Acetylated methyl glucopyranuronate trichloroacetimidate as a glycosyl donor for efficient synthesis of disaccharides

Allyl (methyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosyl uronate)-(1-->3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (4) and benzyl (methyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosyl uronate)-(1-->3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (5) have been efficiently synthesized by coupling allyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (2) or benzyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (3) with methyl (2,3,4-tri-O-acetyl-1-O-trichloroacetimidoyl)-alpha-D-glucopyranuronate (1), respectively, using trimethylsilyl triflate as promoter.     

Convenient solid-phase synthesis of oligopeptides using pentacoordinated phosphoranes with amino acid residue as building blocks

The reactive intermediates of pentacoordinated phosphoranes with amino acids (P(5)-AA) as building blocks, which were obtained by the reaction of O-phenylene phosphorochloridate with N,O-bis(trimethylsilyl)amino acids, were linked to a solid-phase support containing a hydroxymethyl polystyrene functional group. The first amino acid residue was coupled to the solid-phase support after washing the resin with organic solvent. Repeating the procedure led to oligopeptides linked on the resin. A series of free oligopeptides including tetra-Gly, di-Val, tri-Val, di-Leu, di-Phe, and Phe-Leu were obtained after cleavage from solid-phase support. The structure of these oligopeptides were determined by IR, (1)H NMR, FAB-MS, and HPLC.     

Natural phosphoglycans containing glycosyl phosphate units: structural diversity and chemical synthesis

An anomeric phosphodiester linkage formed by a glycosyl phosphate unit and a hydroxyl group of another monosaccharide is found in many glycopolymers of the outer membrane in bacteria (e.g., capsular polysaccharides and lipopolysaccharides), yeasts and protozoa. The polymers (phosphoglycans) composed of glycosyl phosphate (or oligoglycosyl phosphate) repeating units could be chemically classified as poly(glycosyl phosphates). Their importance as immunologically active components of the cell wall and/or capsule of numerous microorganisms upholds the need to develop routes for the chemical preparation of these biopolymers. In this paper, we (1) present a review of the primary structures (known to date) of natural phosphoglycans from various sources, which contain glycosyl phosphate units, and (2) discuss different approaches and recent achievements in the synthesis of glycosyl phosphosaccharides and poly(glycosyl phosphates).     

Modified PNAs: a simple method for the synthesis of monomeric building blocks

The synthesis of PNA-monomers with variations in the substitution pattern using the Ugi-Reaction is described. The one-pot procedure leads to new totally protected PNA-monomers which can be selectively cleaved to N-protected monomeric building blocks for PNA synthesis.     

Chemoselectively addressable HCan building blocks in peptide synthesis: L-homocanaline derivatives

(S-2-amino-5-(aminooxy)pentanoic acid (L -homocanaline, HCan), a structural analogue of lysine, contains a reactive alkyloxyamine side chain and is therefore considered to react chemoselectively with carbonyl compounds by forming a kinetically stable oxime bond. The chemical synthesis of L -homocanaline starting from protected glutamic acid derivatives is described. Two orthogonally protected homocanaline derivatives were synthesized and their use in standard SPPS procedures was exemplified for the synthesis of a chemoselectively addressable cyclic peptide for use in TASP design. Moreover, the wide range of applications of this unique building block was demonstrated for the chemoselective ligation of an unprotected disaccharide to a HCan containing model peptide resulting in a chimeric glycopeptide structure. © 1998 European Peptide Society and John Wiley & Sons, Ltd.     

Carbohydrate-modulated DNA photocleavage: design, synthesis, and evaluation of novel glycosyl anthraquinones

Novel and artificial anthraquinone-carbohydrate hybrids were designed and synthesized, and found to effectively cleave DNA under irradiation with a long wavelength UV light and also exhibit cytotoxicity against HeLa S3 cells.     

Different strategies for the synthesis of 2'-O-aminoethyl adenosine building blocks

The chemical modification of the 2'-O-position of nucleosides proved to be of great importance for the RNA stability. Greater stability of RNA duplexes allows a longer half life in the cell and, therefore, a better effect of RNA Interference. Here we investigated the synthesis of 2'-O-aminoethyl adenosine as a cationic modified building block.     

