Mupirocins F and H are metabolites isolated from cultures of mutant strains of Pseudomonas f1uorescens. Synthetic routes have been developed to these compounds to confirm their structures Investigations into the synthesis of 22 led to two novel rearrangement products 48 and 55 and their structures were confirmed through extensive spectroscopic studies. Methyl mupirocin F was prepared in two steps from pseudomonic acid A via methylation with TMS- diazomethane to give methyl pseudomonate 3 followed by a selective TEMPO oxidation to yield methyl mupirocin F 22. The total synthesis of mupirocin H 73 has been achieved using a flexible synthetic strategy. Lactone 85 was prepared from bicycloheptanone 88 which on alkylation with 86 gave 186 with complete stereocontrol and all six asymmetric centres intact. Reductive cleavage of lactone 186 via the intermediate dithiane 199 installed the required methyl group and oxidation gave 206. Removal of the protecting groups gave mupirocin H 73.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:558095 |
| Date | January 2011 |
| Creators | Scott, Robert W. |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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