2016 Spring/Summer Semester Plenary Seminar at SKKU Department of Chemistry 이분열 교수, 아주대학교 “Translational Research in the Development of Polymerization Catalysts“화학적 지식의 경제성 창출? 가능한가? 화학이 돈이다! Place: Chemistry Bld. Rm 330118Time: 4:15~5:30 pm. =========================================================================================== Translational Research in the Development of Polymerization Catalysts (중합 촉매 개발을 통한 대학 개발 기술의 산업체 기술이전) Bun Yeoul Lee Department of Molecular Science and Technology, Ajou University, Suwon 443-749 Korea email@example.com 1) Olefin polymerizations In our laboratory, more than 100 new titanium and zirconium complexes have been preapred for olefin polymerizations for the last two decades. Especailly, organolithium compounds have been actively utilized in the construction of those complexes. The representative complexes1 and 2 can be prepared in two steps in Kg-scale, which exhibit high activity, high 1-octene incorporation, and high molecular weight in the ethylene/1-octene copolymerizations. Complex 1 is currently used in industry (LG) for the production of polyolefin elastomers (~80,000 T/y) and eventually complex 2was licensed out to Lotte Chem in 2011 with affront fee 600,000,000 Won. 2) CO2/epoxide copolymerization A highly active catalyst (3) was discovered for the CO2/epoxide copolymerization. Complex 3 showed a high TON up to ~20000 and a high turnover frequency (TOF) of ~20000 h-1 that produced a strictly alternating copolymer with a high molecular weight (Mn) of up to 300000. The catalyst was licensed out to SK in 2008 with affront fee 600,000,000 Won. 3) New compostable polymers from CO2 High-molecular-weight poly(1,4-butylene carbonate-co-terephthalate)s were prepared by condensation copolymerizations of 1,4-butanediol, dimethyl carbonate, and dimethyl terephthalate, which shows the comparable thermal properties to the commercialized compostable polyesters such as PLA, PHA, PBAT, and PBSA. The polymers were licensed out to Lotte Chem in 2014 with affront fee 500,000,000 Won.
제 목 : Evaluation of Trehalose Derivatives as Radiotracers Specific for Tuberculosis in Animal Models of Disease 연 사 : 이승서 교수님(University of Southampton) Evaluation of Trehalose Derivatives as Radiotracers Specific for Tuberculosis in Animal Models of Disease We are developing PET radiotracers specific to Mycobacterium tuberculosis (Mtb). In evaluating new treatments, [18F]-2-fluoro-2-deoxyglucose (FDG) has been shown to be a useful tool, but it is not highly correlated with bacterial burden. We are evaluating trehalose radiotracers which may be covalently incorporated in vivo into the Mtb cell wall to give a PET signal directly correlated to bacterial burden rather than reporting on inflammation or other host response. We have designed several [18F]-labeled trehalose derivatives and are evaluating them in animal models of tuberculosis. Two of the probes, [18F]-6-fluoro-6-deoxytrehalose (6-FTre) and [18F]-epi-4-fluoro-4-deoxytrehalose (epi-4-FTre) are chemically synthesized in a method similar to [18F]-2-fluoro-2-deoxyglucose (FDG) from peracetylated precursors, and one probe, [18F]-2-fluoro-2-deoxytrehalose (2-FTre), is chemoenzymatically synthesized in a one-pot, three-enzyme cocktail from [18F]-FDG. All three were initially evaluated in Mtb-infected rabbits by acquiring PET/CT scans and blood and urine samples for metabolism analysis. The 2-FTre probe is also currently being evaluated in a non-human primate model of tuberculosis. In initial experiments in Mtb-infected rabbits, the 6-FTre probe was rapidly metabolized to [18F]-6-fluoro- 6-deoxyglucose. However, the epi-4-FTre was metabolically stable and did label lesions in the rabbit lung. A typical signal-to-noise for labeling was 2-3:1. The 2-FTre gave a slightly higher signal-to-noise and also appeared to give some differential labeling when compared to FDG. However, we saw potential probe metabolism and decided to change to a marmoset model of tuberculosis, which should express lower levels of trehalase than rabbits. The 2-FTre is currently under evaluation in a marmoset model of disease and appears to be labeling lesions selectively. No metabolism is observed in blood or urine of the marmosets. The trehalose derived probes are demonstrating uptake in PET scans at the site of Mtb lesions. This technology will allow us to selectively label Mtb infection and monitor treatment in animals on experimental drug regimens.
