The use of Mitomycin C in the treatment of a wide range of neoplastic conditions is discussed. The mechanism of action of mitomycin anticancer antibiotics under reductive activation conditions using either enzymes, sodium dithionite, catalytic hydrogenation or chromium (Il) perchlorate is examined, as is the alkylation of DNA. An intramolecular [3+2] cycloaddition strategy has been employed to synthesise the pyrrolo[I,2-aJ]indole nucleus for a wide range of cyclopropamitosenes, whereas the key step in the synthesis of pyrrolo[I ,2-a]indoles without the cyclopropane ring was a modified Wittig reaction. From the onset of the work it was important to investigate the role of the 7 -methoxy group. Hence a variety of cyclopropamitosenes or related pyrrolo[I,2-a]indoles were subjected to C-7 exchange reactions with either (i) other alkoxides or (ii) cyclic / acyclic amines. In this way, structural modification at C-7 can be related to the biological results. Biological and electrochemical data were recorded for the cyclopropamitosenes and related pyrrolo[I,2-a]indoles and correlated with their structures.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:241110 |
| Date | January 1992 |
| Creators | O'Sullivan, Noeleen |
| Publisher | Loughborough University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://dspace.lboro.ac.uk/2134/14132 |
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