Day 1 :
Keynote Forum
Hans-Dieter Arndt
Friedrich-Schiller-University, Germany
Keynote: Total synthesis and functional studies of parthenolides and urukthapelstatins
Time : 09:30-10:00
Biography:
Hans-Dieter Arndt is an enthusiastic synthetic organic chemist with expertise in medicinal chemistry and chemical biology. He studied chemistry at the universities of Ulm, Marburg, Germany, and Imperial College, London, UK. He has obtained his PhD degree in 2002 at Humboldt-University, Berlin, Germany. After postdoctoral research at CalTech, Pasadena, USA, he launched his independent career at the Max-Planck-Institute of Molecular Physiology, Dortmund, Germany. In 2011, he moved to Friedrich-Schiller University, Jena, Germany, where he currently holds the Chair of Organic Chemistry. He is the Director of the Institute of Organic and Macromolecular Chemistry and currently he is serving as Vice-Dean. His research interests include natural product synthesis, synthesis design, method development, and Chemical Biology and Chemical Ecology research.
Abstract:
The total synthesis of natural products is an important enabling step toward dedicated mode of action studies. Two case studies from our laboratory will be presented in the lecture. We have recently reported on an efficient total synthesis of the potent cytotoxin urukthapelstatin A. This synthesis utilizes a combination of thiolactonization and aza-Wittig ring contraction reactions to obtain high yields of the strained macrocycle. By using this technology structural variations are easily implemented. X-ray structures and biological activities will be presented. Based on these findings, the chemistry workflow was adapted and transferred to solid phase. The efficiency of this new methodology is demonstrated by the swift first total synthesis of aurantizolicin, a cryptic metabolite from Streptomyces aurantiacus. Structure and Stereochemistry of the scarce natural product has thereby been unambiguously assigned. Progress toward studying the bioactivity and mode-of action of these polyazole Cyclopeptides will be discussed. On the other hand, many methylene g-lactone terpenes feature remarkable anti-inflammatory and neuritogenic activity. In this regard, the germacrane sesquiterpene parthenolide form the medicinal plant feverfew (Tanacetum parthenium) caught our interest. While semisynthetic approaches to and non-selective syntheses of this highly active natural product have been reported, incomplete access to stereoisomers and to derivatives has impeded medicinal chemistry and mode of action studies. Here, we will present the first stereoselective total synthesis of parthenolide that enables access to all its possible stereoisomers as well. It employs novel trisubstituted allylborane reagents that exert excellent stereocontrol as well as an efficient ring closure (80% yields) of the peculiar 10-membered ring scaffold
Keynote Forum
K Michal Pietrusiewicz
Maria Curie-Skłodowska University, Poland
Keynote: Making BH3 to cleave strong chemical bonds with an added chemoselectivity gain
Time : 10:00-10:30
Biography:
K Michał Pietrusiewicz has his expertise in the field of organic chemistry, stereochemistry, stereoselective synthesis, organophosphorus synthesis and use of organophosphorus compound as synthetic reagents as well as ligands in asymmetric processes catalyzed by transition metal complexes.
Abstract:
The P=O bond is one of the strongest of those commonly encountered. The large amount of energy released during its formation acts as the driving force for many important transformations in organic chemistry; the Wittig, Mitsunobu, and Appel reactions being classic examples. Conversely, this same bond strength causes considerable difficulties in the deoxygenation of P=O-containing species; the conversion being highly desirable, enabling access to their PIII counterparts serving very often as valuable ligands and organo catalysts. Due to the inert nature of P-C bonds, options do exist for the reduction of most tertiary phosphine oxides, which are successfully deoxygenated with strong reducing agents such as metal hydride and silanes. In contrast to tertiary phosphine oxides, the deoxygenation of phosphorus(V) acid esters and amides by these agents is effectively impossible due to the need to break the immensely strong and inert P=O bond in the presence of relatively weak and more reactive P-O and P-N bonds. This long-standing problem in organophosphorus synthesis is solved by use of BH3, a mild reducing agent, which chemo selectively cleaves the P=O bond in phosphinate and phosphonate derivatives leaving the P-O and/or P-N bonds intact. The success is owed to the assistance of the α-heteroatom group present in the P=O containing species which is directing the chemoselective action of BH3. The P=O bond is deoxygenated with clean inversion of configuration at P. A mechanistic picture of the reduction process coherent with all the observations is proposed. This simple one-pot procedure was applied for a wide range of P-O and P-N-containing phosphinate/phosphonate compounds to produce the corresponding borane-protected PIII products in good yields. The P-BH3 product can be easily deprotected to produce the free PIII ester or amide derivative. The availability of this methodology opens up previously unavailable synthetic options in organophosphorus chemistry, some of which are exemplified.
