The carbocyclic nucleosides aristeromycin I and neplanocin A II are produced from D-glucose by <i>Streptomyces citricolor</i>. (Fig. 8570A) To investigate the mechanism of the biosynthesis, an effective route to a putative intermediate III has been developed. By modifications to a known procedure, a single low yielding and unreliable reaction has been improved considerably. (Fig. 8570B) By using a <i>tert-</i>butyl-diphenyl silyl group in place of the acetyl group present in the original procedure, a more stable compound was obtained, which was tolerant to the insertion of a protected hydroxy methyl moiety. Yields for this reaction were increased from £ 20% to 76%. An efficient route to enantiomerically pure 3-benzyloxymethylcyclopentene VI has been demonstrated. Using <i>Rhizopus arrhizus</i> ATCC 11145, ethylcyclopentanone-2-carboxylate was reduced to give a single enantiomer of 2-hydroxy-cyclopentanecarboxylic acid ethyl ester VII which was converted in 5 steps to the desired substrate. (Fig. 8570C) It was observed that VI could be hydroxylated at C-5 by incubation with <i>Rhodococcus rhodochrous </i>NCIMB 9703, to give the corresponding alcohol VIII suitable for further elaboration to carbocyclic nucleosides.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652890 |
| Date | January 2003 |
| Creators | Jackson, Ian D. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15092 |
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