Natural products continue to inspire synthetic chemists to develop novel
methodologies to provide efficient and expedient syntheses of the target molecules.
Haterumalide NA aroused our interest and prompted development of four differing
methodologies. Three of the strategies pursued involved use of B-lactone scaffolds as
intermediates. Extensions of the nucleophile catalyzed, aldol-lactonization (NCAL)
reaction were also pursued and targeted toward alternative natural product targets.
The reactivity of the unexpectedly stable strained spirocycle, spiroepoxy-B-
lactone, was explored. Spiroepoxy-B-lactones exhibited a wide range of reactivity, but
largely rearranged to tetronic acids. The desired reaction manifold remained inaccessible
and led to application of the NCAL process to tetrahydrofuran-fused B-lactones. Several
tetrahydrofuran-fused B-lactones were prepared, which displayed low
diastereoselectivity. The diastereoselectivity could be somewhat improved in a double
diastereoselective NCAL process with varied solvent systems, yet the carbocyclic
analogues gave much more promising results. The use of carbocycle-fused !-lactones
ultimately culminated in a double diastereoselective NCAL process, and overall led to improvements in diastereoselectivities from 1:1-2 up to >19:1. Further expansion of the
substrate scope for the NCAL process was studied for application to bridged tricyclic B-
lactones, access to carbocycle-fused y-lactones, and towards development of a dynamic
kinetic resolution NCAL process.
With our interest aimed at haterumalide NA, a modified Negishi cross coupling
between zincates and dichloroolefins was also revisited. The stringent anhydrous
reaction conditions led to reexamination of initial leads, which provided user-friendly
anhydrous conditions by utilizing commercially available anhydrous solvent. However,
application was implemented solely to a simplified model system.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2010-08-8405 |
| Date | 2010 August 1900 |
| Creators | Morris, Kay A. |
| Contributors | Romo, Daniel |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | thesis, text |
| Format | application/pdf |
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