Σύνθεση και μελέτη δομής ινδολικών παραγώγων με πιθανή βιολογική δράση

Abstract

The present thesis is divided into three parts. The first part is devoted to the introduction, whereas the second part to the results-discussion session. The last part describes the experimental procedures that have been followed. The introductory part consists of six chapters. The first chapter is referred to the indole ring, the reactions in which the ring takes part and to the indole alkaloids due to their significant pharmacological activity. In the next two chapters reference is made to the nucleophilic addition reactions of indolopyranones and pyranones in general, and to Diels-Alder reactions. Moreover, particular attention is given to β-carbolines, since these compounds are formed from a large number of reactions studied in this thesis. The fourth chapter refers to reactions of isocyanates with compounds containing double bond and to reactions assisted by microwave radiation, whereas the fifth chapter studies the chemistry of isocyanides giving special attention to tosylmethyl isocyanide (TosMIC). The last chapter outlines the importance of the multi-component reactions (MCRs) with particular reference to the Ugi and Passerini reactions. The second part covers the results of this thesis and consists of five chapters. The first chapter describes the preparation of a series of indolopyranones (47a,c,e,i,l,m) used as raw materials in the following three chapters. The next three chapters describe the nucleophilic addition reactions of indolopyranones with nucleophiles and ambident nucleophiles and Diels-Alder reactions of indolopyranones with isocyanates. In all nucleophilic addition reactions the nucleophilic attack takes place into one of the two electrophilic centers of indolopyranones. This attack depends on several factors, such as the nucleophiles strength, the solvent, the reaction temperature and steric hindrance. The products isolated from the above reactions are indole-3-acetamides 245a-f, 246a-c, 249a-c, 328a-b and 340a-d, β-carbolinones 265a-f, 266a-f, 285a-b, 300a-d, 301a-b and 339a-c, diazepinoindolones 250a-f, 284a-h and 286, indolylacetohydrazide 264a-c, the pentacyclic compound 327a-c and a novel class of compounds, the pentacyclic indolepyridobenzimidazoles 313a-e and 314a-d. The Diels-Alder reactions with isocyanates were carried out using microwave radiation and β-carbolinones 349a-h were formed. The fifth chapter refers to multi-component reactions involving 2-substituted indolylacetic acids 385a-b, and to their preparation from the corresponding indolopyranones 47c,i. Ugi and Passerini reactions and a series of multi-component reactions, where the action of indolylacetic acid 385b was catalytic, were undertaken. The products isolated from the above reactions are Ugi products 386a-c, Passerini products 396a-b and N-(tosylmethyl)acetamides 407a-h. In the last part detailed analysis of the experimental conditions is made. All spectral data for each compound described in results-discussion session is given. The structure of novel compounds was assigned with ΗR, NMR (1H, 13C, COSY H-H and C-H, NOESY H-H and COLOC C-H), MS and elemental analyses data.