The inaugural Art and Science of Total Synthesis of Natural and Designed Molecules for Biology and Medicine (ASTS-NDM 2024) symposium brought together some of the world’s most renowned organic chemists Oct. 2-4 at the historic Club de la Chasse et de la Nature in Paris. Hosted by Rice University’s Global Paris Center, the event explored the evolving role of synthetic organic chemistry and total synthesis of natural and designed molecules in fields such as medicine, materials science and chemical biology.
The three-day symposium attracted leading figures in synthetic organic chemistry, featuring 18 speakers who presented their latest research and insights. Among them were Rice’s Kyriacos Costa “K.C.” Nicolaou, the Harry C. and Olga K. Wiess Professor of Chemistry, and Nobel laureates Ben Feringa and Morten Meldal.
Nicolaou, a pioneering synthetic organic chemist known for his work in cancer therapies who has synthesized nearly 200 naturally occurring molecules, highlighted the transformative potential of total synthesis, emphasizing its capacity to recreate natural molecules and develop superior synthetic analogs with therapeutic properties.
He discussed how total synthesis has revolutionized drug development, pointing to his work with Taxol, a key chemotherapy drug for ovarian and breast cancer, and calicheamicin, a component in antibody-drug conjugates (ADCs). Nicolaou was the first to synthesize the first example of an ADC in 1998 using a calicheamicin analog as a payload that showed unique anticancer properties in mice, paving the way for the first clinical ADC (Mylotarg) produced by a company (Lederly, now Pfizer) in 2000 and used to treat acute lymphocytic leukemia. Numerous other ADCs are currently in use as anticancer medications and many others are expected in the future for other therapies.
“We were going for the most difficult structures to synthesize,” Nicolaou said, explaining how the complexity of natural molecules inspires innovation and advancement of the art of total synthesis in the future. He encouraged young chemists to follow their talents with “passion, hard work and discipline,” asserting that total synthesis continues to push the boundaries of scientific discovery, especially in medicine.
Feringa, a Dutch chemist and recipient of the 2016 Nobel Prize in Chemistry, delivered a plenary lecture focusing on his advancements in molecular nanotechnology and catalysis. He discussed the role of catalysis in creating sustainable technologies and improving drug design and synthesis.
“We decided to make monodentate phosphorus ligands, and they work fantastic,” Feringa said, sharing how his team developed these catalysts in a single-step process that has since found applications in addressing global health issues such as tuberculosis.
Feringa emphasized the importance of organometallic reagents in stereoselective synthesis, detailing how his copper-catalyzed processes have contributed to pharmaceutical developments. He urged young scientists to tackle the “tremendous challenges” ahead, expressing optimism about chemistry’s potential to transform industries and address global problems.
Meldal, a Danish professor at the University of Copenhagen and winner of the 2022 Nobel Prize in Chemistry, delivered a speech on the importance of natural product synthesis. Meldal’s pioneering development of the CuAAC-click reaction has revolutionized both chemical and biological research. He reflected on the foundational role of chemistry in shaping human understanding. “Chemistry is everything,” he said, encouraging educators to teach molecular visualization skills early in students’ education.
Meldal also shared his journey through scientific discovery, emphasizing the unpredictability of research. “Discoveries are never what you expect,” he said, underscoring the importance of observation and adaptability in driving innovation. A portion of his speech focused on the challenges in solid phase synthesis, particularly the dwindling availability of polar resins, which are crucial for many synthetic processes.
Other distinguished organic and medicinal chemists who spoke at ASTS-NDM 2024 include Alois Fürstner (Max Planck Institute, Germany), whose transformative work in catalysis has advanced organometallic chemistry and total synthesis; Sarah Reisman (California Institute of Technology), a leading authority in natural product synthesis focusing on complex biologically active molecules; Ilan Marek (Technion, Israel), renowned for his contributions to stereoselective synthesis and innovative strategies for constructing molecular complexity; and Peter Somfai (Lund University, Sweden), a specialist in synthetic strategies and methods for developing biologically active compounds.
The symposium also featured speakers Kelly Chibale (University of Cape Town, South Africa), a pioneer in drug discovery for infectious diseases, including tuberculosis and malaria, through bioactive compound synthesis; Antonio Echavarren (Institute of Chemical Research of Catalonia, Spain), recognized for his groundbreaking work in gold-catalyzed reactions and the total synthesis of natural products; Jin-Quan Yu (The Scripps Research Institute), a trailblazer in C-H activation, developing catalytic systems to simplify complex molecule construction; and Erick Carreira (ETH Zurich, Switzerland), editor-in-chief of the American Chemical Society and an expert in asymmetric synthesis and the total synthesis of natural products with potential medical applications.
By bringing together researchers at the forefront of the field, the ASTS-NDM 2024 symposium emphasized how this area of chemistry has helped shape our modern world.
“The ASTS-NDM 2024 symposium not only celebrated the achievements of leading chemists but also explored the future of total synthesis in addressing global challenges in medicine and beyond,” said Angel Marti, a member of the ASTS-NDM 2024 organizing committee and the chair of Rice’s Department of Chemistry.