The aim of this project was to develop a synthetic strategy for the production of uncommon sugars thevetose (6-deoxy-3-O-methylglucose) and cymarose (2,6-dideoxy-3-O-methylallose or 2,6-dideoxy-3-O-methylaltrose) derivatives, present in the trisaccharide moiety of a pregnane glycoside with appetite-suppressant activity. A D-thevetose glycosyl donor was prepared from methyl D-glucopyranoside. The first step of the synthesis was the formation of a 4,6-O-benzylidene derivative that was selectively methylated on the 3-hydroxy group by using a copper mediated alkylation process. Treatment with NBS and reductive removal of the resultant bromide produced the required protected thevetose glycoside. This success is a vast improvement compared to the published results of the patent reporting this synthesis. Attempts to prepare the 2α-iodo derivative by direct nucleophilic substitution of a 2-O-triflate manno-derivative resulted in a most unusual rearrangement reaction. Allal derivatives as starting materials in the preparation of 2α-iodo sugars were also unsuccessful due to steric hindrance provided by the axial 3-methoxy group. Preparation of a cymaroside precursor was achieved by using glucal as a starting material and by the inversion of C-3 in a consecutive oxidation/reduction sequence of the iodo acetate. Lastly, the preparation of the β-oleandroside derivative of cholesterol was achieved in a model reaction. The sugar oleandrose is a C-3 epimer to cymarose and it can be found in pregnane and cardenolide glycosides. / Professor F.R. van Heerden
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:2823 |
| Date | 13 June 2008 |
| Creators | Jacobs, Buyiswa Getrude |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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