안녕하세요. 다음주 정규세미나는 목요일(12월 11일) 4시 30분부터 330226호에서 더블헤더로 진행됩니다. 많은 참석 부탁드립니다. 감사합니다. ========================= 정규세미나1. 제 목 : Molecular basis of unexpected enantioselective resolutions of aminoalcohols by lipase and Development of novel Enzyme from high-throughput screening of metagenomic library 연 사 : 이혁 박사(한국화학연구원) 일 시 : 2014년 12월 11일(목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) ------------------------- Molecular basis of unexpected enantioselective resolutions of aminoalcohols by lipase and Development of novel Enzyme from high-throughput screening of metagenomic library 1) Lipases Lipases (EC 220.127.116.11) are one of the most widely used biocatalysts in the fields of academic and industrial research because of their high levels of thermal and chemical stability. Most lipases resolve secondary alcohols in accordance with the “Kazlauskas rule” to give the R-enantiomer. In a similar manner toother lipases, Candida rugosa lipase (CRL) exhibits R-enantioselectivity towards2-heptanol, although the enantiomeric ratio (E)is low (E = 1.6). However, it has been observed unexpected enantioselectivity (i.e., S-enantioselectivity) (E = 58)of CRL towards N-Boc-4-aminobutan-2-ol, which has asimilar chain length to 2-heptanol. To develop a deeper understanding of themolecular basis for this unusual enantioselectivity, we have conducted a series of molecular modeling and substrate engineering experiments. The results of thesecomputational and experimental analyses indicated that a hydrogen bond between the Ser450 residue and the nitrogen atom of the carbamate group is critical to stabilize the transition state of the S-enantiomer. 2) Hab Mutase We have established a simple and efficient high-throughput screening (HTS) system to identify novel isomerization activity for aromatic compounds from soil metagenomic libraries. Based on this HTS approach, we have discovered and characterized a novel enzyme among 740,000 clones in metagenomic libraries. Then we attempted to develop a novel biotransformation reaction for organic synthesis. This enzyme was overexpressed in E. coli and tested for a biotransformation reaction in various reaction conditions for an optimization. The combination of reduction and isomerization was designed for an easy use of this reaction, and we prepared whole E. coli cell biocatalyst having dual activity. Using this biocatalyst, multi-step reaction with diverse aromatic compounds was successfully carried out to give rise to good yields. I will discuss the whole process from finding a novel enzyme to developing a new biotransformation. ========================= 정규세미나2. 제 목 : EGFR Inhibitors for Lung Cancer 연 사 : 이광호 박사(한국화학연구원) 일 시 : 2014년 12월 11일(목) 오후 5시 30분 장 소 : 화학관 세미나실 (330226호실) ------------------------- EGFR Inhibitors for Lung Cancer Erlotinib (Tarceva) & Gefitinib (Iressa) are currently in clinic use as epidermal growth factor receptor (EGFR) kinase inhibitors for non-small-cell lung cancer (NSCLC). However, their clinical efficacy is limited by both their mechanism-based toxicity and the development of drug-resistance mutations, including the gatekeeper T790M mutation. Unlike their quinazoline-based core scaffold, a new pyrimidine-based irreversible inhibitor has been identified for the EGFR gatekeeper T790M mutant specific activities. These pyrimidine-based EGFR inhibitors may provide improved therapeutic window and more effective clinical treatment for NSCLC patients.