안녕하세요. 다음주 화요일(3월 8일)에 Plenary Seminar가 진행됩니다. 참석 부탁드립니다. 감사합니다. ====================================== 제 목 : Pot Economy in Total Synthesis 연 사 : Prof.Yujiro Hayashi(Department of Chemistry, Tohoku University, Japan) 일 시 : 2016년 3월 8일(화) 오후 4시 15분 장 소 : 화학관 첨단강의실(330118호) -------------------------------------- Pot Economy in Total Synthesis Yujiro HayashiDepartment, Tohoku University, JapanE-mail: firstname.lastname@example.org://www.ykbsc.chem.tohoku.ac.jp One-pot operations are an effective method for both carrying out several transformations and forming several bonds in a single-pot, while at the same time cutting out several purifications, minimizing chemical waste generation, and saving time. Thus, a one-pot reaction can be not only efficient, but also green and environmentally friendly, and “pot-economy” should be considered in planning a synthesis.1 Organocatalyst is an effective catalyst to carry out several reactions in a same vessel. Our group2 and Jørgensen’s group3 independently discovered that diphenylprolinol silyl ether, which is easily synthesized from proline, is an effective organocatalyst in the reaction nvolving enamine and iminium ion as a reactive intermediate. We have been investigating the application of this catalyst to the one-pot synthesis of biologically active compounds. We have already reported three pot synthesis of (-)-oseltamivir, a neuraminidase inhibitor used in the treatment of human influenza, based on the diphenylprolinol silyl ether mediated Michael reaction of aldehyde and nitroalkene as a key step. Recently we have accomplished “one-pot” synthesis of (-)-oseltamivir without evaporation nor solvent exchange by the modification of the previous three pot synthesis.4 We further applied one-pot synthetic strategy to the total synthesis of prostaglandin E1methyl ester, and accomplished three “one-pot” synthesis of this biologically important molecule.5 Recently (S)-baclofen was synthesized via one-pot sequential reaction from the commercially available compounds.A recent progress in the one-pot synthesis will be described.
안녕하세요. 다음주 수요일(12월 30일) 세미나가 진행됩니다. 많은 참석 부탁드립니다. 감사합니다. ====================================== 제 목 : Developing a new ultrafast proving tool : challenging the chemical- and electronic dynamics of energy storage and solar cell systems 연 사 : 서현욱 박사 (Centre for Free-Electron Laser Science) 일 시 : 2015년 12월 30일 (수) 오전 11시 장 소 : 화학관 세미나실 (330226호실) -------------------------------------- Developing a new ultrafast proving tool : challenging the chemical- and electronic dynamics of energy storage and solar cell systems Laser based VUV pulses produced via the High Harmonic Generation process (HHG) by table-top systems enabled access to VUV and soft X-ray photon energies in the laboratory. In addition, ultrashort pulse duration downs to the attosecond scale opened new possibilities in many scientific research fields of physics and chemistry. Here our newly developed HHG-driven time- and angle- resolved PES set-up will be presented. The new machine is based on an apertureless time-of-flight electron spectrometer and a femto-second table-top laser light source. The spectrometer is equipped with supplemental pumping ports to extend the operational pressure up to 10-4 mbar range. Recently, we have studied the HHG from the gas-filled waveguide when using mixtures of two rare gases (Ar and Ne) as a nonlinear gas medium. The admixing of Ne into Ar gas can improve the generation yields of harmonics under slight phase mismatching conditions by a factor of 2. It is attributed to an improvement of the phase matching in the gas mixture. Together with our new experimental set-up, our new observation on the improved efficiency of HHG process by using two rare gas mixtures will be presented.
안녕하세요. 다음주 목요일(12월 3일) 세미나가 진행됩니다. 많은 참석 부탁드립니다. 감사합니다. ====================================== 제 목 : Self-Assembly of Nanoparticles and Functional Block-Copolymers 연 사 : 박소정 교수 (이화여자대학교) 일 시 : 2015년 12월 3일 (목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) -------------------------------------- Self-Assembly of Nanoparticles and Functional Block-Copolymers For the past few years, my group has made several important discoveries towards understanding binary self-assembly of nanoparticles and amphiphilic polymers. Based on these studies, we have developed new hybrid materials with interesting optical and magnetic properties. Furthermore, we have incorporated functional polymers such as conjugated polymers and DNA into amphiphilic structures, and showed that their properties can be drastically modified through self-assembly. These results demonstrate that amphiphilic self-assembly is a powerful tool not only for making complex nanoscale architectures but also for manipulating materials properties.
