide amide resins yields peptide amides.     

Solid-phase synthesis of NMe-IB-01212, a highly N-methylated cyclic peptide

N-Methylation of peptides is an important synthetic tool in peptide-based medicinal chemistry. Herein, an optimized strategy for solid-phase synthesis of small but highly N-methylated cyclic peptides is described. The proposed route addresses several problems associated with the synthesis of peptides containing several sequential N-methyl-amino acids, such as in situ N-methylation, difficulty of acylation, epimerization, diketopiperazine formation, and stability at the NMe sites under trifluoroacetic acid exposure. The resulting NMe-IB-01212 exhibits micromolar activity and considerable stability.     

Solid-phase synthesis of oligourea peptidomimetics employing the Fmoc protection strategy.

A solid-phase-Fmoc-based-synthesis strategy is described for oligourea peptidomimetics as well as a convenient general synthesis approach for the preparation of the required building blocks 5a-j and 5k. These are suitable for use in peptide or robot synthesizers, which is illustrated by the synthesis of oligourea peptidomimetics of part of Leu-enkephalin (10) and a neurotensin derivative (17).     

Solid-phase synthesis of a library of C-terminal agmatine dipeptides using a backbone amide linker (BAL) strategy

In this Letter, we report a novel solid-phase strategy using a backbone amide linker (BAL) attached to a polystyrene support for the synthesis of C-terminal agmatine dipeptides. Our method eliminates the need to purify intermediates by column chromatography and enables us to build rapidly an 18-member library of C-terminal agmatine dipeptides which are subsequently screened for inhibitory activity against a viral enzyme.     

Solid-phase synthesis of asymmetrically branched sequence-defined poly/oligo(amidoamines)

We present for the first time the synthesis of asymmetrically branched sequence-defined poly/oligo(amidoamines) (PAAs) using solid-phase synthesis with the capability of introducing diversity at the side chains. We introduce two new versatile (diethylenetriamine) building blocks for solid-phase synthesis bearing Fmoc/Boc and Fmoc/Alloc protecting groups expanding recently used Fmoc/Boc protecting group strategy for linear PAAs to an Fmoc/Alloc/Boc strategy. This allows for orthogonal on-resin cleavage of Fmoc and Alloc protecting groups during solid-phase synthesis of PAAs with backbones differing in chain length and sequence. With these structures we then demonstrate the potential for generating asymmetrical branching by automated multiple on-resin cleavage of Alloc protecting groups as well as the introduction of side chains varying in length and number. Such systems have high potential as nonviral vectors for gene delivery and will allow for more detailed studies on the correlation between the degree of branching of PAAs and their resulting biological properties.     

Facile synthesis of polystyrene bearing highly branched perfluorinated groups

A novel styrene monomer with a highly branched perfluoroalkenyl group was readily prepared in good yield from hexafluoropropene trimer and hydroxystyrene. The fluorinated monomer radically polymerized yielded a white powdery polymer which was soluble in fluorinated solvents and had good water repellency. The polymer had a unique high glass transition temperature despite the introduction of perfluorinated groups. The monomer was copolymerized with styrene, and their monomer reactivity ratios were determined.     

Solid-phase synthesis of N-alkyl-N-(beta-keto)amides and 1,2,4,5-tetrasubstituted imidazoles using a traceless cleavage strategy

[reaction: see text] The solid-phase synthesis of N-alkyl-beta-keto)amides and 1,2,4,5-tetrasubstituted imidazoles was demonstrated using a traceless cleavage strategy based on benzylic acylammonium chloride reactivity. The approach enables the assembly of diverse compounds in a minimal number of steps in moderate to excellent yield (23-88%) and high purity (64-100%).     

A novel and highly efficient synthetic route to unsymmetrical organoselenides using cesium bases

A new and convenient one-pot method for the preparation of unsymmetrical selenides has been developed. In the presence of cesium hydroxide, molecular sieves, and DMF, benzeneselenol undergoes direct alkylation with various alkyl halides for the synthesis of alkyl phenyl selenides in moderate to excellent yields. Another method to prepare unsymmetrical organoselenides was also completed by coupling terminal alkynes with benzeneselenyl bromide. As an application, the synthesis of a selenopeptide was also accomplished. Furthermore, this methodology was extended to the synthesis of an organoselenide on solid support.     

Ultrasound-promoted green synthesis of 1,4-dihydropyridines using fuctionalized MWCNTs as a highly efficient heterogeneous catalyst

A new method for multi-component synthesis of 1,4-dihydropyridine derivatives (1,4-DHPs) in the presence of meglumine supported on multiwalled carbon nanotubes (MWCNTs@meglumine) as a new heterogeneous, highly efficient and reusable catalyst was investigated. The reaction was performed under ultrasonic irradiation in EtOH at room temperature. A new, highly efficient heterogeneous catalyst, short reaction times, high to excellent yield of products, and safe and clean conditions are the advantages of the presented method.     

Solid-phase synthesis of complex oligosaccharides using a novel capping reagent

Solid-phase-supported oligosaccharide synthesis of a core N-glycan tetrasaccharide and of a trisaccharide containing the Galili antigen is reported. The synthesis is based on a hydroxymethylbenzyl benzoate spacer-linker system attached to the Merrifield resin, O-Fmoc-protected O-glycosyl trichloroacetimidates as glycosyl donors, and benzoyl isocyanate as a capping reagent for low-reactivity hydroxy groups. In this way, the target molecules could be efficiently obtained with little byproduct formation, and hence final purification was convenient.     

Solid-phase synthesis of indolecarboxylates using palladium-catalyzed reactions

Polymer-supported, palladium-catalyzed cyclization reactions effectively synthesized indolecarboxylates. Palladium-catalyzed carbon-carbon bond-forming reactions of immobilized enaminoesters followed by transesterification yielded indole 2- or 3-carboxylates with various functional groups on the benzene ring. Indolecarboxylates were efficiently cyclized via an intramolecular palladium-catalyzed amination reaction of immobilized N-substituted dehydrohalophenylalanines, and immobilized N-acetyl-dehydroalanines were efficiently converted into indolecarboxylates via tandem Heck-amination reactions.