안녕하세요. 다음주 정규세미나는 목요일(11월 27일) 4시 30분부터 330226호에서 더블헤더로 진행됩니다. 많은 참석 부탁드립니다. 감사합니다. ========================= 정규세미나1. 제 목 : Stereodefined N,O- and O,O-acetals: Synthesis and Application 연 사 : 이영호 교수(POSTECH) 일 시 : 2014년 11월 27일(목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) ------------------------- Stereodefined N,O- and O,O-acetals: Synthesis and Application Developing new methodologies that can introduce molecular diversity with high chemical efficiency in a highly controlled manner represents a primary goal in synthetic organic chemistry. Due to their high reactivity and chemoselectivity, organometal catalysts may play a unique role. In this presentation, our achievements on the use of stereodefined allylic N,O-acetals and O,O-acetals as a key moiety. This unstable functional group was efficiently synthesized by the unprecedented Pd-catalyzed asymmetric hydroamination of allenes. Various examples on the aza- and oxacycle synthesis will be also introduced, which illustrate the use of these stereodefined N,O-acetals as a stereodiversity-generating element. This new synthetic method should be highly useful for both the target-oriented and the diversity-oriented synthesis of bioactive natural products and analogues. References: 1. Kim, H.; Lim, W.; Im, D.; Kim, D.; Rhee, Y. H. Angew. Chem. Int., Ed. 2012,51, 12055. 2. Kim, H.; Rhee, Y. H. J. Am. Chem. Soc. 2012, 134, 4011. 3. Lee, J.; Gupta, S.; Jeong, W.; Rhee, Y. H.; Park, J. W. Angew. Chem. Int., Ed. 2012,51, 10851. 4. Kang, S.; Kim, D.-g.; Rhee, Y. H, Chem. Eur-J.2014, in press. 5. Lim, W.;; Kim, J.; Rhee, Y. H, J. Am. Chem. Soc. 2014, 136, 13618. ========================= 정규세미나2. 제 목 : Iridium-catalyzed Borylation of Secondary C-H bonds Directed By a Hydrosilyl Group 연 사 : 조승환 교수(POSTECH) 일 시 : 2014년 11월 27일(목) 오후 5시 30분 장 소 : 화학관 세미나실 (330226호실) ------------------------- Iridium-catalyzed Borylation of Secondary C-H bonds Directed By a Hydrosilyl Group Keywords C-H functionalization, borylation, Iridium Iridium-catalyzed functionalization of C‒H bonds with bis(pinacolato)diboron (B2pin2) has become a practical method for the direct formation of boronate esters. Significant progress has been made on the borylation of sp2 C−H bonds, but the borylation of sp3 C‒H bonds is less developed. Compared to the borylation of sp2C‒H bonds, the borylation of sp3 C‒H bonds typically requires high catalyst loadings and excess of the saturated substrates. The regioselectivity of the borylation of sp3 C‒H bonds strongly favors reaction at primary C‒H bonds, making the functionalization of secondary C‒H bonds challenging. In this seminar, I will present a series of catalytic reactions that convert secondary sp3 C-H bonds of alkyl groups to C-B bonds. These reactions occur through metal-boryl complexes and metal-silyl complexes. This presentation will also include information on the properties of these complexes that lead to catalytic reactions and information on the properties and reactions of the organoboron product.
안녕하세요. 정규세미나는 11월 6일 4시부터 더블헤더로 두 건이 개최됩니다. 많은 참석 부탁드립니다.감사합니다. ========================= 정규세미나1. 제 목 : Chasing Phosphohistidine, “Dark Matter” in the Phosphoproteome 연 사 : 기정민 교수(UNIST) 일 시 : 2014년 11월 6일(목) 오후 4시 장 소 : 화학관 세미나실 (330226호실) ------------------------- Chasing Phosphohistidine, “Dark Matter” in the Phosphoproteome Jung-Min Kee Department of Chemistry, UNIST, 50 UNIST-gil, Ulsan 689-798, Korea My research program in chemical biology is aimed at driving innovations in biology and medicine by utilizing synthetic protein chemistry. I will discuss my recent work on phosphohistidine (pHis), an unstable protein post-translational modification (PTM). Although the importance of pHis in cell signaling and metabolism has been long recognized, the full scope and exact function of protein histidine phosphorylation is not clearly