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Title: A chemo-enzymatic approach to the synthesis of carbocyclic nucleosides and intermediates in the biosynthesis of carbocyclic nucleosides by Streptomyces citricolor
Author: Jackson, Ian D.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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The carbocyclic nucleosides aristeromycin I and neplanocin A II are produced from D-glucose by Streptomyces citricolor. (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 tert-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 Rhizopus arrhizus 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 Rhodococcus rhodochrous NCIMB 9703, to give the corresponding alcohol VIII suitable for further elaboration to carbocyclic nucleosides.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available