Sophie Manner
Studierektor
Design, synthesis and evaluation of spiro-bicyclo[2.2.2]octane derivatives as paclitaxel mimetics
Författare
Summary, in English
The primary intention with the work presented in this thesis was to design and synthesize paclitaxel mimetics, based on a rigid skeleton decorated with the groups important for the paclitaxel activity. Molecular modelling was used to identify a spiro-bicyclo[2.2.2]octane skeleton as a suitable substitute for the rigid paclitaxel core. Four different paclitaxel mimetics have successfully been synthesized and tested for their biological activity in five breast-derived cell lines. In addition, some intermediates were also included in the biological evaluation. Some of the compounds tested were shown to be toxic but were less active than paclitaxel itself. In addition, methodology for the synthesis of bridgehead substituted bicyclo[2.2.2]octane-2,6-diones were developed followed by evaluation of the products as substrates in the asymmetric baker’s yeast reduction.
Avdelning/ar
- Centrum för analys och syntes
Publiceringsår
2008
Språk
Engelska
Fulltext
Dokumenttyp
Doktorsavhandling
Ämne
- Organic Chemistry
Nyckelord
- asymmetric baker's yeast reduction
- paclitaxel
- spiro
- bicyclo[2.2.2]octane
- paclitaxel mimetics
Status
Published
Handledare
- Torbjörn Frejd
ISBN/ISSN/Övrigt
- ISBN: 978-91-7422-202-9
Försvarsdatum
12 september 2008
Försvarstid
09:30
Försvarsplats
Kemicentrum sal K:B
Opponent
- Christina Moberg (Professor)