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Oligonucleotides incorporating a central C‐nucleoside with either a rigid or flexible benzaldoxime base moiety have been synthesized, and the hybridization properties of their metallacyclic derivatives have been studied by UV melting experiments. In all cases, the metallated duplexes were less stable than their unmetallated counterparts, and the metallacyclic nucleobases did not show a clear preference for any of the canonical nucleobases as a base‐pairing partner. With palladated oligonucleotides, increased flexibility translated to less severe destabilization, whereas the opposite was true for the mercurated oligonucleotides; this reflects the greater difficulties in accommodating a rigid PdII‐mediated base pair than a rigid HgII‐mediated base pair within the base stack of a double helix., Take the strain: A flexible PdII‐mediated base pair of a benzaldoxime palladacycle disrupts oligonucleotide hybridization less than its rigid analogue, whereas the opposite is true for HgII‐mediated base pairs. With a base pair of an incompatible geometry, increased flexibility alleviates some of the strain; with a strain‐free base pair it merely leads to an increased entropic penalty of hybridization.

Owing to the environmental concern worldwide and also due to cost, time and labour issues, use of one-pot reactions [domino/cascade/tandem/multi-component (MC) or sequential] has gained much attention among the scientific and industrial communities for the generation of compound libraries having different scaffolds. Inclusion of sugars in such compounds is expected to increase the pharmacological efficacy because of the possibility of better interactions with the receptors of such unnatural glycoconjugates. In many of the one-pot transformations, the presence of a metal salt/complex can improve the reaction/change the course of reaction with remarkable increase in chemo-/regio-/stereo-selectivity. On the other hand because of the importance of natural polymeric glycoconjugates in life processes, the development and efficient synthesis of related oligosaccharides, particularly utilising one-pot MC-glycosylation techniques are necessary. The present review is an endeavour to discuss one-pot transformations involving carbohydrates catalysed by a metal salt/complex.

Covalent metalation of the base moieties affords a new class of modified oligonucleotides. These organometallic oligonucleotides share many properties, notably increased hybridization affinity conferred by metal-mediated base pairing, with oligonucleotides incorporating coordinative transition-metal complexes. They are, however, set apart by their ability to retain the transition-metal ion even at extreme dilution. Such stability towards dissociation would be desirable in DNA nanotechnology and necessary in therapeutic applications. Herein we describe our efforts towards preparation and characterization of covalently mercurated and palladated oligonucleotides, highlighting in particular our recent contribution on the synthesis and potential applications of oligonucleotides incorporating dimercurated artificial nucleobases.1 Introduction2 Synthesis of Covalently Mercurated and Palladated Oligonucleotides3 Hybridization Properties of Covalently Mercurated and Palladated Oligonucleotides4 Outlook

A C-nucleoside derivative of phenylpyridine or the respective palladacycle was incorporated at either 3′- or 5′-terminus of a short oligodeoxynucleotide. Hybridization properties of these modified oligonucleotides were studied in a fluorescence-based competition assay in addition to conventional UV melting temperature analysis and compared with those of a previously prepared analogue featuring the modified nucleoside in the middle of the sequence. With the unpalladated phenylpyridine oligonucleotides, UV melting temperature qualitatively correlated with the ability to displace a strand from a double helix in the competition assay, decreasing in the order 5′ > 3′ > middle. Corresponding results on the palladacyclic oligonucleotides were more difficult to interpret but both UV melting and competition experiments revealed a decrease in the duplex stability upon palladation in most cases. On the other hand, dependence of the UV melting temperature on the identity of the canonical nucleobase opposite to the modified nucleobase analogue was much more pronounced with the palladacyclic duplexes than with their unpalladated counterparts. Furthermore, UV melting profiles of the palladacyclic duplexes featured an additional transition at a temperature exceeding the melting temperature of the unmodified part of the duplex. Taken together, these results lend support to the idea of Pd(II)-mediated base pairs that are highly stable but incompatible with the geometry of a double helix.

An oligonucleotide incorporating a palladacyclic nucleobase has been prepared by ligand-directed metalation of a phenylpyridine moiety. This oligonucleotide hybridized with natural counterparts placing any of the canonical nucleobases opposite to the palladacyclic residue. The palladated duplexes had B-type conformation and melting temperatures comparable to those of respective unmodified duplexes with a single mismatch. In the duplexes placing C, G or T (but not A) opposite to the palladacyclic residue, greatly increased absorptivity suggested formation of a PdII -mediated base pair. Absorptivity and ellipticity of these duplexes persisted even at the highest temperatures applicable in Tm and CD experiments (90 °C). Evidently the PdII -mediated base pairs do not dissociate under the experimental conditions.

DNA encodes the genetic information; recently, it has also become a key player in material science. Given the specific Watson-Crick base-pairing interactions between only four types of nucleotides, well-designed DNA self-assembly can be programmable and predictable. Stem-loops, sticky ends, Holliday junctions, DNA tiles, and lattices are typical motifs for forming DNA-based structures. The oligonucleotides experience thermal annealing in a near-neutral buffer containing a divalent cation (usually Mg2+ ) to produce a variety of DNA nanostructures. These structures not only show beautiful landscape, but can also be endowed with multifaceted functionalities. This Review begins with the fundamental characterization and evolutionary trajectory of DNA-based artificial structures, but concentrates on their biomedical applications. The coverage spans from controlled drug delivery to high therapeutic profile and accurate diagnosis. A variety of DNA-based materials, including aptamers, hydrogels, origamis, and tetrahedrons, are widely utilized in different biomedical fields. In addition, to achieve better performance and functionality, material hybridization is widely witnessed, and DNA nanostructure modification is also discussed. Although there are impressive advances and high expectations, the development of DNA-based structures/technologies is still hindered by several commonly recognized challenges, such as nuclease instability, lack of pharmacokinetics data, and relatively high synthesis cost.

