Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(Pseudohygrophorones). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of Manchester

1. Howard, Daniel. New Biocatalysts for Synthetically Useful Metabolites from Available Phenols.

Degree: 2019, University of Manchester

Toluene dioxygenase (TDO) is a Rieske type non-haem enzyme found within the soil bacteria, Pseudomonas putida (P. putida) and is responsible for catalysing the enantioselective cis-dihydroxylation of aromatic substrates. This remarkable trait of the TDO enzyme has enabled its application in the preparation of over 400 novel cis-diol bioproducts using whole cell biocatalysis. Recently, a new and synthetically useful bioproduct, (4S,5S)-4,5-dihydroxy-3-iodocyclohex-2-en-1-one, has been identified from the TDO catalysed biotransformation of 3-iodophenol. The purpose of this project was to demonstrate the synthetic application of this new bioproduct in the synthesis of natural product analogues, which possess anti-proliferative activity against different cancer cell lines. This was achieved by developing methodology towards a key enone building block, which was successfully applied in the synthesis of an analogue of the natural product incarviditone. Furthermore, a robust computational docking model was developed using the Goldâ„¢ software, which showed significant correlation between the predicted docking outcome and the experimentally observed results for a series of monocyclic substrates. The docking model was also used to rationalise the major and minor binding modes of the 3-iodophenol substrate in the TDO enzyme active site. The project also sought to develop an alternative synthetic methodology using butan-1,2-diacetal (BDA) protected (-)-quinic acid, which would provide the same stereochemical outcome as the newly discovered bioproduct. This was achieved despite considerable synthetic challenges encountered when trying to control the diastereoselectivity of a key conjugate addition reaction. The antipodal compounds of the natural product analogues obtained using the 3-iodophenol bioproduct and BDA protected (-)-quinic acid were also synthesised using acetonide protected (-)-quinic acid. By reacting the enantiomers of a key hydroxyenone intermediate obtained using the two pathways, a novel heterodimerisation was reported to afford an analogue of the natural product, incarvilleatone. Finally, all the biological activities of the synthesised natural product analogues were evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay: the results showed significant differences between the enantiomers of the incarviditone natural product analogues. Advisors/Committee Members: QUAYLE, PETER P, Whitehead, Roger, Quayle, Peter.

Subjects/Keywords: TDO; Dioxygenase; Toluene Dioxygenase; Quinic Acid; Incarvilleatone; Incarviditone; Biocatalysis; Iodo keto cis-diol; Iodo diol; P putida; Pseudomonas putida; P. putida UV4; COTC; Pseudohygrophorones

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Howard, D. (2019). New Biocatalysts for Synthetically Useful Metabolites from Available Phenols. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:318017

Chicago Manual of Style (16th Edition):

Howard, Daniel. “New Biocatalysts for Synthetically Useful Metabolites from Available Phenols.” 2019. Doctoral Dissertation, University of Manchester. Accessed July 07, 2020. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:318017.

MLA Handbook (7th Edition):

Howard, Daniel. “New Biocatalysts for Synthetically Useful Metabolites from Available Phenols.” 2019. Web. 07 Jul 2020.

Vancouver:

Howard D. New Biocatalysts for Synthetically Useful Metabolites from Available Phenols. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2020 Jul 07]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:318017.

Council of Science Editors:

Howard D. New Biocatalysts for Synthetically Useful Metabolites from Available Phenols. [Doctoral Dissertation]. University of Manchester; 2019. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:318017

2. Howard, Daniel. New biocatalysts for synthetically useful metabolites from available phenols.

Degree: PhD, 2018, University of Manchester

Toluene dioxygenase (TDO) is a Rieske type non-haem enzyme found within the soil bacteria, Pseudomonas putida (P. putida) and is responsible for catalysing the enantioselective cis-dihydroxylation of aromatic substrates. This remarkable trait of the TDO enzyme has enabled its application in the preparation of over 400 novel cis-diol bioproducts using whole cell biocatalysis. Recently, a new and synthetically useful bioproduct, (4S,5S)-4,5-dihydroxy-3-iodocyclohex-2-en-1-one, has been identified from the TDO catalysed biotransformation of 3-iodophenol. The purpose of this project was to demonstrate the synthetic application of this new bioproduct in the synthesis of natural product analogues, which possess anti-proliferative activity against different cancer cell lines. This was achieved by developing methodology towards a key enone building block, which was successfully applied in the synthesis of an analogue of the natural product incarviditone. Furthermore, a robust computational docking model was developed using the Goldâ„¢ software, which showed significant correlation between the predicted docking outcome and the experimentally observed results for a series of monocyclic substrates. The docking model was also used to rationalise the major and minor binding modes of the 3-iodophenol substrate in the TDO enzyme active site. The project also sought to develop an alternative synthetic methodology using butan-1,2-diacetal (BDA) protected (-)-quinic acid, which would provide the same stereochemical outcome as the newly discovered bioproduct. This was achieved despite considerable synthetic challenges encountered when trying to control the diastereoselectivity of a key conjugate addition reaction. The antipodal compounds of the natural product analogues obtained using the 3-iodophenol bioproduct and BDA protected (-)-quinic acid were also synthesised using acetonide protected (-)-quinic acid. By reacting the enantiomers of a key hydroxyenone intermediate obtained using the two pathways, a novel heterodimerisation was reported to afford an analogue of the natural product, incarvilleatone. Finally, all the biological activities of the synthesised natural product analogues were evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay: the results showed significant differences between the enantiomers of the incarviditone natural product analogues.

Subjects/Keywords: 540; P putida; Pseudohygrophorones; COTC; P. putida UV4; Pseudomonas putida; Iodo keto cis-diol; Iodo diol; Incarviditone; Incarvilleatone; Quinic Acid; Toluene Dioxygenase; Dioxygenase; TDO; Biocatalysis

…towards analogues of the natural products: incarviditone, incarvilleatone, pseudohygrophorones… 

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Howard, D. (2018). New biocatalysts for synthetically useful metabolites from available phenols. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/new-biocatalysts-for-synthetically-useful-metabolites-from-available-phenols(3b656275-726e-4843-9b31-2bc4e57c64dc).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771372

Chicago Manual of Style (16th Edition):

Howard, Daniel. “New biocatalysts for synthetically useful metabolites from available phenols.” 2018. Doctoral Dissertation, University of Manchester. Accessed July 07, 2020. https://www.research.manchester.ac.uk/portal/en/theses/new-biocatalysts-for-synthetically-useful-metabolites-from-available-phenols(3b656275-726e-4843-9b31-2bc4e57c64dc).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771372.

MLA Handbook (7th Edition):

Howard, Daniel. “New biocatalysts for synthetically useful metabolites from available phenols.” 2018. Web. 07 Jul 2020.

Vancouver:

Howard D. New biocatalysts for synthetically useful metabolites from available phenols. [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2020 Jul 07]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/new-biocatalysts-for-synthetically-useful-metabolites-from-available-phenols(3b656275-726e-4843-9b31-2bc4e57c64dc).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771372.

Council of Science Editors:

Howard D. New biocatalysts for synthetically useful metabolites from available phenols. [Doctoral Dissertation]. University of Manchester; 2018. Available from: https://www.research.manchester.ac.uk/portal/en/theses/new-biocatalysts-for-synthetically-useful-metabolites-from-available-phenols(3b656275-726e-4843-9b31-2bc4e57c64dc).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.771372

.