Synthesis of building blocks for solid-phase introduction of diethylenetriaminepentaacetic acid (DTPA) to oligonucleotides and oligopeptides

Synthesis of building blocks that allow site-specific incorporation of diethylenetriaminepentaacetic acid (DTPA) to oligonucleotides and oligopeptides using phosphoramidite and Fmoc chemistries, respectively, is described.     

Significant rate accelerated synthesis of glycosyl azides and glycosyl 1,2,3-triazole conjugates

An efficient and significantly rapid access of a series of glycosyl azides and glycosyl 1,2,3-triazole conjugates is reported using modified one-pot reaction conditions. In both cases yields were excellent and single diastereomers were obtained. Figure Rapid preparation of 4-substituted glycosyl 1,2,3-triazole conjugates from glycosyl bromides. CDRI communication no. 7340.     

Thiophenolate clusters as potential nanosized building blocks for zinc-based nanocomposite materials: synthesis and characterization

The synthesis, the spectroscopic and structural characterization of different thiophenolate-capped zinc clusters are reported and described. In particular, different reactions of 4-chlorobenzenethiol with zinc salts yield the clusters [Me₄N][Et₃NH][Zn₄(μ-S-C₆H₄-Cl)₆(S-C₆H₄-Cl)₄] (2a), [Et₃NH]₂[Zn₄(μ-S-C₆H₄-Cl)₆(S-C₆H₄-Cl)₄] (2b), and [Me₄N]₂[Zn₄(μ-S-C₆H₄-Cl)₆(S-C₆H₄-Cl)₄] (2c), and also the thiophenolate derivative [Et₃NH]₂[Zn₄(μ-S-C₆H₅)₆(S-C₆H₅)₄] (1b) was obtained.The nanosized thiophenolate-capped clusters were investigated by ¹H and ¹³C NMR, elemental analysis, and electrospray ionization (ESI) mass spectrometry. NMR experiments provided insights into the dynamic behaviour of the clusters. The thermal decomposition patterns of 2c were analyzed in air as well as in nitrogen, indicating the formation of zinc oxide and metallic zinc, respectively. The X-ray structure of 2a revealed that the cluster core consists of an adamantane-like framework analogous to those realized in many other M₄(SR)₁₀ metal complexes.     

PDZ domains: the building blocks regulating tumorigenesis

Over 250 PDZ (PSD95/Dlg/ZO-1) domain-containing proteins have been described in the human proteome. As many of these possess multiple PDZ domains, the potential combinations of associations with proteins that possess PBMs (PDZ-binding motifs) are vast. However, PDZ domain recognition is a highly specific process, and much less promiscuous than originally thought. Furthermore, a large number of PDZ domain-containing proteins have been linked directly to the control of processes whose loss, or inappropriate activation, contribute to the development of human malignancies. These regulate processes as diverse as cytoskeletal organization, cell polarity, cell proliferation and many signal transduction pathways. In the present review, we discuss how PBM-PDZ recognition and imbalances therein can perturb cellular homoeostasis and ultimately contribute to malignant progression.     

Design,synthesis and biological evaluation of azithromycin glycosyl derivatives as potential antibacterial agents

A series of 11,12-cyclic carbonate azithromycin-4″-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated as antibacterial agents to search for target compounds with excellent activity. The results of preliminary antibacterial tests against eight strains in vitro revealed that all of the title compounds exhibited improved activities with broad spectrum compared with the parent compound. The glycosylated side chains may be the pharmacophores responsible for the improved activity.     

Investigation of the automated solid-phase synthesis of a 38mer peptide with difficult sequence pattern under different synthesis strategies

Difficult peptides are a constant challenge in solid-phase peptide synthesis. In particular, hydroxyl amino acids such as serine can cause severe breakdowns in coupling yields even several amino acids after the insertion of the critical amino acid. This paper investigates several methods of improving synthesis yields of difficult peptides including the use of different resins, activators and the incorporation of a structure-breaking pseudoproline dipeptide building block both alone and in combination with each other.     