understood. It is mainly due to the chronic lack of adequate research tools to investigate the unstable PTM. We provided first glimpse at this “dark matter” in the phosphoproteome through the development of stable phosphohistidine (pHis) analogs and specific antibodies towards pHis-containing proteins. The antibodies enabled the first selective detection and isolation of pHis proteins from native cell lysates. The phosphoproteomic workflow for pHis was also developed by synergistic combination of immunoenrichment and bioinformatic tools, thereby opening new opportunities. ========================= 정규세미나2. 제 목 : A Catalytic Enantioselective Glycolate Aldol Reaction via Lewis Base Activation of Lewis Acids and A General Enantioselective Approach to the Chemical Synthesis of the Chlorosulfolipids 연 사 : 정원진 교수(GIST) 일 시 : 2014년 11월 6일(목) 오후 5시 장 소 : 화학관 세미나실 (330226호실) ------------------------- A Catalytic Enantioselective Glycolate Aldol Reaction via Lewis Base Activation of Lewis Acids and A General Enantioselective Approach to the Chemical Synthesis of the Chlorosulfolipids Won-jin Chung Department of Chemistry, GIST, Gwangju, Korea Part 1. A general, efficient, Lewis-base catalyzed enantioselective addition of glycolate-derived silyl ketene acetals to a wide range of aldehydes will be presented. Both syn- and anti-diastereomers are accessible without changing the catalyst or controlling the geometry of the silyl ketene acetal. Simple modification of the size of alkyl groups on the silyl ketene acetal is sufficient to reverse the stereochemical course of the addition. The observed diastereoselectivity and reactivity could be rationalized by the analysis of six open transition state structures with the aid of computational analysis. Part 2. A concise and general approach has been developed for the enantioselective synthesis of three structurally related chlorosulfolipids. Key advances include highly stereocontrolled additions to a,b-dichloroaldehydes, kinetic resolution of complex chlorinated vinyl epoxide intermediates, and Z-selective alkene cross metathesis of cis-vinyl epoxides. This strategy facilitated the synthesis of enantioenriched danicalipin A, mytilipin A, and malhamensilipin A in nine, eight, and eleven steps, respectively. References 1. Chung, W.-j.; Carlson, J. S.; Vanderwal, C. D. J. Org. Chem. 2014, 79, 2226–2241. 2. Chung, W.-j.; Vanderwal, C. D. Acc. Chem. Res. 2014, 47, 718–728. 3. Chung, W.-j.; Carlson, J. S.; Bedke, D. K.; Vanderwal, C. D. Angew. Chem. Int. Ed. 2013, 52, 10052–10055. 4. Denmark, S. E.; Chung, W.-j. J. Org. Chem. 2008, 73, 4582–4595. 5. Denmark, S. E.; Chung, W.-j. Angew. Chem. Int. Ed. 2008, 47, 1890–1892.
안녕하세요. 11월 4일 1층 330118호에서 세미나가 개최됩니다. 많은 참석 부탁드립니다. 감사합니다. ================================================== 세미나2. 제 목 : A Journey Towards Ligand-Enabled Sterically Hindered Cross-Coupling Reactions 연 사 : Fuk Yee (Michael) KWONG (The Hong Kong Polytechnic University) 일 시 : 2014년 11월 4일 (화) 오후 4시 30분 장 소 : 화학관 1층 첨단강의실 (330118호실) -------------------------------------------------- A Journey Towards Ligand-Enabled Sterically Hindered Cross-Coupling Reactions Catalytic cross-coupling process has emerged as one of the most straightforward and widespread used protocols for scientists to produce chemical modifications for assembling structurally unprecedented, yet materially and pharmaceutically attractive compounds. Indeed, these methods have revolutionized the way chemists to perform complex organic synthesis. At the center of these synthetic technologies, catalyst development which allow selective bondcleavage/-construction using relatively unreactive, yet rich-feedstock in nature components would be highly attractive. Thus, catalyst exploration and development is particularly central to contemporary catalysis research for innovative organic synthesis.
