Kunj B. Mishra

Click Chemistry Inspired Synthesis of Morpholine-Fused Triazoles

The synthesis of triazolyl azido alcohols from terminal alkyne via oxirane ring-opening of epichlorohydrin, followed by click reaction with alkynes, and subsequent azidation of chlorohydroxy triazoles was achieved under a one-pot methodology. The developed triazolyl azido alcohols were further utilized for the synthesis of a diverse range of morpholine-fused triazoles of chemotherapeutic value. The structure of all developed compounds has been elucidated using IR, NMR, MS, and elemental analysis, where four of them have been characterized by single-crystal X-ray analysis.

Click inspired synthesis of antileishmanial triazolyl O-benzylquercetin glycoconjugates

AbstractThe 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with O-benzylquercetin alkynes (5–7) to afford regioselective triazole-linked O-benzylquercetin glycoconjugates (8–10) was investigated in the presence of CuI/DIPEA in dichloromethane. All the developed glycoconjugates (8–10) were evaluated for anti-leishmanial activity against the promastigotes and amastigotes of Leishmania donovani. Graphical AbstractClick Inspired Synthesis of Antileishmanial Triazolyl O-Benzylquercetin Glycoconjugates

Click chemistry inspired highly facile synthesis of triazolyl ethisterone glycoconjugates.

Numerous deoxy-azido sugars 3 were prepared by the reaction of tosyl/bromo sugars with NaN3 in dry DMF under heating condition. The 1,3-dipolar cycloaddition of deoxy-azido sugars 3 with ethisterone 4 to afford regioselective triazole-linked ethisterone glycoconjugates 5 was investigated in the presence of CuI and DIPEA in dichloromethane or CuSO4·5H2O and sodium ascorbate in aqueous medium. All the developed compounds were characterized by spectroscopic analysis (IR, (1)H &(13)C NMR, and MS spectra). Structure of triazolyl ethisterone glycoconjugate 5a has been further confirmed by its Single Crystal X-ray analysis.

Efficient synthesis of ethisterone glycoconjugate via bis-triazole linkage.

Synthesis of sugar based triazolyl azido-alcohols was accomplished via one pot click reaction of glycosyl alkynes with epichlorohydrin in aqueous medium. All the developed triazolyl azido-alcohols were further utilized for the synthesis of bis-triazolyl ethisterone glycoconjugates using CuAAC reaction. The developed triazole-linked ethisterone glycoconjugates would be crucial in androgen receptor pharmacology and chemical biology.

First noscapine glycoconjugates inspired by click chemistry

A number of novel 7-O-noscapine glycoconjugates have been synthesized starting from noscapine, an alkaloid found in the opium plant, via two successive steps. The first step is a selective 7-O-demethylation of noscapine and the next is a subsequent propargylation which affords 7-O-propargyl noscapine (3) in good yield. The structure was confirmed by extensive spectroscopic data including single crystal X-ray data. The 1,3-dipolar cycloaddition of the developed noscapine derivative 3 with glycosyl azides 6a–m was investigated to give the triazole-linked second-generation noscapine analogs in their glycoconjugate forms (8a–m) to augment the therapeutic efficacy of noscapine.

Synthesis, structure, and catalytic activities of new Cu(I) thiocarboxylate complexes

Thiobenzoate complexes of Cu(I), [Cu(SCOPh)]n(1), [Cu(bpy)(µ-SCOPh)]2 (2), [Cu(dppf)(SCOPh)] (3), [where bpy = 2,2′-bipyridyl; dppf = [1,1′-bis(diphenylphosphino)ferrocene] were synthesized and structurally characterized by X-ray crystallography. NBO calculations were performed to understand the nature of the Cu–Cu (2.706 A) interaction in 2. All of the complexes were found to catalyze azide–alkyne cycloaddition for the regioselective synthesis of glycoconjugate triazoles under click reaction.

Metal free synthesis of morpholine fused [5,1-c] triazolyl glycoconjugates via glycosyl azido alcohols

A series of diverse glycosyl 1,2-azido alcohols, obtained from readily available carbohydrates, were converted to structurally varied rare and novel sugar derived morpholine fused [5,1-c]-triazoles via a one-pot strategy. After incorporating a propargyl functionality at the hydroxyl group of the sugar derived 1,2-azido alcohols, the resulting in situ generated azido–alkyne affords numerous C- and O-glycosyl bicyclic ring systems with medicinal value via a metal free cycloaddition reaction. The structures of all the developed molecules have been elucidated using 1H NMR, 13C NMR, IR and MS spectroscopy.

Click inspired synthesis of triazole-linked vanillin glycoconjugates

AbstractThe 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with alkyne derivatives of p-vanillin, 3-methoxy-4-(prop-2-ynyloxy)benzaldehyde (2) and 2-methoxy-1-(prop-2-ynyloxy)-4-((prop-2-ynyloxy)methyl)benzene) (4) to afford regioselective triazole-linked vanillinglycoconjugates 5 and 6 was investigated in the presence of CuI/DIPEA in dichloromethane. All the developed glycoconjugates were characterized on the basis of IR, NMR, and MS. Graphical abstractTriazolyl vanillin glycoconjugates via click chemistry

Chapter 10 - Carbohydrate-Based Therapeutics: A Frontier in Drug Discovery and Development

Carbohydrates, one of the most abundant classes of biomolecules, are the structural building blocks of genetic materials and vital source of energy. They are integral part of the living cells as they play key roles in many cellular and intracellular interactions in the form of cell surface receptors, signaling molecules, and bacterial adhesives. These roles of carbohydrates underlie their potential as pharmaceutical and diagnostic agents and therefore stimulate the synthetic chemists to develop various facile ways to synthesize diverse eccentric glycoconjugates. Many carbohydrates and their derivatives of natural and synthetic origin are clinically used for treatment of various diseases. The immense structural diversity in terms of functional groups, linkages, and number of rings offers these molecules as a valuable tool for design and development of biologically active glycoconjugates. The promising biological activity of carbohydrate-based entities makes them valuable molecular scaffold after their thorough chemical and biological investigations. The carbohydrate moieties in glycoconjugates impart properties like hydrophilicity and decreased toxicity, which enhance the bioavailability to give the optimum pharmacokinetics. This chapter will abridge the cardinal developments in the synthesis and analysis of biologically significant carbohydrate-based molecules from the leading laboratories, highlighting the certainty of carbohydrates in creating an ideal therapeutic platform for drug discovery and development.Abstract Carbohydrates, one of the most abundant classes of biomolecules, are the structural building blocks of genetic materials and vital source of energy. They are integral part of the living cells as they play key roles in many cellular and intracellular interactions in the form of cell surface receptors, signaling molecules, and bacterial adhesives. These roles of carbohydrates underlie their potential as pharmaceutical and diagnostic agents and therefore stimulate the synthetic chemists to develop various facile ways to synthesize diverse eccentric glycoconjugates. Many carbohydrates and their derivatives of natural and synthetic origin are clinically used for treatment of various diseases. The immense structural diversity in terms of functional groups, linkages, and number of rings offers these molecules as a valuable tool for design and development of biologically active glycoconjugates. The promising biological activity of carbohydrate-based entities makes them valuable molecular scaffold after their thorough chemical and biological investigations. The carbohydrate moieties in glycoconjugates impart properties like hydrophilicity and decreased toxicity, which enhance the bioavailability to give the optimum pharmacokinetics. This chapter will abridge the cardinal developments in the synthesis and analysis of biologically significant carbohydrate-based molecules from the leading laboratories, highlighting the certainty of carbohydrates in creating an ideal therapeutic platform for drug discovery and development.