Tanmaya Pathak

Regioselectivity of Vinyl Sulfone Based 1,3-Dipolar Cycloaddition Reactions with Sugar Azides by Computational and Experimental Studies

DFT (M06-L) calculations on the transition state for the 1,3-dipolar cycloadditions between substituted vinyl sulfones with sugar azide have been reported in conjunction with new experimental results, and the origin of reversal of regioselectivity has been revealed using a distortion/interaction model. This study provides the scientific justification for combining organic azides with two different types of vinyl sulfones for the preparation of 1,5-disubstituted 1,2,3-triazoles and 1,4-disubstituted triazolyl esters under metal-free conditions.

1,5-disubstituted 1,2,3-triazolylation at C1, C2, C3, C4, and C6 of pyranosides: a metal-free route to triazolylated monosaccharides and triazole-linked disaccharides.

A pair of easily accessible vinyl sulfones derived from styrene epoxide and monotosylated glycerol were reacted with six different azidopyranosides having an azido group at C1, C2, C3, C4, C6, and at the terminal position of an exocylic chain attached to C1. The reaction was performed mostly in water at elevated temperature without any metal catalyst to afford regioselectively 1,5-disubstituted triazolylated pyranosides in high yields. Another set of exocyclic vinyl sulfones prepared from 3-O-methylated- and 3-O-benzylated glucofuranosides as well as 3-O-benzylated allofuranoside were also subjected to 1,3-dipolar cycloaddition reactions with six azidopyranosides under similar reaction conditions to generate a series of 1,5-disubstituted triazole-linked disaccharides. The synthesis of all 1,5-disubstituted triazolylated monosaccharides as well as all 1,5-disubstituted triazole linked disaccharides are reported for the first time. Steric bulk around the azido and vinyl sulfone groups plays a significant role in deciding the outcome of the reactions. This powerful and practical route has the potential to be exploited for the synthesis of complex 1,5-disubstituted 1,2,3-triazolylated carbohydrates.

A vinyl sulfone-modified carbohydrate mediated new route to aminosugars and branched-chain sugars

This minireview describes syntheses of various vinyl sulfone-modified carbohydrates and their reactions with nitrogen and carbon nucleophiles for accessing a wide range of aminosugars and branched-chain sugars.

Enzymes and protecting group chemistry

Enzymatic protecting group techniques are increasingly finding their use in almost all areas of synthetic organic chemistry. Some of the recent papers have dealt with the use of such protecting groups in combination with classical methods. The modification of known protecting groups to increase the efficiency and selectivity of deprotection is on the rise. The methodology needs to be explored more intensively and systematically to realise its full potential.

A general route to 1,5-disubstituted 1,2,3-triazoles with alkyl/alkyl, alkyl/aryl, aryl/aryl combinations: a metal-free, regioselective, one-pot three component approach

An experimentally simple one-pot reaction, affording 1,5-disubstituted 1H-1,2,3-triazoles in good to excellent yields by combining vinyl sulfones, sodium azide and alkyl bromides, -tosylates, -mesylates or aryl amines, -iodides is reported. The organic azides, generated in situ react with vinyl sulfones in a regioselective fashion in the absence of metal ions. Unlike many of the recently reported strategies, this method is capable of generating alkyl/alkyl, alkyl/aryl and aryl/aryl containing 1,5-disubstituted 1,2,3-triazoles under simple reaction conditions.

Vinylsulfone-modified carbohydrates: first general route to D-lividosamine (2-amino-2,3-dideoxy-D-glucose) and its new analogues

Abstract A general route to d -lividosamine and its new analogues has been devised for the first time. The essence of the present synthetic route lies in the diastereoselective introduction of N-monoalkylated and N-dialkylated amines to C-2 carbons of methyl 2,3-dideoxy-3-C-phenylsulfonyl-α- d -hex-2-enopyranoside and methyl 2,3-dideoxy-3-C-phenylsulfonyl-β- d -hex-2-enopyranoside in equatorial configurations. The 2-amino-2,3-dideoxysugrs thus generated, are desulfonated reductively at C-3 sites to produce a known intermediate for the synthesis of d -lividosamine and several new 2-N-alkylamino- and 2-N,N-dialkylamino-2,3-dideoxy analogues.

