Browsing by Author "Sumit K. Singh"

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An Improved Synthesis of Urea Derivatives from N -Acylbenzotriazole via Curtius Rearrangement
(Georg Thieme Verlag, 2019) Anoop S. Singh; Anand K. Agrahari; Sumit K. Singh; Mangal S. Yadav; Vinod K. Tiwari
The good leaving tendency of the benzotriazole moiety has been exploited for the synthesis of symmetric, unsymmetric, N -acyl, and cyclic ureas in good yields from N -acylbenzotriazoles by treating the latter with various amines in the presence of TMSN 3 /Et 3 N in a sealed tube. The salient features of the devised protocol includes the high-yield, mild, metal-free, one-pot reaction conditions, and short reaction time. Furthermore, in many cases, no column chromatography is required for the purification. © Georg Thieme Verlag Stuttgart New York.
Carbo-click in drug discovery and development: Opportunities and challenges
(Elsevier, 2020) Divya Kushwaha; Sumit K. Singh; Vinod Kumar Tiwari
Cu(I)-Catalyzed click reaction of organic azide and terminal alkyne has been identified as one of the most facile and reliable strategy for the ready construction of diversely functionalized molecules. This highly efficient protocol regioselectively produces 1, 4-disubstituted 1, 2, 3-triazole under mild reaction conditions, which is well known heterocycle for its pharmacological properties. The compatibility of click reaction with carbohydrates has enabled the synthesis of diverse glycoconjugates and thus, speeded up the process of drug discovery and development in the area of glycoscience. This chapter surveys the recent applications of click chemistry in the development of carbohydrate-based therapeutics. © 2020 Elsevier Inc. All rights reserved.
Click Chemistry
(Springer Nature, 2024) Vinod K. Tiwari; Manoj K. Jaiswal; Sanchayita Rajkhowa; Sumit K. Singh
This book comprehensively covers the fundamentals and latest advancements in the area of click chemistry. It discusses notable applications of click chemistry in various emerging areas ranging from chemical biology to catalysis and from medicinal chemistry to material sciences. Various topics covered in this book are catalysis in regioselectivity in click chemistry, organocatalysis in triazole synthesis, Bertozzi’s Bioorthogonal Concept, photo-triggered click chemistry, SuFFEx Click, Thiol-Ene Click, MCR Click, Intramolecular Click Chemistry, synthesis of diverse triazoles and their applications, Click's Post Functionalization, etc. The book is a valuable reference for beginners, researchers and professionals interested in sustainable click concept and its diverse applications in allied fields. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2024.
Click Inspired Synthesis of Novel Cinchonidine Glycoconjugates as Promising Plasmepsin Inhibitors
(Nature Research, 2020) Nidhi Mishra; Anand K. Agrahari; Priyanka Bose; Sumit K. Singh; Anoop S. Singh; Vinod K. Tiwari
Among all the malaria parasites, P. falciparum is the most predominant species which has developed drug resistance against most of the commercial anti-malarial drugs. Thus, finding a new molecule for the inhibition of enzymes of P. falciparum is the pharmacological challenge in present era. Herein, ten novel molecules have been designed with an amalgamation of cinchonidine, carbohydrate moiety and triazole ring by utilizing copper-catalyzed click reaction of cinchonidine-derived azide and clickable glycosyl alkynes. The molecular docking of developed molecules showed promising results for plasmepsin inhibition in the form of effective binding with target proteins. © 2020, The Author(s).
Cycloelimination-assisted combinatorial synthesis of diverse heterocyclic scaffolds of chemotherapeutic values
(Bentham Science Publishers, 2019) Virendra Prasad; Nidhi Mishra; Anand K. Agrahari; Sumit K. Singh; Prabhu P. Mohapatra; Vinod K. Tiwari
Recent advances in high-throughput, automated techniques combined with the identification of new therapeutic targets in genome sequencing and molecular biology have generated a need for a large collection of diverse heterocyclic scaffolds. This inspires toward the development of novel reaction sequences and linking strategies to generate libraries of diverse simple to complex heterocyclic systems. In this regard, combinatorial chemistry has emerged as an excellent technology platform for the rapid assembly of building blocks to synthesize complex molecular structures with great ease in a few synthetic steps. By means of the implementation of high-throughput screening for the biological evaluation of hits and leads, combinatorial libraries have become important assets in drug discovery and development. In the last two decades, the cyclorelease strategy that minimizes the chemical and tethering implications by releasing the intact desired target molecule in the final step of reaction has attracted much attention. Recently, a particular interest is developing in linking strategies, where loading and cleavage steps contribute to the complexity of the target structure rather than only extraneous manipulations. This review summarises the practical and high-yielding approaches of solid phase combinatorial synthesis for diverse high-purity heterocyclic skeletons of pharmacological importance involving the cycloelimination strategy. © 2019 Bentham Science Publishers.
