{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Asymmetric Synthesis of Novel Fluorine-Containing \u03b2-Lactams for Application to Unnatural \u03b2-Amino Acid Synthesis","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/1951/55972"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"\u03b2-Lactams are four-membered cyclic amides which can be found in many biologically active compounds. \u03b2-Lactams may possess two stereocenters. In enantiopure form, \u03b2-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 \u03b2-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 \u03b2-lactams with high enantiopurity were synthesized utilizing a base-catalyzed C4-specific epimerization. Highly enantioenriched cis-\u03b2-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-\u03b2-lactam afforded the key intermediate for selective epimerization, i.e., a C4-formyl-\u03b2-lactam. The epimerization reaction was optimized for the isolation of trans-\u03b2-lactams. A difluorovinyl group was incorporated through a Wittig reaction, and subsequent modification of the substituents gave the desired 4-difluorovinyl-\u03b2-lactams. Using this protocol, a novel trans-difluorovinyl-\u03b2-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 \u03b2-lactams can be used for the synthesis of fluorine-containing \u03b1-hydroxy-\u03b2-amino acids and their congeners or for the incorporation of fluorines into biologically active compounds via the \u03b2-lactam synthon method to investigate the effects of the fluorine moieties on their biological activities."},{"label":"dcterms.available","value":"2015-04-24T14:48:00Z"},{"label":"dcterms.contributor","value":"Iwao Ojima.  Frank W. Fowler."},{"label":"dcterms.creator","value":"Chen, Wen"},{"label":"dcterms.dateAccepted","value":"2012-05-17T12:20:16Z"},{"label":"dcterms.dateSubmitted","value":"2012-05-17T12:20:16Z"},{"label":"dcterms.description","value":"Department of Chemistry"},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"Chen_grad.sunysb_0771M_10548.pdf"},{"label":"dcterms.issued","value":"2011-05-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2012-05-17T12:20:16Z (GMT). No. of bitstreams: 1\nChen_grad.sunysb_0771M_10548.pdf: 3651317 bytes, checksum: 6c053854f2c0f214d630bbec7edebb11 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"\u03b2-Amino Acid Synthesis, \u03b2-lactams, epimerization, Fluorine, Schiff base, trans \u03b2-lactams"},{"label":"dcterms.title","value":"Asymmetric Synthesis of Novel Fluorine-Containing \u03b2-Lactams for Application to Unnatural \u03b2-Amino Acid Synthesis"},{"label":"dcterms.type","value":"Thesis"},{"label":"dc.type","value":"Thesis"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/79%2F44%2F72%2F79447221984835190980064540638802878681/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/79%2F44%2F72%2F79447221984835190980064540638802878681","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}