Recent Advances in Stereoselective Chemical O-Glycosylation Reactions.

Carbohydrates involving glycoconjugates play a pivotal role in many life processes. Better understanding toward glycobiological events including the structure-function relationship of these biomolecules and for diagnostic and therapeutic purposes including tailor-made vaccine development and synthesis of structurally well-defined oligosaccharides (OS) become important. Efficient chemical glycosylation in high yield and stereoselectivity is however challenging and depends on the fine tuning of a protection profile to get matching glycosyl donor-acceptor reactivity along with proper use of other important external factors like catalyst, solvent, temperature, activator, and additive. So far, many glycosylation methods have been reported including several reviews also. In the present review, we will concentrate our discussion on the recent trend on α- and ß-selective glycosylation reactions reported during the past decade.

Tracking Zone-wise perturbation during unfolding of some globular proteins using Eu(III) complex of Tetracycline as a probe exhibiting Stark splitting.

Enhanced 'Antenna effect' of a suitably designed ternary complex of Eu(III), Tetracycline hydrochloride (TC) and globular proteins viz bovine serum albumin (BSA), human serum albumin (HSA) and ß-lactoglobulin A (BLGA) in aqueous medium is employed to characterize the different partially unfolded states along with investigation of the micro- heterogeneous environment of the proteins during their stepwise unfolding. The zone-wise perturbation for the proteins upon denaturation by Urea and Guanidine hydrochloride (Gdn. HCl) is followed by the emission of Eu(III) through 'Antenna Effect' and that of the tryptophan (Trp) residues of the proteins as a function of denaturants both by steady state and time resolved emission study. With Gdn. HCl as denaturant, both BSA and BLGA show quenching of Eu(III) emission compared to pure protein while HSA exhibits an enhancement of antenna effect during unfolding as compared to that in its absence. In the presence of Urea, HSA and BSA show enhancement of antenna effect accompanied by Stark splitting of the 5D0→7F2 transition of Eu(III) although BLGA follows the similar pattern of quenching of Eu(III) emission as observed with Gdn. HCl without any Stark splitting. The proteins exhibit a two state transition with ΔGD values of ~ 2-3 kcal mol-1. Thus the use of Eu(III) emission as an efficient probe is advocating here to rationalize the microenvironment of the proteins during their stepwise unfolding.

Recent chemical syntheses of bacteria related oligosaccharides using modern expeditious approaches.

Apart from some essential and crucial roles in life processes carbohydrates also are involved in a few detrimental courses of action related to human health, like infections by pathogenic microbes, cancer metastasis, transplanted tissue rejection, etc. Regarding management of pathogenesis by microbes, keeping in mind of multi drug-resistant bacteria and epidemic or endemic incidents, preventive measure by vaccination is the best pathway as also recommended by the WHO; by vaccination, eradication of bacterial diseases is also possible. Although some valid vaccines based on attenuated bacterial cells or isolated pure polysaccharide-antigens or the corresponding conjugates thereof are available in the market for prevention of several bacterial diseases, but these are not devoid of some disadvantages also. In order to develop improved conjugate T-cell dependent vaccines oligosaccharides related to bacterial antigens are synthesized and converted to the corresponding carrier protein conjugates. Marketed Cuban Quimi-Hib is such a vaccine being used since 2004 to resist Haemophilus influenza b infections. During nearly the past two decades research is going on worldwide for improved synthesis of bacteria related oligosaccharides or polysaccharides towards development of such semisynthetic or synthetic glycoconjugate vaccines. The present dissertation is an endeavour to encompass the recent syntheses of several pathogenic bacterial oligosaccharides or polysaccharides, made during the past ten-eleven years with special reference to modern expeditious syntheses.

One-pot construction of carbohydrate scaffolds mediated by metal catalysts.

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.

An oxidodiperoxido vanadium-based artificial nuclease: DNA binding and cleavage studies.

Communicated by Ramaswamy H. Sarma.

A metal free mild and green approach for tandem opening of 4,6-O-benzylidene acetals to their corresponding 6-O-acetyl derivatives: Application in the synthesis of a trisaccharide using one-pot glycosylation reactions.

An efficient and high yielding reaction for tandem opening of 4,6-O-benzylidene derivatives (gluco, galacto, manno, 2-phthalimido-2-deoxy glucosides) to their corresponding 6-O-acetyl derivatives has been established under metal free condition using 60% solution of aqueous acetic acid (v/v). The reaction is equally pertinent for large scale synthesis and also for disaccharide glycosides. Its application for the construction of a building block towards synthesis of a trisaccharide part related to Pseudomonas aeruginosa utilizing one-pot glycosylation reactions has also been described.

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A.