d-Glucosamine as the Green Ligand for Cu(I)-Catalyzed Regio- And Stereoselective Domino Synthesis of (Z)-3-Methyleneisoindoline-1-ones and (E)- N-Aryl-4 H-thiochromen-4-imines
(American Chemical Society, 2021) Sumit K. Singh; Mangal S. Yadav; Anoop S. Singh; Anand K. Agrahari; Nidhi Mishra; Sunil Kumar; Vinod K. Tiwari
d-Glucosamine, a natural, inexpensive, and conveniently accessible sugar, has been explored as an efficient ligand for the Cu(I)-catalyzed regio- and stereoselective synthesis of an array of (Z)-3-methyleneisoindoline-1-ones and (E)-N-aryl-4H-thiochromen-4-imines in good-to-excellent yield in a tandem fashion via the reaction of 2-halobenzamide and 2-halobenzothioamide with terminal alkynes, respectively. The water solubility and biocompatible nature of the ligand offer easy separation of the catalytic system toward the aqueous phase as well as change in the reaction path in terms of the product also demonstrated the variation of the reaction temperature. The domino reaction proceeds by the Sonogashira and Ullmann type cross-coupling reaction, followed by Cu(I)-promoted additive cyclization of heteroatom to the triple bond. In addition, d-glucosamine causes successful Glaser-Hay coupling of terminal alkynes under Cu catalysis to produce a high yield of respective 1,3-diynes. © 2021 The Authors. Published by American Chemical Society.
Design, Synthesis and Pharmacological Evaluation of Noscapine Glycoconjugates
(Wiley-Blackwell, 2019) Kunj B Mishra; Neeraj Tiwari; Priyanka Bose; Rajan Singh; Arun K Rawat; Sumit K. Singh; Ram C. Mishra; Rakesh K Singh; Vinod K. Tiwari
The present work is directed to design a series of molecules which are hybrids of two non-toxic biocompatible chemical architectures, noscapine and carbohydrates. Fourteen, 7-O-noscapine analogues have been synthesized out of which one of the analogue is 7-O-propargylated derivative and others are in its glycoconjugate form with triazole bridging achieved via Click reaction, where dinuclear copper(I) thiodiacetate complex [(PPh 3 ) 2 Cu(μ-tda)Cu(PPh 3 ) 2 ].6H 2 O has been emerged as an excellent catalyst for the noscapine-glyco Click-coupling. All the developed noscapine glycoconjugates have been investigated for anticancer activity using HeLa cell line and anti-leishmanial activity against Leishmania donovani. Result indicates that five of the developed noscapine glycoconjugates (5 a, 5 b, 5 c, 5 e and 5 l) showed significant anti-proliferative activity. On the other hand, four of them (5 b, 5 c, 5 e, and 5 l) showed significant anti-leishmanial activity. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Glycosyl Triazole Based Pyridinamide/CuI-Catalyzed Coupling of 2-Halobenzamides with Active Methylene Compounds
(Georg Thieme Verlag, 2023) Sumit K. Singh; Sunil Kumar; Mangal S. Yadav; Subrato Bhattacharya; Vinod K. Tiwari
This report describes a convenient method for the Cu(I)- catalyzed tandem synthesis of dihydrophenanthridinediones and substituted isoquinolinones with the assistance of efficient glycosyl 1,2,3-triazole-based pyridinamide ligands. The catalytic system effectively works for the coupling of N-substituted 2-halobenzamides with various active methylene compounds to form biologically relevant heterocyclic scaffolds in high to excellent yields. The consecutive path of the reaction including intermolecular C C cross-coupling followed by intramolecular cyclization efficiently takes place at low catalytic loading. These glycosyl triazole-appended pyridinamides were synthesized in good yields by a CuI/DIPEA-mediated regioselective CuAAC click reaction. The notable features of the method include low catalytic loading, the use of cost-effective and biocompatible ligands, high reaction yield, and easily accessible starting materials that make the protocol more versatile. © 2023 Georg Thieme Verlag. All rights reserved.
