Stereochemical and Mechanistic Studies in Biosynthetic Model Systems

Matassa, Victor Giulio (1978) Stereochemical and Mechanistic Studies in Biosynthetic Model Systems. PhD thesis, University of Glasgow.

Abstract

The in vivo isomerisation of isopentenyl pyrophosphate to dimethylallyl pyrophosphate, and the condensation of these two C-5 units, giving geranyl pyrophosphate, although formally recognisable as processes, have been explained by different mechanisms, mainly because the stereochemistries of the in vivo transformations are different. The stereochemical preference of the SE' reaction, in vitro, unlike the much-studied process, has received little attention; only one conscious effort has been made to clarify the issue: a syn preference was noted for this non-enzymatic SE' reaction, in direct contrast with theoretical predictions. PART I: In this Thesis, the design of model systems capable of investigating the SE' reaction, and synthetic approaches to these models, are described. The basic concept used was that of effecting SE' cyclisation of a suitably functionalised bicyclo(3.3.1)nonane - a "seco-adamantane" - to an adamantane nucleus. Several approaches to the first of these molecules, (29), were probed, and one, involving a Wittig reaction on lactol (105), furnished the required molecular skeleton (113), Z-olefin;. the isomeric E-olefin (137) was then accessible by an olefin inversion sequence. However, in a series of experiments, it was established that aldehyde epimerisation had occurred during the Wittig reaction; these experiments uncovered some interesting chemistry, including a novel ring-closure to the oxaadamantane (129). A second model, (155), was investigated, and considerable progress made towards it; but, spectral data (of enol (159)) suggested that an epimerisation had occurred in this route also. Experimental difficulties with a third model,(173), resulted in modification to the closely-related benz-bicyclo(3.3.2)decane (192). Work towards this target molecule has progressed to the penultimate stage, (186). PART II: The models of Part I required specific isotopic labelling with deuterium (e.g. in (29), H or H' = D) for successful investigation of the SE' reaction; in particular, a specifically 2-deuteriated n-propyl iodide was required. Starting from (S)-(-)-ethyl lactate (13), routes to (R)-n-propyl-2-2H tosylate (43) and (R)-n-propyl-1,1,2-tosylate (45) have been achieved. Methods for differentiating the enantiotopic protons on C-2 of n-propanol (and hence for determining accurately the optical purities of (43) and (45)) by 1H. m. r. spectroscopy have been investigated.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1978
• Depositing User: Enlighten Team
• Unique ID: glathesis:1978-78784
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 14:54
• Last Modified: 30 Jan 2020 14:54
• URI: https://theses.gla.ac.uk/id/eprint/78784