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 +publisher:"Dalhousie University" +contributor:("Dr. David L. Jakeman"). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Dalhousie University

1. Beaton, Stephen A. Evaluation and Synthesis of Sugar 1-Phosphate Substrates for Nucleotidylyltransferases.

Degree: MS, Department of Chemistry, 2010, Dalhousie University

The study of many of glycosyltransferases is limited due to an inadequate access to sugar nucleotides. Preparation of sugar nucleotides through the use of nucleotidylyltransferases with broad substrate specificities is gaining significant interest and offers high yields and stereospecificity. Physiologically, the glucose 1-phosphate thymidylyltransferase catalyzes the condensation of ?-D-glucose 1-phosphate and deoxythymidine triphosphate to yield deoxythymidine diphospho glucose. Exploiting and targeting these enzymes also has the potential of yielding new therapeutics. Cps2L is a thymidylyltransferase isolated from Streptococcus pneumoniae, with broad substrate flexibility. The substrate specificity of Cps2L was evaluated with new sugar 1-phosphate analogues to gain further insight into substrate and inhibitor requirements. Several sugar 1-phosphate analogues including sugar 1C-phosphonates (and analogues thereof), 2-deoxy-2-fluorosugar 1-phosphates, and glucopyranose 1- boranophosphates have been used to probe the sugar 1-phosphate modification tolerance of Cps2L. In addition, NMR spectroscopy was used to determine the anomeric stereochemistry of 2-deoxy-2-fluorosugars nucleotide products. For those substrates that were accepted by Cps2L, steady-state kinetic parameters were determined. The enzyme is able to almost equally form Michaelis complexes with different sugar substrates, whereas the turnover values for obtaining the corresponding sugar nucleotide were different. The evaluation of the substrate tolerance of Cps2L, as well as the synthesis of ?-D-glucose-1C-thiophosphonate, a difluoro and a bisphosphono analogue of ?-D-glucose 1C-phosphonate will be described. Advisors/Committee Members: N/A (external-examiner), Dr. R.L. White (graduate-coordinator), Dr. S.L. Bearne, Dr. N.D. Schepp, Dr. T.B. Grindley (thesis-reader), Dr David L. Jakeman (thesis-supervisor), Not Applicable (ethics-approval), Yes (manuscripts), Yes (copyright-release).

Subjects/Keywords: Nucleotidylyltransferases; organic synthesis; enzymes; sugar nucleotides

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Beaton, S. A. (2010). Evaluation and Synthesis of Sugar 1-Phosphate Substrates for Nucleotidylyltransferases. (Masters Thesis). Dalhousie University. Retrieved from http://hdl.handle.net/10222/12815

Chicago Manual of Style (16th Edition):

Beaton, Stephen A. “Evaluation and Synthesis of Sugar 1-Phosphate Substrates for Nucleotidylyltransferases.” 2010. Masters Thesis, Dalhousie University. Accessed May 29, 2020. http://hdl.handle.net/10222/12815.

MLA Handbook (7th Edition):

Beaton, Stephen A. “Evaluation and Synthesis of Sugar 1-Phosphate Substrates for Nucleotidylyltransferases.” 2010. Web. 29 May 2020.

Vancouver:

Beaton SA. Evaluation and Synthesis of Sugar 1-Phosphate Substrates for Nucleotidylyltransferases. [Internet] [Masters thesis]. Dalhousie University; 2010. [cited 2020 May 29]. Available from: http://hdl.handle.net/10222/12815.

Council of Science Editors:

Beaton SA. Evaluation and Synthesis of Sugar 1-Phosphate Substrates for Nucleotidylyltransferases. [Masters Thesis]. Dalhousie University; 2010. Available from: http://hdl.handle.net/10222/12815


Dalhousie University

2. Martinez-Farina, Camilo. Investigations into the Biosynthesis, Derivatization, and Purification of Jadomycins.

Degree: MS, Department of Chemistry, 2015, Dalhousie University

Nature produces many clinically used medicines in the form of natural products. These compounds can be isolated from a variety of sources, but bacteria have been shown to be the most prolific source. The strain Streptomyces has been thoroughly investigated for such natural products, with Streptomyces venezuelae ISP5230 showing the ability to produce the clinically used antibiotic chloramphenicol, as well as the jadomycins, a family of secondary metabolites. These secondary metabolites are produced through a biosynthetic pathway where the incorporation of the amino acid into the jadomycin structure is likely non-enzymatic. This allows for jadomycins to be readily derivatized, where upwards of twenty-five derivatives have been previously isolated. This work presents the amplification of the jadomycin library through the production of novel jadomycins, as well as their further diversification through the use of synthetic derivatization. The study of jadomycins is not only important chemically, but also biologically because they have been shown to possess anti-cancerous properties. For this reason, the two synthetic derivatives were assessed for biological activities and their results are discussed herein. Investigations were also carried out to develop a method to assess biological activity by nuclear magnetic resonance, and are presented. Finally, investigations into the jadomycin purification methodology were carried out using JadX, a potential regulatory protein in the jadomycin biosynthesis, and are discussed. Advisors/Committee Members: n/a (external-examiner), Dr. Mark Stradiotto (graduate-coordinator), Dr. T. Bruce Grindley (thesis-reader), Dr. Frances L. Cozens (thesis-reader), Dr. David L. Jakeman (thesis-supervisor), Not Applicable (ethics-approval), Yes (manuscripts), Yes (copyright-release).