Glycosyl Triazole Ligand for Temperature-Dependent Competitive Reactions of Cu-Catalyzed Sonogashira Coupling and Glaser Coupling
(American Chemical Society, 2021) Nidhi Mishra; Sumit K. Singh; Anoop S. Singh; Anand K. Agrahari; Vinod K. Tiwari
Glycosyl triazoles have been introduced as efficient ligands for the Cu-catalyzed Sonogashira reaction to overcome the challenges of sideways homocoupling reactions in Cu catalysis in this reaction. The atmospheric oxygen in a sealed tube did not affect the coupling, and no need of complete exclusion of oxygen was experienced in the presence of glycohybrid triazole ligand L3. High product yields were obtained at 130 °C for a variety of substrates including aliphatic and aromatic terminal alkynes and differently substituted aromatic halides including 9-bromo noscapine. In contrast, at room temperature, a very low loading of the L3-Cu catalytic system could produce excellent yields in Glaser coupling including homocoupling and heterocoupling of a variety of aliphatic and aromatic alkynes. © 2021 American Chemical Society
Growing Impact of Carbohydrate-Based Organocatalysts
(John Wiley and Sons Inc, 2022) Sumit K. Singh; Nidhi Mishra; Sunil Kumar; Manoj K. Jaiswal; Vinod K. Tiwari
Organocatalysis has emerged as one of the most progressive and prevailing field of organic synthesis to assist green chemistry. Constantly increasing demand of promising scaffolds to develop potent organocatalysts has impelled researchers to utilize the unique traits of carbohydrate moiety in this field. Biological significance of carbohydrates, as well as, their high natural abundance as chiral non-racemic material, presence of multiple hydroxyl groups, several stereogenic centres, and easily modifiable structure make this moiety an appropriate skeleton to develop organocatalysts to enhance productivity and selectivity of a chemical transformation. 21st Century has witnessed the progress of carbohydrate moiety in development of organocatalysts from obscurity to eminence. This review encapsulates the importance of carbohydrate scaffolds in organocatalysis mainly dealing with the synthesis and applications carbohydrate-derived organocatalyst in different common organic reactions with their significance and future purspectives. © 2022 Wiley-VCH GmbH.
Growing impact of sialic acid-containing glycans in future drug discovery
(Elsevier Ltd, 2023) Priyanka Bose; Manoj K. Jaiswal; Sumit K. Singh; Rakesh K. Singh; Vinod K. Tiwari
In nature, almost all cells are covered with a complex array of glycan chain namely sialic acids or nuraminic acids, a negatively charged nine carbon sugars which is considered for their great therapeutic importance since long back. Owing to its presence at the terminal end of lipid bilayer (commonly known as terminal sugars), the well-defined sialosides or sialoconjugates have served pivotal role on the cell surfaces and thus, the sialic acid-containing glycans can modulate and mediate a number of imperative cellular interactions. Understanding of the sialo-protein interaction and their roles in vertebrates in regard of normal physiology, pathological variance, and evolution has indeed a noteworthy journey in medicine. In this tutorial review, we present a concise overview about the structure, linkages in chemical diversity, biological significance followed by chemical and enzymatic modification/synthesis of sialic acid containing glycans. A more focus is attempted about the recent advances, opportunity, and more over growing impact of sialosides and sialoconjugates in future drug discovery and development. © 2023 Elsevier Ltd
Multicomponent Click Reaction: An Indispensable Tool for Easy Access of Functionalized 1,2,3-Triazoles
(John Wiley and Sons Inc, 2024) Mangal S. Yadav; Sanchayita Rajkhowa; Sumit K. Singh; Manoj K. Jaiswal; Vinod K. Tiwari
Multicomponent reactions are operationally simple and display a significant role in diverse chemical modification by reducing reaction times as well as additional steps involved. In this review, we highlighted the impact of multi-component reactions in assistance with modular Click chemistry to develop a library of triazole-appended scaffolds including 1,2,3-triazole-fused heterocycles, glycoconjugates, macrocycles as well as in the combinatorial synthesis of differently functionalized triazoles along with mechanistic insights with a diverse range of applications in the field of medicinal chemistry. © 2024 Wiley-VCH GmbH.