안녕하세요. 다음주 목요일(11월 26일) 세미나가 진행됩니다. 많은 참석 부탁드립니다. 감사합니다. ====================================== 제 목 : Enantioselective Construction of α-Quaternary Cyclic Carbonyl Compounds by Catalytic Asymmetric Allylic Alkylation 연 사 : 김지민 교수 (전남대학교) 일 시 : 2015년 11월 26일 (목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) -------------------------------------- Enantioselective Construction of α-Quaternary Cyclic Carbonyl Compounds by Catalytic Asymmetric Allylic Alkylation The asymmetric construction of quaternary stereocenters is a topic of great interest in the organic chemistry community. Among the available methods that afford this motif, palladium-catalyzed decarboxylative allylic alkylation has proven particularly effective and, over the last decade, Stoltz group has pursued this strategy employing chiral phosphinooxazoline (PHOX) ligands. Recently, the group disclosed the highly enantioselective palladium-catalyzed decarboxylative allylic alkylation of readily available lactams and imides to form a number of 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related N-heterocyclic compounds. In addition, cyclobutanones were successfully implemented in the enantioselective allylic alkylation serving synthetic building blocks to access a variety of enantioenriched derivative compounds. In this seminar, the palladium-catalyzed asymmetric allylic alkylations in lactams, cyclic imides, and small rings such as cyclobutanones will be discussed. References 1. C. M. Reeves, C. Eidamshaus, J. Kim, B. M. Stoltz, “Enantioselective Construction of a-Quaternary Cyclobutanones by Catalytic Asymmetric Allylic Alkylation” Angew. Chem. Int. Ed. 2013, 52, 6718. 2. N. B. Bennett, D. C. Duquette, J. Kim, W.-B. Liu, A. N. Marziale, D. C. Behenna, S. C. Virgil, B. M. Stoltz, “Expanding Insight into Asymmetric Palladium-Catalyzed Allylic Alkylation of N-Heterocyclic Molecules and Cyclic Ketones” Chem. Eur. J.. 2013, 19, 4414. 3. D. C. Behenna, Y. Liu, T. Yurino, J. Kim, D. E. White, S. C. Virgil, B. M. Stoltz, “Palladium-Catalyzed Decarboxylative Allylic Alkylation of Lactams: Enantioselective Construction of Quaternary N-Heterocycles“ Nature Chem. 2012, 4, 130.
안녕하세요. 다음주 목요일(11월 19일) 세미나가 진행됩니다. 많은 참석 부탁드립니다. 감사합니다. ====================================== 제 목 : Making Small Molecules/Large Molecules, It’s all Syntheses 연 사 : 김정곤 교수 (전북대학교) 일 시 : 2015년 11월 19일 (목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) -------------------------------------- Making Small Molecules/Large Molecules, It’s all Syntheses 1. Mechanism Guided Development of Robust C-H Amination. 2. Metal-free Hydrosilylation Polymerization In this seminar, two examples of organic and polymer syntheses based on catalysis are presented. In the first half, a mechanistic study driven development of highly active Rh(III) catalyzed C-H amination will be presented. The clear identification of a rate control factor on Cp*Rh(III) catalyzed amidation allowed us to develop a new type of amidating reagents. The new amidating reagent, 1,4,2-dioxazol-5-one is not only reactive but also has many favorable features of broad synthetic scope, safe operations, and scalability. The whole development process of the mechanistic investigation, finding new amino source, and scale-up study will be discussed. In the second half, the new route to polycarbosilanes using a non-metal catalyst is presented. Unique catalytic behaviors of boranes, especially B(C6F5)3, are of special interest. Its high and versatile reactivity has widely applied to areas ranging from hydrosilylation and reduction of simple substrates to biomass conversion into valuable hydrocarbons. Along with many interesting reactions and applications, making or manipulation of macromolecules by boranes is highly anticipated to bring new structures and properties. We recently showcased it by the first example of metal-free hydrosilylation polymerization between dienes and disilanes by B(C6F5)3, which successfully replaced precious transition-metal-based systems. Under the easy-to-handle and mild conditions, various combinations of dienes and disilanes produced polycarbosilanes with a broad range of structures and properties. Their distinctive reactivity and selectivity are discussed herein.  Park, Y.; Park, K. T.; Kim, J. G.*; Chang, S.* J. Am. Chem. Soc. 2015, 137, 4534.  Kim, D. W.; Joung, S.; Kim, J. G.*; Chang, S.* Angew. Chem. Int. Ed. 2015, Early View.
