| dc.identifier.uri | http://hdl.handle.net/1951/55972 | |
| dc.identifier.uri | http://hdl.handle.net/11401/71577 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Thesis | |
| dcterms.abstract | β-Lactams are four-membered cyclic amides which can be found in many biologically active compounds. β-Lactams may possess two stereocenters. In enantiopure form, β-lactams can be used as chiral building blocks for the synthesis of various biologically relevant compounds, such as antibacterial drugs, antitumor agents, peptides, peptidomimetics and enzyme inhibitors. In addition, fluorine-containing β-lactams have drawn substantial interests among bioorganic and medicinal chemists. Studies have shown that the incorporation of fluorine efficiently blocks metabolism of the drug molecules, especially by cytochrome P-450 family of enzymes, providing improved pharmacokinetic properties. Different diastereomers of fluorine-containing β-lactams with high enantiopurity were synthesized utilizing a base-catalyzed C4-specific epimerization. Highly enantioenriched cis-β-lactams were obtained using the Staudinger [2+2] ketene-imine cycloaddition reaction, followed by kinetic enzymatic resolution. Ozonolysis of an exocyclic double bond of the enantioenriched cis-β-lactam afforded the key intermediate for selective epimerization, i.e., a C4-formyl-β-lactam. The epimerization reaction was optimized for the isolation of trans-β-lactams. A difluorovinyl group was incorporated through a Wittig reaction, and subsequent modification of the substituents gave the desired 4-difluorovinyl-β-lactams. Using this protocol, a novel trans-difluorovinyl-β-lactam, (3S,4S)-1-(tert-butoxycarbonyl)-3-triisopropylsiloxy-4-(2,2-difluoroethenyl)azetidin-2-one with excellent enantiopurity, was obtained. These novel cis- and trans-fluorine-containing β-lactams can be used for the synthesis of fluorine-containing α-hydroxy-β-amino acids and their congeners or for the incorporation of fluorines into biologically active compounds via the β-lactam synthon method to investigate the effects of the fluorine moieties on their biological activities. | |
| dcterms.available | 2012-05-17T12:20:16Z | |
| dcterms.available | 2015-04-24T14:48:00Z | |
| dcterms.contributor | Kathlyn A. Parker. . | en_US |
| dcterms.contributor | Iwao Ojima. Frank W. Fowler. | en_US |
| dcterms.creator | Chen, Wen | |
| dcterms.dateAccepted | 2012-05-17T12:20:16Z | |
| dcterms.dateAccepted | 2015-04-24T14:48:00Z | |
| dcterms.dateSubmitted | 2012-05-17T12:20:16Z | |
| dcterms.dateSubmitted | 2015-04-24T14:48:00Z | |
| dcterms.description | Department of Chemistry | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | Chen_grad.sunysb_0771M_10548.pdf | en_US |
| dcterms.identifier | http://hdl.handle.net/1951/55972 | |
| dcterms.identifier | http://hdl.handle.net/11401/71577 | |
| dcterms.issued | 2011-05-01 | |
| dcterms.language | en_US | |
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Previous issue date: 1 | en |
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Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Chemistry | |
| dcterms.subject | β-Amino Acid Synthesis, β-lactams, epimerization, Fluorine, Schiff base, trans β-lactams | |
| dcterms.title | Asymmetric Synthesis of Novel Fluorine-Containing β-Lactams for Application to Unnatural β-Amino Acid Synthesis | |
| dcterms.type | Thesis | |
