Two research projects are described: studies of the synthesis of alpha-amino-alpha-alkylsilanes, the synthetic precursor of silanediol-based protease inhibitors, and the synthesis and stability evaluation of silanediol amino acids with an unprecedently unhindered silanediol group. Two methods were investigated as approaches to alpha-amino-alpha-alkylsilanes. First, a silicon-substituted aziridine was chosen as the precursor of an alpha-amino-alpha-alkylsilane via ring opening reactions with carbon nucleophiles. Silyl-substituted aziridines 2-24 and 2-30 were prepared via direct lithiation/silylation of aziridine and employed as substrates for ring opening reactions. In spite of many attempts to ring open these silylaziridines and prepare ?-amino-?-alkylsilanes, optimization of the reaction conditions were unsuccessful. Secondly, alpha-chloro-alpha-benzylsilane 3-12 was prepared as the precursor of an alpha-amino-alpha-alkylsilane via lithiation/benzylation. The alkylation at carbon alpha to silicon to give chloromethylsilane 3-14 was successful when using n-butyllithium for lithiation, which could be explained by the steric encumbrance inherent in the structure. Several attempts for nucleophilic displacement of chloride to obtain alpha-chloro-alpha-benzylsilane 3-11 were unsuccessful possibly due to the steric effect as well as the electronic effect of silicon on the alpha carbon which made the chloride less reactive toward nucleophilic substitution. The silanediol amino acid 4-1 was synthesized originally as a potential arginase inhibitor. Although the expected biological activity was not observed, the studies on silanediol-siloxane distribution of the silanediol amino acid revealed the unique properties of this compound. Under basic conditions, the silanediol amino acid was mainly stable in monomeric form. As the pH decreased, the silanediol amino acid gave a mixture of siloxanes which consisted of a variety of stereoisomers. With available instrumental techniques, monomer, dimers and trimers of the silanediol amino acid were identified. / Chemistry
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/3719 |
| Date | January 2008 |
| Creators | Kim, Jin Kyung |
| Contributors | Sieburth, Scott McNeill, Williams, John R., Davis, Franklin A., Berry, Donald H. |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 162 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/3701, Theses and Dissertations |
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