On the origin of siphonariid polypropionates: total synthesis of caloundrin B and its isomerization to siphonarin B
| dc.contributor.advisor | Ward, Dale E. | en_US |
| dc.contributor.committeeMember | Majewski, Marek | en_US |
| dc.contributor.committeeMember | Low, Nicholas H. | en_US |
| dc.contributor.committeeMember | Pedras, Soledade C. | en_US |
| dc.creator | Becerril-Jimenez, Fabiola | en_US |
| dc.date.accessioned | 2013-01-03T22:28:26Z | |
| dc.date.available | 2013-01-03T22:28:26Z | |
| dc.date.created | 2012-03 | en_US |
| dc.date.issued | 2012-04-06 | en_US |
| dc.date.submitted | March 2012 | en_US |
| dc.description.abstract | It has been hypothesized that the polypropionates isolated from Siphonaria zelandica, siphonarin B, caloundrin B, baconipyrone A, and baconipyrone C, originate by non-enzymatic processes on a common ‘acyclic’ biosynthetic precursor. In previous work in the Ward group, the putative common precursor was synthesized and transformed into siphonarin B, baconipyrone A, and baconipyrone C. However, caloundrin B was not detected in these experiments and its origin remained as a missing piece of the puzzle. Thereafter, it was hypothesized that caloundrin B could be an unstable biosynthetic product from which the formation of the other polypropionates could be readily explained. To test that hypothesis, a new strategy to synthesize caloundrin B was proposed. This thesis describes and analyzes the manner in which the first synthesis of ent-caloundrin B was achieved. The two key steps towards the target molecule involved the synthesis of the trioxaadamantane motif and the assembly of the complete skeleton of ent-caloundrin B via a novel aldol coupling between the trioxaadamantane-containing ketone and the γ-pyrone-containing aldehyde, that proceeds with kinetic resolution. The studies toward the synthesis of caloundrin B allowed the development of new methodologies and the application of a recently disclosed protocol to design aldol reactions that proceed with kinetic resolution. During the course of those studies, a non-linear effect was identified and characterized. After completion of the synthesis, ent-caloundrin B was isomerized to ent-siphonarin B under thermodynamic conditions, thus confirming the relative and absolute configuration of ent-caloundrin B. This transformation leads to the conclusion that caloundrin B is much less stable than siphonarin B; as a consequence, caloundrin B cannot be an artifact of isolation as previously proposed, but instead, it could be the biosynthetic product from which siphonarin B, baconipyrone A, and baconipyrone C are formed. | en_US |
| dc.identifier.uri | http://hdl.handle.net/10388/ETD-2012-03-369 | en_US |
| dc.language.iso | eng | en_US |
| dc.subject | polypropionates | en_US |
| dc.subject | natural products | en_US |
| dc.subject | aldol reactions | en_US |
| dc.title | On the origin of siphonariid polypropionates: total synthesis of caloundrin B and its isomerization to siphonarin B | en_US |
| dc.type.genre | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Chemistry | en_US |
| thesis.degree.discipline | Chemistry | en_US |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) | en_US |