The present work describes efficient avenues for the synthesis of the trisaccharide repeating unit [α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap] associated with the A-band polysaccharide of Pseudomonas aeruginosa. One of the key steps involved 6-O-deoxygenation of either partially or fully acylated 4,6-O-benzylidene-1-thiomannopyranoside by radical-mediated redox rearrangement in high yields and regioselectivity. The D-rhamno-thioglycosides so obtained allowed efficient access to the trisaccharide target via stepwise glycosylation as well as a one-pot glycosylation protocol. In a different approach, a 4,6-O-benzylidene D-manno-trisaccharide derivative was synthesized, which upon global 6-O-deoxygenation followed by deprotection generated the target D-rhamno-trisaccharide. The application of the reported regioselective radical-mediated deoxygenation on 4,6-O-benzylidene D-manno thioglycoside (hitherto unexplored) has potential for ramification in the field of synthesis of oligosaccharides based on 6-deoxy hexoses.

Trichloroisocyanuric acid (TCCA), an inexpensive, commercially available, and non-toxic reagent has been used for the activation of thioglycosides toward their hydrolysis to the corresponding hemiacetals in high to excellent yields. The methodology provides a mild reaction condition for dealing with compounds containing acid sensitive functional groups.

An expeditious three-component, one-pot, sequential synthesis of a common block tetrasaccharide fragment Manp-(1→3)-Manp-(1→2)-Manp-(1→2)-Manp related to the pentasaccharide repeating unit of the O -antigen of Escherichia Coli O9, Klebsiella pneumonia O3, and Hafnia alvei PCM 1223 with minimal protecting group manipulation is reported.

Download : Download full-size image N-(p-Methylphenylthio)-e-caprolactam (1) in combination with trimethylsilyl trifluoromethanesulfonate (TMSOTf) provides an efficient thiophilic promoter system, capable of activating different thioglycosides. Both ‘armed’ and ‘disarmed’ thioglycosyl donors were activated for glycosidic bond formation. Notably, this reagent combination works well in reactivity-based one-pot oligosaccharide assembly strategy.

A convergent synthesis of the tetrasaccharide repeating unit of the O-antigenic cell wall polysaccharide of Escherichia coli 78, as the corresponding methyl glycoside (I), is being reported. It involved stereoselective glycosidation of a β-linked mannodisaccharide acceptor with a β-linked glucosamine based disaccharide thioglycoside donor, which were prepared from the corresponding functionalised monosaccharide based glycosyl donors and acceptors. The resulting tetrasaccharide derivative was finally converted to (I) by selective deprotection and also by global protection and deprotection techniques.

ZrOCl2 · 8H2O catalyzes the one-pot synthesis of β′-acetamido-β-dicarbonyl compounds in high yields from aldehyde, enolizable β-dicarbonyl compound, acetyl chloride, and acetonitrile in solvent as well as in solvent-free conditions. β′-Acetamido-β-ketoesters are formed in moderate to exclusive pref-diastereoselectivity.

NIS/TfOH mediated glycosidation of methyl 3,4,6-tri-O-benzyl-α- d -mannopyranoside with phenyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α- d -mannopyranoside furnished the corresponding disaccharide derivative in excellent yield and α-selectivity. Zemplen deacetylation of the same followed by reaction with BSP/Tf2O-preactivated phenyl 4,6-O-benzylidene-2,3-di-O-benzyl-1-thio-α- d -mannopyranoside generated methyl 4,6-O-benzylidene-2,3-di-O-benzyl-β- d -mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α- d -mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α- d -mannopyranoside in very good yield and excellent β-selectivity. Pd/C catalyzed hydrogenation of the latter finally afforded the repeating trisaccharide of Escherichia coli 8 O-antigen as its methyl glycoside.

Glycosides and thioglycosides based on monosaccharides in reaction with benzaldehyde dimethylacetal or p -methoxybenzaldehyde dimethyl acetal undergo FeCl 3 -catalyzed (20 mol %) regioselective 4,6-O-arylidenation producing the corresponding acetals in high yields. FeCl 3 also mediates acetalation of glycosides and thioglycosides of cellobiose, maltose, and lactose affording the corresponding 4′,6′- O -benzylidene acetals, which were isolated after their acetylation in situ with acetic anhydride and pyridine. The combined yields (two steps) of these final products are also high (61–84%). The procedure is applicable to a wide variety of functional groups including –OBn.

A convergent synthesis of the tetrasaccharide repeating unit of the O-antigenic cell wall polysaccharide of Escherichia coli 78, as the corresponding methyl glycoside (I), is being reported. It involved stereoselective glycosidation of a β-linked mannodisaccharide acceptor with a β-linked glucosamine based disaccharide thioglycoside donor, which were prepared from the corresponding functionalised monosaccharide based glycosyl donors and acceptors. The resulting tetrasaccharide derivative was finally converted to (I) by selective deprotection and also by global protection and deprotection techniques.

ZrOCl2 · 8H2O catalyzes the one-pot synthesis of β′-acetamido-β-dicarbonyl compounds in high yields from aldehyde, enolizable β-dicarbonyl compound, acetyl chloride, and acetonitrile in solvent as well as in solvent-free conditions. β′-Acetamido-β-ketoesters are formed in moderate to exclusive pref-diastereoselectivity.

Trichloroisocyanuric acid (TCCA), a readily available, inexpensive and shelf-stable reagent, in combination with a catalytic amount of TMSOTf, has been used for the first time for efficient glycosylation reactions based on thioglycoside donors with SEt, SPh and S-pTol leaving groups at the anomeric centres.