Toward a catalytic site in DNA: polyaza crown ether as non-nucleosidic building blocks in DNA conjugates

A number of functionalized polyaza crown ether building blocks have been incorporated into DNA-conjugates as catalytic Cu(2+) binding sites. The effect of the DNA-conjugate catalyst on the stereochemical outcome of a Cu(2+)-catalyzed Diels-Alder reaction will be presented.     

Base-pairing systems related to TNA containing phosphoramidate linkages: synthesis of building blocks and pairing properties

As part of a project that aims at screening TNA-related oligonucleotide systems in which threose backbone units may have some or all of their oxygen functions replaced by nitrogen, two TNA analogs containing (2'NH)- and (3'NH)-phosphoramidate groups, respectively, in place of phosphodiester groups were synthesized. They show base-pairing properties that are very similar to those of TNA itself. We also synthesized 2',3'-diamino analogs of alpha-L-threofuranosyl mononucleosides, yet attempts to convert them to TNA analogs containing phosphodiamidate linker groups were not successful. Such 2',3'-diamino derivatives of threofuranosyl nucleosides may be of interest, however, as building blocks of TNA analogs that contain non-phosphorous linker groups.     

Enzymatic preparation of heparin disaccharides as building blocks in glycosaminoglycan synthesis.

Pharmaceutical heparin and heparan sulfate, isolated from a side-stream of a commercial heparin manufacturing process, have been enzymatically depolymerzed with heparin lyases obtained from Flavobacterium heparinun. Heparin afforded a trisulfated disaccharide product that was recovered from the reaction mixture using gel permeation chromatography. Heparan sulfate afforded unsulfated disaccharide that was conveniently recovered from the product mixture by ion exchange chromatography. Both disaccharides were obtained in gram amounts at 90% or higher purity. Both enzymatically prepared disaccharides were chemically protected to prepare building blocks required for the future chemical synthesis of therapeutically valuable heparin oligosaccharides.     

Alpha-hydroxybenzylphosphonate modified oligonucleotides: synthesis, properties, and a novel route via monomer building blocks

In general, alpha-hydroxybenzylphosphonate modified 2'-deoxyadenosine-thymidine dimer building blocks 1, 2 are utilized for the incorporation into alpha-hydroxybenzylphosphonate pro-oligonucleotides. For a universal application of our pro-oligonucleotide concept on biologically relevant oligonucleotides a route for the synthesis of modified monomer building blocks 3 was developed and is presented herein.     

New Fmoc pseudoisocytosine monomer for the synthesis of a bis-PNA molecule by automated solid-phase Fmoc chemistry

The synthesis of N-[2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-(2-N-(benzyloxycarbonyl)isocytosin-5-ylacetyl)glycine monomer and its incorporation into a PNA molecule via automated Fmoc solid-phase chemistry is described.     

Glucosylenamines as glycosyl acceptors: synthesis of gentiobiosylenamines.

The preparation of 2,3,4-tri-O-benzyl- (3), 2,3,4-tri-O-acetyl- (4), and 2,3,4-tri-O-benzoyl-N-(2,2-diethoxycarbonylvinyl)-6-O-trityl-beta- D-glucopyranosylamine (5) is described. The reaction of 3-5 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide yields 2,3,4-tri-O-benzyl- (9), 2,3,4-tri-O-acetyl- (10), and 2,3,4-tri-O-benzoyl-N-(2,2-diethoxycarbonylvinyl)-6-O-(2,3,4,6-tet ra-O- acetyl-beta-D-glucopyranosyl)-beta-D-glucopyranosylamine (11), respectively. 2,3,4-Tri-O-benzyl- (6), 2,3,4-tri-O-acetyl- (7), and 2,3,4-tri-O- benzoyl-N-(2,2-diethoxycarbonylvinyl)-beta-D-glucopyranosylamine (8) are also described.