Synthesis of D-alanyl-D-alanine dipeptide isosteres and cephalosporin prodrugs

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.

Name thesis:degree_name

Master of Science (M.S.)

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Chemistry

Grantor dc:publisher

Colorado State University. Libraries

Year dc:date.issued

1997

Authors dc:creator

• Gansle, Paul, Jr., author
• Williams, Robert M., advisor

• Catalysis
• Organic compounds -- Synthesis
• Antibiotics

Statement 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.

Language dc:language.iso

eng, English

Identifier URI

https://doi.org/10.25675/3.024673

OAI identifier oai:identifier

oai:mountainscholar.org:10217/235831