Subjects/Keywords: Natural Products; Jadomycin; Precursor-Directed Biosynthesis; WaterLOGSY

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Martinez-Farina, C. (2015). Investigations into the Biosynthesis, Derivatization, and Purification of Jadomycins. (Masters Thesis). Dalhousie University. Retrieved from http://hdl.handle.net/10222/56323

Chicago Manual of Style (16th Edition):

Martinez-Farina, Camilo. “Investigations into the Biosynthesis, Derivatization, and Purification of Jadomycins.” 2015. Masters Thesis, Dalhousie University. Accessed May 29, 2020. http://hdl.handle.net/10222/56323.

MLA Handbook (7th Edition):

Martinez-Farina, Camilo. “Investigations into the Biosynthesis, Derivatization, and Purification of Jadomycins.” 2015. Web. 29 May 2020.

Vancouver:

Martinez-Farina C. Investigations into the Biosynthesis, Derivatization, and Purification of Jadomycins. [Internet] [Masters thesis]. Dalhousie University; 2015. [cited 2020 May 29]. Available from: http://hdl.handle.net/10222/56323.

Council of Science Editors:

Martinez-Farina C. Investigations into the Biosynthesis, Derivatization, and Purification of Jadomycins. [Masters Thesis]. Dalhousie University; 2015. Available from: http://hdl.handle.net/10222/56323

3. Marx, Vanessa. Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione.

Degree: PhD, Department of Chemistry, 2011, Dalhousie University

The development of the interrupted Nazarov cyclization of allenyl vinyl ketones is presented. The intermediate oxyallyl cation, derived from an allenyl vinyl ketone, may be trapped efficiently by a divergent array of nucleophilic species generating functionalized cyclopent-2-enone products. Allenyl vinyl ketones are also a versatile source of cyclic molecules via a tandem reaction sequence terminated via reaction with acyclic dienes, cyclic dienes, aza-heterocycles, electron-rich alkenes, or styrenes by the formation of an additional ring by a [4 + 3] and/or [3 + 2] cyclization or by the formation of one additional carbon-carbon bond. The bicyclic compounds generated by these processes are densely substituted, and would be difficult to access as succinctly in other ways. The products of these interrupted Nazarov reactions generally reflect excellent regio- and stereoselectivity in the trapping reaction. In some instances, equilibrating conditions were shown to enhance the proportion of one product at the expense of another or to provide a different carbon skeleton. This process appears fairly general, and can be conducted with unsubstituted or alkyl, aromatic, or heteroaromatic allenyl vinyl ketones. The exceptional affinity of allenyl vinyl ketones to undergo interrupted Nazarov reactions is likely a result of the increased longevity of the intermediate oxyallyl cation, due in part to the increased resonance stabilization provided by the allene unit. The high regioselectivity noted in the trapping process was computationally and experimentally confirmed to be a result of a localization of the positive charge in the intermediate oxyallyl cation. The application of this recently developed methodology towards the synthesis of the natural product (+)-roseadione is also described. The tandem Nazarov/[4 + 3] cascade of allenyl vinyl ketones provides a unique manner in which to access the tricyclic core of this cyclooctanoid natural product, a molecule which, to date, has never been synthesized. Advisors/Committee Members: Dr. Louis Barriault (external-examiner), Dr. Mark Stradiotto (graduate-coordinator), Dr. David L. Jakeman (thesis-reader), Dr. Ian R. Pottie (thesis-reader), Dr. Laura Turculet (thesis-reader), Dr. D. Jean Burnell (thesis-supervisor), Not Applicable (ethics-approval), Not Applicable (manuscripts), Not Applicable (copyright-release).

Subjects/Keywords: Allenes; Allenyl Vinyl Ketones; Interrupted Nazarov Reactions; Oxyallyl Cations; [4 + 3] Cyclizations; [3 + 2] Cyclizations; Bicyclic Ring Systems; Eight Membered Ring Systems

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Marx, V. (2011). Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione. (Doctoral Dissertation). Dalhousie University. Retrieved from http://hdl.handle.net/10222/13885

Chicago Manual of Style (16th Edition):

Marx, Vanessa. “Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione.” 2011. Doctoral Dissertation, Dalhousie University. Accessed May 29, 2020. http://hdl.handle.net/10222/13885.

MLA Handbook (7th Edition):

Marx, Vanessa. “Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione.” 2011. Web. 29 May 2020.

Vancouver:

Marx V. Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione. [Internet] [Doctoral dissertation]. Dalhousie University; 2011. [cited 2020 May 29]. Available from: http://hdl.handle.net/10222/13885.

Council of Science Editors:

Marx V. Development of the Interrupted Nazarov Cyclization of Allenyl Vinyl Ketones, with Application to the Total Synthesis of the Cyclooctane Natural Product Roseadione. [Doctoral Dissertation]. Dalhousie University; 2011. Available from: http://hdl.handle.net/10222/13885

.