One-pot expeditious synthesis of glycosylated esters through activation of carboxylic acids using trichloroacetonitrile
(Elsevier Ltd, 2022) Mangal S. Yadav; Manoj K. Jaiswal; Sunil Kumar; Sumit K. Singh; Faisal J. Ansari; Vinod K. Tiwari
Acetimidates, a valuable intermediate has been well explored as versatile synthon in a number of organic transformations particularly as suitable donors in glycosylation reactions. Herein, we explored acetimidates to furnish high-to-excellent yield of diverse glycosylated esters under one-pot mild reaction condition. The commercially available trichloroacetonitrile is implemented for the activation of carboxylic acid via in situ generation of trichloroacetimidate, which was subsequently attacked by sugar alcohols to deliver high-to-excellent yields of desired glycosylated esters. The devised method has some notable features such as metal-free condition, one-pot mild reaction condition, easy-handling, high-to-excellent yields, and broad substrate scope. © 2022 Elsevier Ltd
Pristine NiMOF Sandwiched between 1D and 3D Engineered Au Particles and Dendrites for Ultraswift Folic Acid Sensing in Cellular Microenvironment
(American Chemical Society, 2024) N. Shubhangi; Rohini Kumari; Kajal Kachhawaha; Sumit K. Singh; Sanjay Kumar Rai; Pranjal Chandra
Catalytic metal-organic frameworks (MOFs)-based sensor matrices can act synergistically with Au metallic nanostructures to generate amplified signal readouts by causing the electro-oxidation of the target analyte. Folic acid (FA), an essential water-soluble vitamin and a precursor for enzymes, requires timely and precise monitoring in the serum of individuals with varying clinical diagnoses. An attempt has been made in this direction through our work, where the rapid detection of FA through its oxidation at metal centers from hybrid nanomaterials is deployed for signal generation. A nonenzymatic, nonimmunometric approach involving a sandwich model, comprising NiMOF layered between gold nanoparticles (AuNPs) and gold nanodendrites (AuNDs) incorporated within a sensor matrix, has been deployed for this purpose. The probe displayed great analytical performance with a linear dynamic range (LDR) from 1 × 10-11 M to 1 × 10-3 M and a limit of detection (LOD) of 0.43 × 10-11 M. The probe’s average response time with respect to changes in FA concentration was recorded as less than 2.1 s, making it a rapid sensing platform for FA detection. The real-life applicability of the developed sensor was tested in serum, followed by analysis in a breast cancer cellular microenvironment, which yielded a current recovery between 95.11 and 98.17%. The in vitro analysis was further validated through live-cell imaging using the standard method of fluorescence. The shorter fabrication time of the developed sensor compared to existing ones makes it a facile and efficient sensing platform for FA detection in clinical settings. This study represents the first report on the conjunction of 1D, 2D, and 3D materials as a sensing matrix for molecular detection applications. © 2024 American Chemical Society.
Pyridyl Glycosyl Triazole/CuI-Mediated Domino/Tandem Synthesis of Quinazolinones
(American Chemical Society, 2022) Sumit K. Singh; Sunil Kumar; Mangal S. Yadav; Vinod K. Tiwari
The glycosyl 1,2,3-triazoles are expediently accessible from readily available sugar-derived glycosyl azide by utilizing modular CuAAC "Click Chemistry", and the resulting glycohybrid skeleton possesses efficient metal-coordinating centers that support a wide range of metal-mediated efficient catalysis in various imperative organic transformations. Here, we designed and developed pyridyl glycosyl triazoles by employing the CuAAC reaction of d-glucose-derived glycosyl azides and alkynyl pyridines. These pyridyl glycosyl triazoles with Cu(I) salt were explored as an efficient catalyst to successfully assemble 2-amino-3-substituted and 3-substituted quinazolinones by the domino/tandem cross-coupling reaction of various N-substituted o-halobenzamides with cyanamide and formamide, respectively. The devised protocol has some notable features, including biocompatibility, low cost, easily accessible starting materials for the glycosyl ligands, high yield, broad spectrum, low catalytic loading, and mild reaction conditions. © 2022 American Chemical Society. All rights reserved.
Recent developments on ionic liquids-mediated synthetic protocols for biologically relevant five- and six-membered heterocyclic skeletons
(Elsevier, 2021) Priyanka Bose; Anand K. Agrahari; Sumit K. Singh; Anoop S. Singh; Mangal S. Yadav; Sanchayita Rajkhowa; Vinod K. Tiwari
More than two decades have passed with the glorified research works in the field of ionic liquids (ILs), and the explorartion is still counting by varying research groups across the world. ILs find versatile applications in organic synthesis as solvents, reaction media, and catalysts. The eye-catching advantages of ILs include easy handling, green approach, adjustable-desired physico-chemical properties, and versatile applications in preestablished reactions with much more cost-effective manner. Applications of ILs in developing suitable protocols for the syntheses of different heterocyclic skeletons have been explored with much positivity in the recent past. Among heterocycles, particularly five- and six-membered heterocycles are in the lime-light of medicinal chemistry for pharmacological activities and investigations. This chapter focuses on the properties and wide-spread applications of versatile ILs in the syntheses of heterocyclic scaffolds of promising pharmacological potential. © 2021 Elsevier Inc. All rights reserved.
