This thesis research presents the synthesis and first application of bis-amino acid-based spiroligomers towards the development of organocatalysis, from small molecules to moderate size spiroligomers, and to macromolecules. By synthesizing a toolbox of cyclic monomers called "bis-amino acids", the Schafmeister group has developed an approach to construct both small and macromolecules named "Spiroligomers". These molecules arrange catalytic functional groups in a shape-persistent and programmable backbone. Unlike proteins and small peptides, spiroligomers do not fold; rather, their polycyclic backbone structures are controlled by the sequence and stereochemistry of the component monomers. Firstly, we demonstrated a structure/catalytic activity relationship together with computational modeling that suggests that a specific hydrophobic interaction between the modified pro4 catalyst and the aldehyde substrate is responsible for an observed rate enhancement in the aldol reaction. For the moderate size molecules, several spiroligomer libraries were prepared through solid phase or solution phase synthesis and screened for either the alcohol kinetic resolution reaction or the aldol reaction. The poor activity and selectivity suggest that the scaffolds involved cannot create the necessary chiral environment for asymmetric catalysis. Finally, a synthetic method of macromolecules using cross metathesis coupling was developed and a series of tetra-functionalized macrocyclic spiroligomers were synthesized. Three of these macromolecules were examined as asymmetric catalysts in the aldol reaction and gave moderate activity and selectivity. The NMR analysis of these macromolecules indicates their dynamic nature. As the first application of bis-amino acid based macromolecules in organocatalysis area, although these catalysts only generated moderate activity and selectivity, they provided evidence that changing the configuration of one stereocenter of the fourteen available within these macromolecules can alter the selectivity. This synthetic methodology also provides an effective way to create more complicated pocket like spiroligomer macromolecules for the future applications in catalysis and molecular recognition. / Chemistry
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/4094 |
| Date | January 2014 |
| Creators | Zhao, Qingquan |
| Contributors | Andrade, Rodrigo B., Schafmeister, Christian, Wuest, William M., Cannon, Kevin C. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 561 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/4076, Theses and Dissertations |
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