Aristeromycin 4 and neplanocin A 5 are biologically active carbocyclic nucleosides produced by the organism <i>Streptomyces citricolor</i>. Previous studies towards elucidating their biosynthesis have led to a proposed biosynthetic pathway in which D-glucose is converted <i>via</i> a number of carbocyclic intermediates to neplanocin A and aristeromycin. This thesis describes the studies that have been carried out in order to: i. identify the first formed carbocyclic intermediate on the biosynthetic pathway (Chapter 2). ii. determine the identity of the phosphorylated intermediates prior to neplanocin A (Chapter 3). The novel (2<i>R</i>, 3<i>S</i>, 4<i>R</i>) and (2<i>R</i>, 3<i>S</i>, 4<i>S</i>) keto-tetrols 95, <i>ent-</i>95 and 116 have been prepared and their syntheses are described. To determine whether those intermediates lie on the biosynthetic pathway, feeding studies have been carried out using a mutant of <i>Streptomyces citricolor</i>. The results of these studies, described within, suggest that both the (2<i>R</i>, 3<i>S</i>, 4<i>R</i>) keto-tetrol 95 and its diastereomer (2<i>R</i>, 3<i>S</i>, 4<i>S</i>) keto-tetrol 116 lie on the biosynthetic pathway. The syntheses of the known intermediate tetrol 83a, the proposed phosphorylated intermediate 5-phosphate 83b and the corresponding 1-phosphate 152, <i>via</i> multi-step syntheses from the cyclopentenone 61, prepared from either D-ribose 126 or cyclopentadiene 36, are described.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:660397 |
| Date | January 2000 |
| Creators | Paterson, Nicola Margaret |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/11236 |
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