Streptococcus pneumonia (SPn) is a Gram-positive bacterium which causes life threatening diseases. The bacteria protect themselves against non-specific host defence by an external polysaccharide (PS) capsule which bears a repeating unit, α-D-Galp(1->3)-α-D-Glcp(1->3)-α-L-Rhap(1->3)-D-Rib (SPn 6A). A closer look at the structure reveals the presence of α-linked galactose and glucose residues. The synthesis of these 1,2-cis glycosidic linkages are considered challenging particularly in the context of a one-pot oligosaccharide synthesis. We have synthesized the aforesaid tetrasaccharide (SPn 6A) based on both stepwise and sequential one-pot glycosylation reactions using easily accessible common building blocks; eventually similar overall yields were obtained in both cases.

Coumarin based colorimetric and fluorescence on-off chemosensor for F-, CN- and Cu2+ ions.

(E)-4-Chloro-3-[{2-(4-nitrophenyl)hydrazono}methyl]-2H-chromen-2-one (C), a coumarin derivative has been studied toward its ion sensing properties for F-, CN- and Cu2+. A proton-transfer mechanism for F- sensing has been deduced with the help of 1H NMR titration alongwith from the changes in the absorption and emission spectra of C in the presence of F-. C formed 1:1 stoichiometric complex with each of these analytes. Sensing of C toward Cu2+ is poor, but interestingly in the presence of F-or CN- the sensing ability of Cu2+ gets enhanced many folds, and C can act as F-or CN- mediated off-on sensor for Cu2+. Moreover, colorimetric strip (pre-coated with the coumarin derived compound) tests for F-and CN- from their DMSO solution at high temperature (~100°C) opens up the door for easiest naked eye recognition and distinction of these ions, and also for naked-eye detection of F- and CN- from its aqueous solution at high temperature (~100°C).

Carbohydrate Derived Organogelators and the Corresponding Functional Gels Developed in Recent Time.

Owing to their multifarious applicability, studies of molecular and supramolecular gelators and their corresponding gels have gained momentum, particularly in the last two decades. Hydrophobic⁻hydrophilic balance, different solvent parameters, gelator⁻gelator and gelator⁻solvent interactions, including different noncovalent intermolecular interactive forces like H-bonding, ionic interactions, π⁻π interactions, van der Waals interactions, etc., cause the supramolecular gel assembly of micro and nano scales with different types of morphologies, depending on the gelator, solvent, and condition of gelation. These gel structures can be utilized for making template inorganic superstructures for potential application in separation, generation of nanocomposite materials, and other applications like self-healing, controlled drug encapsulation, release and delivery, as structuring agents, oil-spill recovery, for preparation of semi-conducting fabrics, and in many other fields. Sugars, being easily available, inexpensive, and nontoxic natural resources with multi functionality and well-defined chirality are attractive starting materials for the preparation of sugar-based gelators. This review will focus on compilation of sugar derived organogelators and the corresponding gels, along with the potential applications that have been developed and published recently between January 2015 and March 2018.

Synthetic Routes toward Acidic Pentasaccharide Related to the O-Antigen of E. coli 120 Using One-Pot Sequential Glycosylation Reactions.

Concise syntheses of the acidic pentasaccharide, related to the O-antigenic polysaccharide of Escherichia coli 120, as its p-methoxyphenyl glycoside, have been achieved using a one-pot sequential glycosylation technique. The glycosylations have been accomplished either by the activation of the thioglycosides using NIS in the presence of FeCl3 or by a preactivation by Ph2SO, TTBP, Tf2O, and the activation of the trichloroacetimidates using FeCl3 alone or TMSOTf. Most of the intermediate steps are high yielding, and the stereo outcomes of the glycosylation steps were excellent. The syntheses of the targeted pentasaccharide have been performed with both three- and four-component, one-pot sequential glycosylation reactions, and in both cases, the orthogonal glycosylations are carried out utilizing catalytic activity of FeCl3. A late-stage TEMPO-mediated regioselective oxidation has been performed to achieve the required uronic acid motif.

A target oriented expeditious approach towards synthesis of certain bacterial rare sugar derivatives.

Bacterial rare amino deoxy sugars are found in the cell surface polysaccharides of multiple pathogenic bacterial strains, but are absent in the human metabolism. This helps in the differentiation between pathogens and host cells which can be exploited for target specific drug discovery and carbohydrate based vaccine development. The principal bacterial atypical sugar derivatives include 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (AAT), 2,4-diacetamido-2,4,6-trideoxy-d-galactose (DATDG) and N-acetylfucosamine (FucNAc). Herein, a highly streamlined protocol leading to the aforesaid derivatives is presented. The highlights of the method lie in radical mediated 6-deoxygenation along with a one-pot like protection profile manipulation on suitably derivatised d-glucosamine or d-mannose motifs to obtain a vital quinovosaminoside or rhamnoside from which rare sugar derivatives were synthesized in a diversity oriented manner.

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa.

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 efficient green reagent for activation of thioglycosides toward hydrolysis.

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.

A new triterpenoid saponin from Glinus oppositifolius with α-glucosidase inhibitory activity.

