Synthesis of D-alanyl-D-alanine dipeptide isosteres and cephalosporin prodrugs
| dc.contributor.author | Gansle, Paul, Jr., author | |
| dc.contributor.author | Williams, Robert M., advisor | |
| dc.date.accessioned | 2022-11-28T17:44:47Z | |
| dc.date.available | 2022-11-28T17:44:47Z | |
| dc.date.issued | 1997 | |
| dc.description.abstract | Resistance to vancomycin by enterococci is of great clinical importance. Vancomycin inhibits bacterial growth by binding to terminal D-alanyl-D-alanine linkages in the growing peptidoglycan cell wall. Synthesis of dipeptide isosteres which may be incorporated into the growing cell wall is described. Previously published syntheses were employed as well as a Wittig reaction using a chiral Wittig reagent, a reaction not used in the synthesis of isosteres before. If the isosteres are directly incorporated, cell wall synthesis will be inhibited. Additionally, it is believed that the isosteres will act as mechanism-based inhibitors of the enzymes which are responsible for vancomycin resistance. Delivery of dipeptides into bacteria is difficult due to selective transport mechanisms. Several reports have been made which use a cephalosporin prodrug with a dual mode of action. Antibiotics are coupled to cephalosporin intermediates and produce a compound which is capable of acting as an antibiotic on its own as well as delivering the coupled antibiotic into the periplasm by enzymatic hydrolysis of the prodrug. A novel phase-transfer reaction was used to couple dipeptide isosteres to a cephalosporin intermediate. | |
| dc.format.medium | masters theses | |
| dc.identifier.uri | https://hdl.handle.net/10217/235831 | |
| dc.language | English | |
| dc.language.iso | eng | |
| dc.publisher | Colorado State University. Libraries | |
| dc.relation | Catalog record number (MMS ID): 991003547279703361 | |
| dc.relation | QD505.G35 1997 | |
| dc.relation.ispartof | 1980-1999 | |
| dc.rights | Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright. | |
| dc.subject | Catalysis | |
| dc.subject | Organic compounds -- Synthesis | |
| dc.subject | Antibiotics | |
| dc.title | Synthesis of D-alanyl-D-alanine dipeptide isosteres and cephalosporin prodrugs | |
| dc.type | Text | |
| dcterms.rights.dpla | This Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). | |
| thesis.degree.discipline | Chemistry | |
| thesis.degree.grantor | Colorado State University | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.S.) |
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