Keynote Forum
Thomas Bannister
The Scripps Research Institute-Florida, USA
Keynote: Addressing the opioid crisis with safer opioid pain relievers: Is it possible?
Time : 10:30-11:00
Biography:
Thomas Bannister is a Senior Scientific Director of Molecular Medicine at Scripps Research in Jupiter, Florida, world leader in nonprofit biomedical research. He received his scientific training at Wabash College, Yale University, and Indiana University. AT, IU he studied under Professor William R Roush. He then worked in the pharmaceutical industry as a Drug Discovery Medicinal Chemist for 14 years. He came to Scripps Florida in 2005 to actively collaborate on project teams seeking breakthrough therapies for various cancers, neurological disorders, and pain.
Abstract:
Compounds that activate opioid receptors, especially the mu opioid receptor (MOR), have been used extensively since antiquity for pain relief and euphoria. Unfortunately poppy-derived compounds (e.g, morphine) as well as their modern synthetic functional mimics (e.g., fentanyl) also can elicit a host of unwanted side effects, include life-threatening respiratory suppression. In fact, the ongoing worldwide opioid crisis has made the dangers of opioid abuse quite clear. In our studies we have made probe molecules and potential drugs to untangle the mechanistic details of MOR signaling and its pharmacological effects. A wide respiratory safety window appears to require robust G-protein-mediated MOR signaling with almost no measurable beta arrestin involvement. We have identified functionally biased and drug-like MOR agonists with this specific profile. Further, we have found them to be robust pain relievers in mice, with greatly improved respiratory safety relative to currently available opioid drugs.
Keynote Forum
Alexander Olegovich Terent’ev
N D Zelinsky Institute of Organic Chemistry-RAS, Russia
Keynote: New organic peroxides with valuable properties
Time : 11:00-11:30
Biography:
Alexander Olegovich Terent’ev has completed his PhD and DSc degrees in 2000 and 2009 respectively. Currently, he is Professor at D Mendeleev University of Chemical Technology of Russia; Head of laboratory at N D Zelinsky Institute of Organic Chemistry RAS, and Head of laboratory in All-Russian Research Institute of Phytopathology. His research interests are organic chemistry, medical and agricultural chemistry, chemical technology. He published 120 research papers, and 30 patents.
Abstract:
In the last decade, the progress of chemistry of organic peroxides was catalyzed by numerous reports of their antimalarial, anthelmintic, antitumor, growth regulation and antitubercular activity. The importance of these studies is illustrated by the 2015 Nobel Prize in Medicine awarded to Youyou Tu for the discovery and development of Artemisinin. In our work we developed methods for synthesis of various types of cyclic and linear peroxides usng of H2O2 and carbonyl compounds. Cyclic peroxides: ozonides, tetraoxanes, and tricyclic monoperoxides demonstrate prospective anticancer and antiparasitic properties
Keynote Forum
Alexander Olegovich Terent’ev
Keynote: New organic peroxides with valuable properties
Time : 11:00-11:30
Biography:
Alexander Olegovich Terent’ev has completed his PhD and DSc degrees in 2000 and 2009 respectively. Currently, he is Professor at D Mendeleev University of Chemical Technology of Russia; Head of laboratory at N D Zelinsky Institute of Organic Chemistry RAS, and Head of laboratory in All-Russian Research Institute of Phytopathology. His research interests are organic chemistry, medical and agricultural chemistry, chemical technology. He published 120 research papers, and 30 patents.
Abstract:
In the last decade, the progress of chemistry of organic peroxides was catalyzed by numerous reports of their antimalarial, anthelmintic, antitumor, growth regulation and antitubercular activity. The importance of these studies is illustrated by the 2015 Nobel Prize in Medicine awarded to Youyou Tu for the discovery and development of Artemisinin. In our work we developed methods for synthesis of various types of cyclic and linear peroxides usng of H2O2 and carbonyl compounds. Cyclic peroxides: ozonides, tetraoxanes, and tricyclic monoperoxides demonstrate prospective anticancer and antiparasitic properties