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Title: Synthesis and design of isatogens of potential biological interest
Author: Swain, C. J.
Awarding Body: Sunderland Polytechnic
Current Institution: University of Sunderland
Date of Award: 1980
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The synthesis, including the preparation of the intennediate acetylenes, indolines and benzoin oximes, the reactions and biological properties of isatogens are critically reviewed. A detailed study is made of the preparation of 2-substituted indolines, from indoles, and 2-substituted-I-hydroxyindoles, from benzoin derivatives, and their subsequent oxidation to isatogens with 3-chloroperbenzoic acid. In particular the mechanisms, limitations and scope of these methods have been investigated. The most versatile method for the synthesis of isatogens is confinned as that proceeding via the intermediate tolans. The preparation of a variety of terminal acetylenes is described, in particular 2-,3-, and 4-ethynylpyridines are prepared in higher yields than previously reported. The acetylenes were coupled with a variety of 2-nitrohalogenoaryl compounds using bis(triphenylphosphine) palladium(II) chloride to give a variety of novel tolans including those derived from ethynylphenylsulphide. The steric and electronic limitations of these reactions are discussed. Cyclisation of the tolans gave a variety of novel isatogens including 2-phenyl and 2-pyridyl, 4, 5, 6, and 7- substituted, isatogens and a number of 2-thiophenylisatogens. The latter are the first isatogens to be described with a heteroatom at the 2-position. The analogous reaction with phenoxyacetylene failed to yield the isatogen. The importance of steric and electronic factors and scope of all these reactions is discussed. 1 13 The mass spectra, Hand C nmr spectra are discussed for a number of indolines and isatogens. An interesting upfield shift of the 3-methyl signal in 2,3 trans di- and 3,3,3-trimethylindoline tosylates is described. The activity of the isatogens in three different biological systems, a) ATP antagonism, b) muscle relaxation, and c) inhibition of mitochondrial respiration is described and a preliminary attempt is made to relate activity with a variety of physico-chemical parameters; new isatogens, with novel structures, are proposed which would be predicted to be more potent and more selective in their biological actions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chemistry, general Chemistry