Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Chia-Jui Lee
National Health Research Institutes, Taiwan
Posters & Accepted Abstracts: J Clin Cell Immunol
A rapid increase in multidrug-resistant bacteria and slow development of new antibiotics has posed a great threat to global public health. Notoriously, infection caused by Methicillin-Resistant Staphylococcus aureus (MRSA) has become one of the most serious problems in hospitals due to its high mortality rate. Thus, developing new antibiotics against these multidrugresistant bacteria is urgently demanded. A class of natural products possess a gem-dimethyl tetracyclic carbon skeleton has been reported to show potent anti-MRSA activities. Among them, Fasamycins A and B were found to inhibit the FabF enzyme associated with the biosynthesis of type-II fatty acid (FASII). The other congeners (e.g., 6) not only showed activities against various MRSA, but also circumvent �-lactam resistance in combination with Imipenem. These biological features make this series of natural products become a potential hit and/or lead for further structural modifications to seek novel antibiotics. We have completed a concise total synthesis of Tetarimycin A, (±)-Naphthacemycin A9, (±)-Fasamycin A and (±)-ABX in a highly convergent manner using efficient anion annulation in the last stage. With reductive olefin coupling, intermolecular Friedel- Crafts acylation and Suzuki-Miyaura coupling as key operations, these synthetic approaches become economic and general for potential antibiotics possessing a linear tetracyclic carbon skeleton.
Chia-Jui Lee completed his PhD from National Taiwan Normal University in 2016. He is currently a Post-doctoral in the area of new drug development in the Institute of Bio-technology and Pharmaceutical Research, National Health Research Institutes in Taiwan.
E-mail: roylee8819@gmail.com