Substrate-Dependent Stereoselective Synthesis of Pyrrolo[3,4-b]Pyridin-5-Ones and Pyridyl Isoindoline-1-Ones Using Bis(benzotriazol-1-yl) Ligand
(John Wiley and Sons Ltd, 2024) Mangal S. Yadav; Manoj K. Jaiswal; Sunil Kumar; Sumit K. Singh; Somenath Garai; Vinod K. Tiwari
The documented work highlighted the synthesis of bis(benzotriazol-1-yl) methane derivatives using silicomolybdic acid (SMA) and successfully implemented in the stereoselective synthesis of diverse pyrrolo[3,4-b]pyridin-5-one and pyridyl isoindolinones derivatives in one-pot. The pyridinamide precursor with diverse alkynes furnished Z-selectivity of pyrrolo[3,4-b]pyridin-5-one across exocyclic C=C bond while the various benzamides on treating with 2-ethynyl pyridine afforded (E)-pyridylisoindoline-1-ones as a major isomer. The single-crystal X-ray diffraction provides strong evidence in favor of the existence and orientation of developed compounds. The broad substrate scope, easy accessibility of substrates, high stereoselectivity, scale-up synthesis, and crystal evidence demonstrate the merits of the current decorum. © 2024 Wiley-VCH GmbH.
Synthesis of Benz-Fused Azoles via C-Heteroatom Coupling Reactions Catalyzed by Cu(I) in the Presence of Glycosyltriazole Ligands
(American Chemical Society, 2019) Nidhi Mishra; Anoop S. Singh; Anand K. Agrahari; Sumit K. Singh; Mala Singh; Vinod K. Tiwari
Glycosyl triazoles are conveniently accessible and contain multiple metal-binding units that may assist in metal-mediated catalysis. Azide derivatives of d-glucose have been converted to their respective aryltriazoles and screened as ligands for the synthesis of 2-substituted benz-fused azoles and benzimidazoquinazolinones by Cu-catalyzed intramolecular Ullmann type C-heteroatom coupling. Good to excellent yields for a variety of benz-fused heterocyles were obtained for this readily accessible catalytic system. © Copyright 2019 American Chemical Society.
Synthesis of Calix[4]arene Appended Lactosylated G1 and Galacto sylated G2 Generation Glycodendrimers using a 'CuAAC' Click Approach
(Georg Thieme Verlag, 2023) Sunil Kumar; Mangal S. Yadav; Sumit K. Singh; Sanchayita Rajkhowa; Vinod K. Tiwari
A modular and highly reliable click approach is applied for the expeditious synthesis of lactose- and galactose-coated calixarenecored G1 and G2 generation glycodendrimers, respectively. The developed calixarene glycodendrimers have been characterized by using extensive spectral analysis including NMR (1H and 13C), MS, IR, and SEC data. © 2023. The Author(s).
Triazole-Appended Glycohybrid/CuI-Catalyzed C-C Cross-Coupling of Aryl/Heteroaryl Halides with Alkynyl Sugars
(American Chemical Society, 2023) Sumit K. Singh; Sunil Kumar; Mangal S. Yadav; Abhishek Gupta; Vinod K. Tiwari
This report describes a convenient method for the Cu(I)-catalyzed Sonogashira cross-coupling reaction of aryl/heteroaryl halides and alkynyl sugars in the presence of a 1,2,3-triazole-appended glycohybrid as a biocompatible ligand. The Sonogashira cross-coupling products were exclusively formed without the Glaser-Hay homocoupling reaction in the presence of a glycosyl monotriazolyl ligand at 120 °C. However, the Glaser-Hay homocoupling products were obtained at 60-70 °C in the presence of bis-triazolyl-based macrocyclic glycohybrid ligand L8. The glycosyl triazole ligands were synthesized via the CuI/DIPEA-mediated regioselective CuAAC click reaction, and a series of glycohybrids of glucose, mannose, and galactose alkynes including glycosyl rods were developed in good yields. The developed glycohybrids have been well characterized by various spectroscopic techniques, such as nuclear magnetic resonance, high-resolution mass spectrometry, and single-crystal X-ray data of L3. The protocol works well with the heteroaryl and naphthyl halides, and the mechanistic approach leads to CuI/ligand-assisted oxidative coupling. The coupling protocol has notable features, including low catalytic loading, cost-effectiveness, biocompatible nature, and a wide substrate scope. © 2023 American Chemical Society.