Abstract
Ph.D. (Chemistry)
The aim of this study was the development of stereoselective routes for the asymmetric synthesis
of chiral precursors of I1-deoxy-1l-thiaprostaglandins and albomysin di, using carbohydrates
as chiral building blocks. A brief overview of known stereocontrolled routes for
the synthesis of sulphur-containing monosaccharides and heterocyclic prostaglandin
analogues is presented.
Approaches to the stereocontrolled synthesis of I1-deoxy-11-thiaprostaglandins from Larabinose
are described. Special topics in this part of the study include approaches to the
preparation of chiral tetrahydrothiophenes. The 1,4-diol 5-0-benzoyl-3-deoxy-3-C-(carboxymethyl-
2,3-y-lactone)-L-lyxitol (146a), was identified as a possible chiral building block
for the proposed route towards 11-thiaprostaglandins. New groups for the activation of the
hydroxyl functions of the 1,4-diol in order to introduce the ring sulphur atom via a 1thiobenzyl
ether, were investigated. The l,4-diol was subsequently transformed into a 1,4dimesylate
and this compound proved to be the most suitable for the generation of the
tetrahydrothiophene unit. This investigation resulted in an efficient synthesis of 11thiaprostaglandin
precursors using glucose as a chiral building block.
In the second part of the investigation, approaches to the stereoselective synthesis of a
potential precursor for the synthesis of albomysin dr are described.
An investigation of the selective acylation of acyclic pentoses are also presented. The aim
of this study was the regioselective introduction of a leaving group, for example a tosylate,
in acyclic derivatives of pentose without protecting any of the secondary hydroxyl groups.
This strategy would make intramolecular cyclisations possible with a suitable nycleophile
present on C-l. Some of the compounds in the pentose series investigated, furnished
dibutyltin complexes which were regioselectively acylated in an efficient manner.
Starting from L-arabinose an alternative strategy for the synthesis of a precursor for the synthesis
of aIbomysin di is also given. The synthesis involved the preparation of 1-0-acetyl2,3,
5-tri-O-benzoyl-4-thio-xylofuranose, followed by conversion to the required nucleoside.