Please use this identifier to cite or link to this item: http://localhost:8081/xmlui/handle/123456789/14572
Authors: Kumar, Manoj
Keywords: Discovery About Two Decades Ago;Multicomponent Reactions;Generated enone;Provided Access
Issue Date: Jun-2015
Publisher: Dept. of Chemistry Engineering iit Roorkee
Abstract: From its discovery about two decades ago, multicomponent reactions based on [4+1] cycloaddition of in situ generated enone to isocyanides have remained a rich sources of structural diversity and have provided access to a large numbers of functionalized furanones and related scaffolds. Many of these products are biological relevant and show a wide range of biological activities which will be discussed in each successive chapters. From mechanistic perspective, this class of reactions is similar to other [4+1] cycloaddition based MCRs such as GBB reaction and possesses a unique combination of simplicity, efficiency and diversity. Unfortunately, the survey of the preceding literature revealed the potential of this seemingly important multicomponent reaction is not yet fully explored. The present thesis is an attempt to fill this void and to broaden the scope and reach of this unique MCR. The whole thesis is divided into five chapters. First chapter is an introductory chapter, which defines the background of the research work, problem statement and objective. This chapter covers the literature on multicomponent reaction especially of IMCRs and their role in drug discovery and a brief history of [4+1] cycloaddition based multicomponent reactions. Chapter-2 details synthetic improvement towards biologically important functionalized dihydrobenzofurans. Previously, this reaction was limited to only two aldehydes (4- nitrobenzaldehyde and glyoxals). In order to improve the scope of the reaction, a large number of conditions from simple grinding to microwave heating were surveyed. Eventually, a microwave assisted solvent and catalyst free protocol has been devised, which was found suitable to a wide range of aldehydes. Chapter-3 entails the synthesis of structurally different benzo[f]furo[3,2-c]chromen-4-(5H)- ones and furo[3,2-c]quinolin-4-(5H)-ones. For this purpose, two new C-H acids, 1-hydroxy- 3H-benzo[f]chromen-3-one and 4-hydroxyquinolin-2(1H)-one were introduced for the first time in this MCRs. The potential and scope of this reaction was demonstrated by synthesizing a diverse array of annulated furans. Chapter-4 reports the use of vinyl esters as effective acetaldehyde surrogate in this transformation. This kind of surrogacy is important in the cases where aliphatic aldehydes (such as acetaldehyde) do not perform well (as in our case). A number of methyl substituted functionalised furans have been constructed using different types of C-H acids. Use of vinyl Abstract of the thesis esters as effective acylating agent for transesterification of wide range of phenols was also investigated. Chapter-5 includes the results of extensive computational docking of synthesized and reported furanones against Pf-DHFR. All the compounds were ranked according to their binding energy and drug/lead likeness. The important interaction between pathogen protein and fused furanones were analyzed in detail. Two candidates furochromenones 3- (naphthalen-2-yl)-2-(phenylamino)-4H-benzo[f]furo[3,2-c]chromen-4-one (N4q) and 3- (benzo[d][1,3]dioxol-5-yl)-2-(phenylamino)-4H-benzo[f]furo[3,2-c]chromen-4-one (N4o) had shown highest binding affinity with acceptable drug likeness and hence could be considered as a good starting points for further exploration.
Research Supervisor/ Guide: Sharma, Anuj
Gupta, V. K.
metadata.dc.type: Thesis
Appears in Collections:DOCTORAL THESES (chemistry)

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