안녕하세요. 다음주 목요일(11월 12일) 세미나가 진행됩니다. 많은 참석 부탁드립니다. 감사합니다. ====================================== 제 목 : Total Synthesis of Inostamycin A 연 사 : 강성호 교수 (KAIST) 일 시 : 2015년 11월 12일 (목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) -------------------------------------- Total Synthesis of Inostamycin A Inostamycin A has been isolated from the culture broth of a microorganism pertaining to the genus Streptomyces sp. MH816-AF15.1 In the isolation process, inostamycins B and C have also been found together. Their structures were assigned by NMR spectroscopy and later inostamycin A was confirmed by X-ray crystallography of its sodium salt. While inostamycin A has ethyl group at C2, inostamycin B is one-carbon less homolog with methyl substituent instead of the ethyl and inostamycin C corresponds to decarboxylated inostamycin A. Inosamycin A sodium salt is folded around the sodium ion coordinated with its two carboxyl oxygens, two hydroxyl oxygens at C9 and C17, carbonyl oxygen at C11, and ether oxygen between C13 and C16. The folding conformation is believed to be responsible for its various potent physiological properties as an ionophoric polyether antibiotic. Inostamycin A displays inhibitory activity against phosphatidyl inositol turnover and inositol transferase to prevent cell proliferation and transformation, antibacterial activity against Gram-positive bacteria, anti-HIV activity, and reversing effect on multidrug resistance in cancer cells. It also potentiates paclitaxel cytotoxicity, and induces arrest of cell growth at G1 and apoptosis in human small cell lung carcinoma Ms-1 cells.2Intrigued by its structural complexity and promising biological activities, we have been engaged in synthetic studies on inostamycin A. In this seminar, we present the first total synthesis of the natural product. References 1. M. Imoto, K. Umezawa, Y. Takahashi, H. Naganawa, Y. Iitaka, H. Nakamura, Y. Koizumi, Y. Sasaki, M. Hamada, T. Sawa, T. Takeuchi, J. Nat. Prod. 1990, 53, 8252. 2. M. Kawatani, M. Uchi, S. Simizu, H. Osada, M. Imoto, Exp. Cell Res. 2003, 286, 57.
안녕하세요. 이번주 목요일(10월 29일) 세미나가 진행됩니다. 많은 참석 부탁드립니다.감사합니다. ====================================== 제 목 : Therapeutic siRNAs for Human Disease 연 사 : Muthiah Manoharan, Ph.D (Alnylam Pharmaceuticals) 일 시 : 2015년 10월 29일 (목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) -------------------------------------- Therapeutic siRNAs for Human Disease Synthetic small interfering RNAs (siRNAs) act as therapeutic agents through the RNA interference (RNAi) pathway and are specific and potent inhibitors of gene expression. These agents may be designed to target disease pathways previously considered “undruggable”. Numerous proof-of-concept studies both in animal models of human disease and in clinical trials demonstrate the broad potential and therapeutic value of RNAi therapeutics. The major challenge for the successful development of systemically delivered RNAi therapeutics had been the efficient delivery into organs or tissues and cells of interest to elicit RNAi mediated knockdown of faulty genes and effective translation of these approaches into clinic. At Alnylam Pharmaceuticals, we have developed chemical modifications of siRNAs to provide them with “drug-like” properties. Furthermore, efficient liver delivery approaches have been developed and clinical trials are advancing with RNAi therapeutics formulated in lipid nanoparticles (LNPs) for intravenous administration. More recently, systemic delivery of therapeutic siRNAs to liver hepatocytes by subcutaneous administration has been achieved by conjugating chemically modified siRNAs with multivalent N-acetylgalactosamine (GalNAc) residues that are recognized by the asialoglycoprotein receptor (ASGPR). siRNA-GalNAc conjugates efficiently target and silence disease-causing genes produced in liver hepatocytes. Using this conjugation platform, Alnylam is advancing several RNAi agents specific for liver targets through pre-clinical and clinical development to address diseases with highly unmet medical need. Our progress with the chemistry of siRNAs, their conjugates and applications in several therapeutic areas will be presented.