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
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.
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.