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Title: Towards the total synthesis of a potential M1 muscarinic agonist and study on regioselective cyclisations for the synthesis of highly substituted piperazinones
Author: De Francesco, Laura
ISNI:       0000 0004 2749 6149
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2006
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The preparation of piperazinones, which are important pharmacophores, is reviewed in the introduction. This thesis provides an elucidation of the cyclisation mechanisms involving chiral secondary 1,2-diamines both with haloacetates and with 1,2-dicarbonyl compounds. The work on selective cyclisations consists of mainly three parts: (i) Regioselective preparation of N.W-disubstituted 5- and 6-piperazinones with elucidation of the cyclisation mechanism using D2O and C label (ii) Regioselective preparation of W-dibenzyl 3,6- and 3,5-disubstituted piperazinones using methyl a-bromophenylacetate, methyl 2-bromopropionate, methylglyoxal, phenylglyoxal and benzil (iii) Selective preparation of N-acetates of 5-substituted piperazinones by hydrogenolysis and intramolecular cyclisation in the same reaction pot starting from substituted dibenzyl 1,2-diaminoacetates. Additionally, the total synthesis of a potential Mi muscarinic agonist for treatment of Alzheimer's disease was planned and almost completely carried out. The multistep sequence presented two challenging steps: regioselective preparation of a chiral piperazinone successfully achieved with the haloacetate cyclisation described above Birch reduction of a lactam to an aminol, in presence of an amide, which acts as a nucleophile and cyclises to give a 1,1-aminoamide.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available