Synthesis of anomerically pure vinyl sulfone-modified pent-2-enofuranosides and hex-2-enopyranosides: a group of highly reactive Michael acceptors for accessing carbohydrate based synthons

Abstract Syntheses of the benzyl or the trityl protected α- and β-anomers of vinyl sulfone-modified pent-2-enofuranosides have been initiated by the ring opening of the suitably masked methyl α- lyxo furanosyl-epoxide or methyl β- ribo furanosyl-epoxide or by the nucleophilic displacement of the leaving groups in benzyl protected 3- O -tosyl xylo furanoside and 3- O -mesyl ribo furanoside by p -thiocresol. In case of the latter set of starting materials, α- and β-methyl glycosides formed in almost equal ratio only from the derivatives of d -xylose. For the synthesis of α- and β-anomers of vinyl sulfone-modified hex-2-enopyranosides, a d -glucose derivative was selected over a d -allose derivative as the starting material because the former almost exclusively produced the required methyl pyranosides whereas the latter produced a mixture. All sulfides were converted to vinyl sulfone-modified carbohydrates by the sequential application of oxidation, mesylation and base induced elimination reactions.

Enantiopure 1,4,5-trisubstituted 1,2,3-triazoles from carbohydrates: applications of organoselenium chemistry.

A wide range of stable vinyl selenone-modified furanosides has been synthesized for the first time. These 2π-partners undergo 1,3-dipolar cycloaddition reactions with a wide range of organic azides to afford enantiopure trisubstituted triazoles. Furanosyl rings opened up during triazole synthesis to generate polyfunctionalized molecules, ready to undergo further transformations. This strategy is one of the most convenient methods for the synthesis of enantiopure 1,4,5-trisubstituted 1,2,3-triazoles where the chiral components are attached to C-4 or C-5 position of triazole ring. These triazoles are formed in a regioselective manner, and several pairs of regioisomeric triazoles have also been synthesized. The approach affords densely functionalized triazoles, which are amenable to further modifications because of the presence of aldehyde and hydroxyl groups. This powerful and practical route adds to the arsenals of chemists and biologists interested in the synthesis and applications of triazoles.

Densely Functionalized Chiral Pyrroles from Endocyclic, Exocyclic, and Acyclic Vinyl Sulfone-Modified Carbohydrates

A wide range of vinyl sulfone-modified carbohydrates have been prepared as starting materials for the synthesis of polysubstituted chiral pyrroles. All these vinyl sulfones reacted efficiently with ethylisocyanoacetate to generate a plethora of new pyrrole derivatives. Furanosyl rings opened up during pyrrole synthesis, and pyranosyl rings were opened up by reacting the pyrrole with POCl(3)/DMF. This paper also reports one of the most efficient and practical routes for the synthesis of beta-substituted pyrroles.

Dinucleosides with Non-Natural Backbones: A New Class of Ribonuclease A and Angiogenin Inhibitors

Ribonuclease A (RNase A) serves as a convenient model enzyme in the identification and development of inhibitors of proteins that are members of the ribonuclease superfamily. This is principally because the biological activity of these proteins, such as angiogenin, is linked to their catalytic ribonucleolytic activity. In an attempt to inhibit the biological activity of angiogenin, which involves new blood vessel formation, we employed different dinucleosides with varied non-natural backbones. These compounds were synthesized by coupling aminonucleosides with dicarboxylic acids and amino- and carboxynucleosides with an amino acid. These molecules show competitive inhibition with inhibition constant (K(i)) values of (59±3) and (155±5) μM for RNase A. The compounds were also found to inhibit angiogenin in a competitive fashion with corresponding K(i) values in the micromolar range. The presence of an additional polar group attached to the backbone of dinucleosides was found to be responsible for the tight binding with both proteins. The specificity of different ribonucleolytic subsites were found to be altered because of the incorporation of a non-natural backbone in between the two nucleosidic moieties. In spite of the replacement of the phosphate group by non-natural linkers, these molecules were found to selectively interact with the ribonucleolytic site residues of angiogenin, whereas the cell binding site and nuclear translocation site residues remain unperturbed. Docked conformations of the synthesized compounds with RNase A and angiogenin suggest a binding preference for the thymine-adenine pair over the thymine-thymine pair.