On the origin of siphonariid polypropionates: total synthesis of caloundrin B and its isomerization to siphonarin B
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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.
DegreeDoctor of Philosophy (Ph.D.)
SupervisorWard, Dale E.
CommitteeMajewski, Marek; Low, Nicholas H.; Pedras, Soledade C.
Copyright DateMarch 2012