Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Biotransformations with yeasts and their applications in organic synthesis.

Tools
- Tools
+ Tools

Christen, Markus (1988) Biotransformations with yeasts and their applications in organic synthesis. PhD thesis, University of Warwick.

[img]
Preview
PDF
WRAP_Theses_Christen_2016.pdf - Submitted Version - Requires a PDF viewer.

Download (4Mb) | Preview
Official URL: http://webcat.warwick.ac.uk/record=b3064474~S15

Request Changes to record.

Abstract

This thesis describes the synthesis of a new chiral synthon via biotransformation and the applications of this chiron in organic synthesis.

It was possible to reduce a variety of β-ketoesters with a range of yeast species to the corresponding β -hydroxyesters. We selected from these screening results methyl 4-(p-chlorophenylthio)-3-oxobutanoate as the substrate of choice and the two yeast strains Saccharomyces cerevisiae and Candida guilliermondii as the biocatalysts. Immobilisation of the yeasts proved to be a successful method for improving the yield and enantiomeric excess in the biotransformation, and we obtained the product methyl 4-(p-chlorophenylthio)-3-hydroxybutanoate in both enantiomeric forms, depending on the choice of the biocatalyst. S.cerevisiae, immobilised on alginate, gave the L-product in 60% yield and 80% ee, whilst C.guilliermondii afforded the D-product in 60% yield and 87% ee. Both enantiomers could be recrystallised to an optical purity of ee > 95%.

We then proceeded to explore the reactivity pattern of our new chiron. We found that it was possible to protect the hydroxyl group with a variety of protecting groups under acid or base catalysed reaction conditions. We chose the tert-butyldimethylsilyl group as the most suitable one for our purposes. Hydrolysis of the protected ester, followed by conversion into the imidazolide and treatment with methyl magnesium malonate resulted in the formation of a new β-ketoester, which in turn could be deprotected with an overall yield of 68% to methyl 4-(p-chorophenylthio)-5-hydroxy-3-oxohexanoate. This ester was subsequently reduced with tetramethylammonium triacetoxyborohydride to the anti diastereomer and with methoxydiethylborane / sodium borohydride to the syn diastereomer. We succeeded therefore in synthesizing all four stereoisomers of methyl 6-(p-chlorophenylthio)-3,5-dihydroxyhexanoate in enantiomerically pure form.

Additionally we found that it was possible to chlorinate the original β-hydroxyester at C-4 under radical reaction conditions. This allowed us to form a new carbon-carbon bond by treatment of the chlorinated product with a silylenolether under Lewis acid catalysis. Further manipulation of this addition product allowed the synthesis of 3-hydroxytetradecanoic acid with high enantiomeric excess. The alkylation at C-2 was easily achieved via the corresponding dioxanone by deprotonation and diastereoselective methylation.

Item Type: Thesis or Dissertation (PhD)
Subjects: Q Science > QD Chemistry
Library of Congress Subject Headings (LCSH): Organic compounds -- Synthesis -- Research, Biotransformation (Metabolism), Yeast fungi -- Biotechnology
Official Date: September 1988
Dates:
DateEvent
September 1988Submitted
Institution: University of Warwick
Theses Department: Department of Chemistry
Thesis Type: PhD
Publication Status: Unpublished
Supervisor(s)/Advisor: Crout, David
Sponsors: GlaxoSmithKline
Format of File: pdf
Extent: 181 pages : illustrations, charts
Language: eng

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us