Tamashree Ghosh

Removal of benzylidene acetal and benzyl ether in carbohydrate derivatives using triethylsilane and Pd/C.

Summary Clean deprotection of carbohydrate derivatives containing benzylidene acetals and benzyl ethers was achieved under catalytic transfer hydrogenation conditions by using a combination of triethylsilane and 10% Pd/C in CH3OH at room temperature. A variety of carbohydrate diol derivatives were prepared from their benzylidene derivatives in excellent yield.

Oxidative stress plays major role in mediating apoptosis in filarial nematode Setaria cervi in the presence of trans-stilbene derivatives

Lymphatic filariasis, affecting around 120 million people in 80 countries worldwide, is an extremely painful disease and caused permanent and long term disability. Owing to its alarming prevalence there is immediate need for development of new therapeutics. A series of trans-stilbene derivatives were synthesized using aqueous reaction condition showing potential as antifilarial agents demonstrated in vitro. MTT reduction assay and dye exclusion test were performed to evaluate the micro and macrofilaricidal potential of these compounds. Amid 20 trans-stilbene derivatives together with Resveratrol (RSV), a multifunctional natural product was screened; nine compounds (28, 29, 33, 35, 36, 38, 39, 41 and 42) have showed promising micro and macrofilaricidal activities and four of them (28, 39, 41 and 42) showed better effectiveness than RSV. In the treated parasites apoptosis was established by DNA laddering, in situ DNA fragmentation and FACS analysis. The generation of ROS in the treated parasites was indicated by the depletion in the level of GSH, GR and GST activity and elevation of SOD, catalase, GPx activity and superoxide anion and H2O2 level. Along with the ROS generation and oxidative stress, the decreased expression of anti-apoptotic ced-9 gene and increased expression of nematode specific pro-apoptotic genes, egl-1, ced-4 and ced-3 at the level of transcription and translation level; the up-regulation of caspase-3 activity and involvement of caspase-8,9,3, cytochrome-c and PARP were also observed and which denotes the probable existence of both extrinsic and intrinsic pathways apoptosis in parasitic nematodes. This observation is reported first time and thus it confirmed the mode of action and effectiveness of the compounds. Further, the comparative bioavailability-pharmacokinetics studies showed that compound 28 possesses comparable properties with Ivermectin. This study will certainly intensify our understanding of the pharmacological importance of trans-stilbenes as an anti-filarial agent.

Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

Summary A series of glycosyl hemiacetal derivatives have been transformed into thioglycosides and glycosyl thiols in a one-pot two-step reaction sequence mediated by Appel reagent (carbon tetrabromide and triphenylphosphine). 1,2-trans-Thioglycosides and β-glycosyl thiol derivatives were stereoselectively formed by the reaction of the in situ generated glycosyl bromides with thiols and sodium carbonotrithioate. The reaction conditions are reasonably simple and yields were very good.

Convergent synthesis of a hexasaccharide corresponding to the cell wall O-antigen of Escherichia coli O41

A convergent synthetic strategy has been developed for the synthesis of a hexasaccharide corresponding to the O-antigen of E. coli O41 using stereoselective [3 + 3] block glycosylation strategy. The target compound was synthesized assembling a series of suitably protected monosaccharide intermediates. Thioglycoside derivatives have been used as glycosyl donors in most of the glycosylation reactions. All intermediate steps are high yielding and the glycosylation steps are highly stereoselective. A number of recently developed methodologies have been used in the synthesis.

Facile synthesis of the pentasaccharide repeating unit of the cell wall O-antigen of Escherichia coli 19ab

A straightforward synthesis of the pentasaccharide with all α-linked glycosyl linkages corresponding to the cell wall O-antigen of Escherichia coli 19ab has been achieved in excellent yield using sequential glycosylations of monosaccharide intermediates. The structure of the target compound and its synthetic intermediates were unambiguously characterized using their spectral analysis. A generalized glycosylation condition has been used in all glycosylations and minimum number of protecting group manipulations were involved during the synthesis of the target compound.

Efficient synthesis of the tetrasaccharide repeating unit of the O-antigen of Escherichia coli O174 strain

The tetrasaccharide repeating unit of the O-antigen of Escherichia coli O174 strain was synthesized applying sequential glycosylations of suitably functionalized monosaccharide intermediates. Activation of glycosyl trichloroacetimidate derivatives using nitrosyl tetrafluoroborate (NOBF4) has been used during the synthesis. The glycosylation steps were high yielding with satisfactory stereo outcome.

Synthesis of the Heptasaccharide Repeating Unit of the Cell Wall O‐Polysaccharide of Enterotoxigenic Escherichia coli O139

Abstract Enterotoxigenic Escherichia coli (ETEC) like the O139 strain are mostly responsible for travelers diarrhea and causes diseases in pigs, cattle, and poultry. A convenient synthetic strategy was developed for the synthesis of the heptasaccharide repeating unit of the cell wall lipopolysaccharide of the E. coli O139 strain. The p‐methoxybenzyl (PMB) group was used as a temporary protecting group which was removed in situ under the glycosylation conditions by changing the reaction temperature during the synthesis of the target compound. All glycosylation steps gave high yields with good stereoselectivity. A (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO)‐mediated selective oxidation of the primary hydroxyl group was carried out using a biphasic reaction condition at the late stage of the synthesis. Such synthetic oligosaccharides could later be effectively conjugated with proteins to prepare glycoconjugate derivatives as vaccine candidates.

Synthesis of Di- and Trisaccharides Related to the O-Polysaccharide of Shigella dysenteriae Type 8

GRAPHICAL ABSTRACT A disaccharide and a trisaccharide fragment related to the cell wall O-polysaccharide of Shigella dysenteriae type 8 have been synthesized in a minimum number of steps using recently reported reaction conditions. Stereoselective 1,2-cis glycosylation and late-stage selective oxidation of the primary hydroxyl group to the carboxylic group are key features of the synthetic strategy. The yields of the glycosylation reactions are excellent with high stereoselectivity.