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New methodology for the synthesis of chiral pyrrolidine derivatives from monosaccharides

M.Sc. (Chemistry) / The aim of this study waa to develop new methodology for the synthesis of chiral pyrrolidine derivatives Crom monosaccharides. An overview of the stereoselectlve synthesis of pyrrolldlnes as precursors of natural compounds 11 given, as well as a summary ,of their uses in the synthesis of two groups of biologically active natural compounds and their analogues. A synthetic approach towards a pyrrolidine synthon for an was investigated by means of stereoselective and stereospecific reactions. The ability to incorporate an N-O linkage into the synthon to allow the synthesis of a true isosteric analogue of PG F2Q , namely ll-a:a-ll-hydroxy-PG F2Q, Is a challenge that has not yet been accomplished. (IR,5R,6S)~benzoyloxymethyl-7-beI1%yloxy-3-oxo-7-aza-2-oxa-bicyclo[3.3.0]octane (162) was synthesized Cram L-arabinose. The nitrogen atom was introduced at e-l by the reaction of the furanose (140) ~itlt G-beiU.ilL1JlIJA1:4Jilllle h'ydl~hluride to Iuraish an oxime ether. Mesylatlon and subsequent reduction of the oxime double bond enabled cyclisatlon to the pyrrolidine synthon. This desired N-O linkage was thus maintained. Problems with the removal of the oxime protecting group were envisioned and, in order to overcome them, oxime ethers were synthesized Crom various hydroxylamine salts. However, some oxime ethers then cyclised to afford the I-hydroxylamino furanoses. A balance between a hogh yield of the required acyclic oxime Isomers and the easy removal of the protecting groups has yet to be achieved. Those protecting groups that allowed formation of the oxime in high yields proved difficult to remove at a later stage of the synthesis and further studies into the suitability of the various protecting groups are currently being carried out.
Date14 April 2014
CreatorsBraithwaite, Dana Helen
Source SetsSouth African National ETD Portal
Detected LanguageEnglish
RightsUniversity of Johannesburg

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