Chemical Society Seminar: Xiaoguang Lei - Natural Product Synthesis as a Driving Force to Address the Antibiotic Resistance Crisis
Abstract:
Natural products and their derivatives have long been used as medicinal agents, and they still make up a significant fraction of clinically approved drugs. Natural product total synthesis provides a rich and unparalleled opportunity to develop new synthetic transformations, conceive novel and general strategies to access complex structures, and study the mechanism of action of bioactive targets. The combination of the tools and principles of chemistry, together with the tools of modern biology, allows us to create complex synthetic and natural molecules, comprising processes with novel biological, chemical and physical properties. This lecture will illustrate the opportunities that lie at this interface between synthetic organic chemistry, chemical biology as well as drug discovery endeavors by describing a series of examples that we are actively working on in our laboratory. Through total synthesis applying the state-of-the-art new synthetic strategies such as sequential C-H functionalizations, we are identifying a number of new natural product-derived antibiotics targeting tuberculosis or Gram-negative bacteria, which directly or indirectly block drug resistance with novel mode of actions. Such molecules, are applied in combination with first generation antibiotics to overcome resistance and rescue the activity of our current antibiotic arsenal.
Bio:
Prof. Dr. Xiaoguang Lei was born and raised in Beijing, China. He obtained BSc degree in chemistry from Peking University in 2001. He then moved to Boston and conducted his PhD research on natural product synthesis and chemical biology under the supervision of Prof. John. A. Porco at Boston University. He received Ph.D. in 2006, and then conducted his postdoctoral training in bioorganic chemistry with Prof. Samuel J. Danishefsky at Columbia University in New York City. In early 2009, Dr. Lei returned back to China, and started his independent research career as a Principal Investigator and Director of Chemistry Center at the National Institute of Biological Sciences (NIBS) in Beijing. In early 2014, he received a tenured full professorship from Peking University, and moved his research group to the College of Chemistry at Peking University. He also joined the Peking-Tsinghua Center for Life Sciences as a senior PI. The major research areas of Prof. Lei's laboratory are: natural product total synthesis, chemical biology and drug discovery. He has accomplished many total syntheses of the structurally complex and bioactive natural products and systematically used small molecule probes including natural products to dissect the fundamental cellular processes such as apoptosis and programmed necrosis (necroptosis), and illuminated a number of new molecular mechanisms. He has also developed many first-in-class drug candidates for the treatment of cancers and infectious diseases.
Prof. Lei has received many academic awards including: the 2018 David Ginsburg Lectureship Award, the 2018 CCS-BASF Young Investigator Award, the 2017 Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry, the 2017 Swiss Chemical Society Lectureship Award, the 2015 Chemical Society of Japan Lectureship Award, the 2014 Roche Young Investigator Award, the 2013 International Chemical Biology Society (ICBS) Young Chemical Biologist Award, the 2013 Servier Young Investigator Award, the 2013 Thieme Chemistry Journal Award, and the 2010 IUPAC Young Chemist Award. Now he is an Editor for Bioorganic & Medicinal Chemistry.