Lipase-Catalysed Biotransformations in Organic Synthesis

Stalker, Robert (1992) Lipase-Catalysed Biotransformations in Organic Synthesis. PhD thesis, University of Glasgow.

Abstract

In this thesis are described our investigations into the use of lipases as asymmetric catalysts in organic synthesis. The primary objective of this work was to achieve the resolution of pyrrolidine and piperidine alcohols via porcine pancreatic lipase catalysed transacetylations, using ethyl acetate as both the acyl donor and the solvent. Various synthetic routes directed towards the synthesis of these amino alcohols are described, along with our attempts at synthesising aziridine alcohols for use as enzyme substrates. Several experimental procedures were developed for the porcine pancreatic lipase mediated resolution of these amino alcohols, and acetylated products were obtained in enantiomeric excesses of between 0 and 57%. Also described in this thesis are our attempts to extend this work to the lipase-mediated resolution of alpha- and beta- amino acid derivatives. Herein is described the preparation and lipase-mediated alcoholysis of several 5(4H)-oxazolones ('azlactones') and 4,5-dihydro-1,3-oxazin-6-ones ('dihydrooxazinones'), using both porcine pancreatic lipase and Mucor miehei lipase. Low enantioselectivities were observed in these reactions. Finally, our investigation into the effect of varying the nature of the acyl donor in the lipase-catalysed acylation of (+/-)-2-octanol is described. No esterified products were obtained in the attempted coupling of simple carboxylic acids to the alcohol. The preparation of a number of 2,2,2-trichloroethyl esters of a number of simple alkyl, alkenyl and aromatic acids is described, and our investigation of the lipase catalysed reaction of these irreversible acyl donors with (+/-)-2-octanol is described. The monitoring of the progress of these reactions by gas chromatography is described. Results at variance with published results were obtained, and the implications of the results obtained are discussed.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1992
• Depositing User: Enlighten Team
• Unique ID: glathesis:1992-78397
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:29
• Last Modified: 30 Jan 2020 15:29
• URI: https://theses.gla.ac.uk/id/eprint/78397