The f)-lactam or azetidinone 4-membered heterocyclic nng system has been synthesised by many different synthetic strategies and these are well documented in the literature. Many of these strategies give substituted azetidinone rings displaying defined stereochemistry which are used as the building block for many modern day antibiotics. It was therefore intended to pursue a method of azetidinone ring formation using cheap and readily available starting materials employing a [2+2] cycloaddition reaction which, according to the literature, had only a few examples and was seen to be an area ripe for research. Taking urethane in anhydrous THF and metalating with n-butyl lithium, followed by the subsequent addition of phenyl vinyl sulfone, it was envisaged that the two would react in such a way to give the -l-membered azetidinone ring. It was found however that the carbon-nitrogen bond was formed but subsequent cyclisation did not follow and therefore no azetidinone was formed. Although azetidinone ring was not detected the novel compound N,N-bis-(phenylsulfonylethyl) urethane was isolated. This compound was of interest since it was hoped that it could provide a new route to substituted pyridines. Various methods were undertaken in an attempt to cyclise this molecule via the generation of a-sulfonyl carbanions and reactions with a variety of electrophiles. During our experiments no cyclised products were detected. TIle replacement of phenyl sulfonyl group with triphenylphosphonium bromide provided a new hope for azetidinone synthesis since its ability to stabilise a-sulfonyl carbanions and promote reaction with electrophiles was well established. Experiments of this nature failed to produce an azetidinone. TIle next stage of research was to investigate a new route to the production of quinolone antibiotics. Quinolones, particularly those which are furnished with a fluorine at C-6 position, are the new generation of antibiotics which exhibit a high activity and selectivity towards pathogens which have become resistant to older antibiotics such as penicillin. Needless to say their importance in the pharmaceutical industry has increased dramatically over recent years and research into the improvement of synthetic strategies towards the total synthesis of these molecules has attracted much commercial interest. Meth-Cohn showed that quinolones can be formed in excellent yield by the reaction of N-alkylformanilides in phosphorus oxychloride and activated acid chlorides e.g. methyl malonyl chloride. This approach is examined regarding the synthesis of both novel and known quinolone antibiotics (norfloxacin and ciprofloxacin). Work on this topic has produced encouraging results with the synthesis of important antibacterial intermediates.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:242127 |
| Date | January 1997 |
| Creators | Jackson, Andrew Edward |
| Publisher | University of Sunderland |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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