Date of Award
Chemistry and Biochemistry
The increasing prevalence of bacterial resistance to antibiotics is an epidemic where once easily treated infectious illnesses are becoming more difficult to treat, leading to prolonged suffering, exacerbated medical costs, and sometimes death. Methicillin-Resistant S. aureus (MRSA) is a strain of the Staph Infection causing bacteria that is resistant to penicillin-like beta lactam antibiotics and occurs at a high incidence in several countries in Europe, the Americas, and the Asia-Pacific region. In a routine screening of plant extracts, an extract of American Sycamore leaves (Plantus occidentalis) was noted to show promising activity against the experimental MRSA strain included in the screening panel. However, the identified active components known as plantanosides [kaempferol 3-O-Î±-l-(2â€³,3â€³-di-E-p-coumaroyl)rhamnoside, kaempferol 3-O-Î±-l-(2â€³-E-p-coumaroyl-3â€³-Z-p-coumaroyl)rhamnoside, kaempferol 3-O-Î±-l-(2â€³ Z-p-coumaroyl-3â€³-E-p-coumaroyl)rhamnoside, kaempferol 3-O-Î±-l-(2â€³,3â€³-di-Z-p coumaroyl)rhamnoside)] obtained by isolation from their natural source are not a commercially viable solution as large scale preparation is uneconomic. For this reason, synthetic routes will be more efficient for the commercial development of novel treatments. This study details the isolation of two natural products which 1) contain the kaempferol and rhamnose portions of the plantanosides (afzelin) and 2) a closely related quercetin rhamnoside derivative (quercitrin, which would allow evaluation of important structure-activity-relationship for antibiotic activity) and exploratory synthesis efforts to derivatize these natural products into analogs of the antibiotic plantanosides. Analogue synthesis was not achieved, but this synthetic strategy to achieve esterification at the hydroxyls of the rutinose portion of rutin (a model compound chosen for quercitrin) shed light into the behavior of the kaempferol core and rhamnose portions of the antibiotic plantanosides; namely, it was concluded that the phenolic hydroxyls of the core have the greatest reactivity which causes complications when attempting esterification at the sugar moiety hydroxyls. This knowledge contributes to the foundation for a possible solution to the MRSA epidemic.
Ramsaroop, Taylor, "Quercitrin and Afzelin Isolation: Chemical Synthesis of a Novel Methicillin-Resistant Staphylococcus Aureus (MRSA) Antibiotic Analogue" (2017). Honors Theses. 905.