Abstract
M.Sc. (Chemistry)
The aim of this study was to investigate alternative routes for the stereocontrolled
synthesis of hydroxylated indolizidine, piperidine and pyrrolidine alkaloids, starting from
monosaccharides as chiral building blocks. This study was not aimed at improving
consisting routes - it was rather aimed at developing new routes towards the synthesis
of these alkaloids. Mixed results were obtained in the investigation into alternative routes
for the synthesis of the bicyclic poly hydroxylated indolizidine alkaloids, but a new and
efficient stereospecific synthesis of polyhydroxylated piperidine- and pyrrolidine alkaloids
were developed.
The aims and results can be summarised in more detail as follows:
a. Stereospecific synthesis of castanospermine. The synthesis of this medium sized
nitrogen-containing bicyclic molecule was approached in a unique way. The utilization
of bifunctional Wittig- and Wittig-Horner reagents containing nitrogen functionalities was
considered promising for the aims of this study. By the usage of known reactions, e.g.
Wittig, Wittig-Horner, Schiff-base and Aza-Wittig reactions, it was foreseen that these
bifunctional reagents could be coupled in two concurrent steps to dicarbonyl compounds
to form a nitrogen containing rings. Several nitrogen containing Wittig reagents were
prepared. At the one end of these reagents a phosphonate or phosphine group furnished
the phosphorus moiety while the other end of these reagents comprised the nitrogen
moiety by reduction of a nitrile group or azide displacement of a leaving group.
No coupling was obtained between these bifunctional reagents and a dicarbonyl
compound derived from D-glucose and the influence of two functional groups in such
close proximity in the Wittig reagent is being further investigated. Coupling was,
however, achieved by the utilization of an alternative bifunctional reagent in which a
Wittig-Horner reaction was used. The successful implementation of this unique
methodology in the synthesis of medium size nitrogen containing ring is being further
investigated.