Evaluation of α-glucosidase inhibitory activity led to the isolation of six triterpene saponins from the aerial parts of Glinus oppositifolius including one new and five known constituents. The structure of the new saponin, glinoside C (1), was established as 16-O-(ß-D-glucopyranosyl)-3ß,12ß,16ß,21α,22-pentahydroxy hopane by extensive use of 1-D, 2-D NMR and mass spectral techniques. The other constituents identified were 3-O-(ß-D-xylopyranosyl)-spergulagenin A (2), spergulacin (3), spergulin A (4), spergulacin A (5) and spergulin B (6). Compound 1 exhibited the greatest inhibition of the enzyme with IC50 of 127 ± 30 µM. Kinetics study for the compound 1 demonstrated mixed type of inhibition (Ki = 157.9 µM).

Bio-assay guided isolation of alpha-glucosidase inhibitory constituents from Eclipta alba.

Eclipta alba (L.) Hassk is used traditionally in diabetes mellitus in India and the plant extract is reported to possess anti-diabetic activity. A bioactivity-guided isolation approach based on alpha-glucosidase inhibition was used to identify the constituents contributing towards the inhibition of the enzyme and probably contributing towards its anti-diabetic activity. Four echinocystic acid glycosides were thus isolated, of which eclalbasaponin VI, isolated from the n-butanol fraction, was found to be the most potent (IC50 54.2 +/- 1.3 microM). The compound is an uncompetitive type of inhibitor with Ki 26.1 microM. A quantitative estimation of the constituents was established using RP-HPLC.

Efficient activation of thioglycosides with N-(p-methylphenylthio)-ε-caprolactam-TMSOTf.

N-(p-Methylphenylthio)-ε-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.

FeCl3 mediated arylidenation of carbohydrates.

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.

Aryl 4,6-O-arylidene-1-thio-beta-d-glycopyranoside-based new organogelators and their gels.

Aryl 4,6-O-arylidene-1-thio-beta-d-glycopyranosides based on glucose and galactose form organogels in benzene, toluene, o- and p-xylene and 1,2,3,4-tetrahydronaphthalene. The gel morphologies of micro and nano dimensions were studied using SEM and TEM. Absorption spectroscopic studies of two organogels in benzene revealed that CH-pi or pi-stacking along with intermolecular H-bonding is responsible for the gel assembly.

Synthesis of novel aminoquinonoid analogues of diospyrin and evaluation of their inhibitory activity against murine and human cancer cells.

The synthesis and tumor-inhibitory activity of a series of aminonaphthoquinone derivatives of diospyrin, which was isolated from Diospyros montana Roxb., are presented here for the first time. An aminoacetate derivative showed the maximum (approximately 93%) increase in life span in vivo against murine Ehrlich ascites carcinoma (EAC) at a dose of 1 mg kg(-1)day(-1) (ip; five doses), and the lowest IC50 (0.06 microM) in vitro. Further, the same analogue also exhibited considerable enhancement in antiproliferative activity when evaluated against human cell lines, viz. malignant skin melanoma and epidermoid laryngeal carcinoma (IC50=0.06 and 0.92 microM, respectively) in comparison to the natural precursor, diospyrin (IC50=0.82 and 3.58 microM, respectively). Moreover, diospyrin and all its derivatives were found to show significantly greater (approximately 17- to 1441-fold) cytotoxicity against the tumor cells as compared to normal human lymphocytes. All these quinonoids generated substantial amounts of reactive oxygen species in EAC cells, more or less commensurate to their respective IC50 values.

Novel glycoconjugates of diospyrin, a quinonoid plant product: synthesis and evaluation of cytotoxicity against human malignant melanoma (A375) and laryngeal carcinoma (Hep2).

Glycoside derivatives of diospyrin (1) were synthesized for the first time, and the cytotoxicity of the novel compounds vis-à-vis their precursors were evaluated against two human cancer cell lines, viz. malignant melanoma (A375) and laryngeal carcinoma (Hep2). The IC(50) values were in the low micromolar range for all the compounds tested, and A375 cells showed comparatively greater sensitivity than Hep2. Most of the compounds exhibited enhanced activity as compared to the plant-derived quinonoid precursor of the series (1), while the aminophenyl mannosyl (6) was found to be the most effective derivative. In A375 cells, 6 (IC(50) = 0.02 microM) showed the maximum increase in cytotoxicity (approximately 35-fold) over that of 1 (IC(50) = 0.82 microM). Again, when the glycosides were evaluated at a given concentration (0.1 microM) for their relative capacity to generate ROS from A375 cells, the compound 6 could produce the highest amount of ROS. Incidentally, this derivative also showed a comparatively lower toxicity (IC(50) approximately 41 microM) when tested against normal human peripheral blood mononuclear cells, indicating a fair prospect of its development as a novel chemotherapeutic agent for the treatment of malignant melanoma.