안녕하세요. 세미나 공지드립니다. 11월 3일 330226호에서 세미나가 개최됩니다.많은 참석 부탁드립니다. 감사합니다. ================================================== 세미나1. 제 목 : Asymmetric hetero-Michael reaction of α,β-unsaturated carboxylic acid derivatives 연 사 : Yoshiji Takemoto (Graduate School of Pharmaceutical Sciences, Kyoto University) 일 시 : 2014년 11월 3일 (월) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) -------------------------------------------------- Asymmetric hetero-Michael reaction of α,β-unsaturatedcarboxylic acid derivatives Chiral oxygen-containing heterocycles such as isoxazolines, isoxazolidines, chromans, and dihydrobenzofurans can be found in numerous natural products and biologically active compounds. O-Heterocycles bearing amide moiety, in particular, such as roxifiban and erythrococcamide, exhibit pharmaceutically important activities, and the related carboxylic acids, such as acivicin and raxofelast, have been used as biological tools for drug discovery.Significant efforts have been focused on development of synthetic methods capable of providing facile access to these materials, but no successful reactions with unsaturated amides and carboxylic acids have been reported. Bifunctional hydrogen bond (HB)-donor organocatalysts have now come to represent a particularly promising approach to accomplishhighly enantioselective reactions, although there is still a strong drive to improve upon their catalytic activities and expand the scope of applicable reactions. We envisaged that improvements to the HB-donating ability could activate the poorly reactive Michael acceptor, and that this would be more important for an effective cyclization than increasing the basicityof the catalyst to activate the O-nucleophile. In the lecture, we report the asymmetric intramolecular oxa-Michael (AIOM) reaction of unactivated α,β-unsaturated amides and esters using powerful HB-donor organocatalysts.1)Furthermore, the products obtained from this reaction have been used for the straightforwardasymmetric synthesis of several natural products and biologically important compounds. We will also describe a new synthetic method for the AIOM reaction of α,β-unsaturated carboxylic acids using a dual arylboronic acid-aminothiourea catalytic system. We found that aminoboronic acid could be used to facilitate the intramolecular aza- and oxa-Michael reactions of α,β-unsaturated carboxylic acids. In addition, the combination of an arylboronic acid with a chiral aminothiourea provided the desired heterocycles in high yields and ee’s.2)The overall utility of this dual catalytic system was demonstrated by a one-pot enantioselective synthesis of (+)-erythrococcamide B, which proceeded via sequential Michael and amidation reactions.
안녕하세요. 다음주 월요일(10월 13일)에 세미나가 개최됩니다. 이번 세미나는 1층 330126호에서 진행됩니다. 많은 참석 부탁드립니다.감사합니다. ========================= 제 목 : Three-Membered Rings and Triple Bonds as Ideal Starting Materials for Domino Cascades 연 사 : Prof. Daniel B. Werz (Institute of Organic Chemistry, Department of Life Sciences, Technische Universität Braunschweig) 일 시 : 2014년 10월 13일 (월) 오후 4시 30분 장 소 : 화학관 1층 첨단강의실 (330126호실) ------------------------- Three-Membered Rings and Triple Bonds as Ideal Starting Materials for Domino Cascades Cyclopropanes as well as carbon-carbon triple bonds are systems being high in energy. Therefore, both moieties are ideally suited for a cascade of consecutive reactions (domino reactions). In a first part, domino reactions based on ring-enlargement reactions of donor-acceptor-substituted cyclopropanes are discussed. Aldehyde, ketimines and thioketones are utilized as acceptors whereas ether moieties serve as donor.A rearrangement leads to the respective five-membered rings which tend to eliminate water. As a result, aromatic systems are formed.Depending on the substrate domino cascades are initiated which are able to transform the biscyclopropane derivative 1 in one step into the corresponding quaterpyrrol 2. In a second part, Pd-catalyzed domino reactions starting with triple bonds attached to carbohydrate derivatives 4 are reported to construct a variety of chroman- and isochroman-type structures such as 5. Such domino sequences are also employed to a variety of other processes leading to complex scaffolds in a facile and efficient fashion. References  H.-U. Reißig, R. Zimmer, Chem. Rev. 2003, 103, 1151-1196.  a) T. F. Schneider, J. Kaschel, B. Dittrich, D. B. Werz, Org. Lett. 2009, 11, 2317-2320; b) T. F. Schneider, J. Kaschel, S. I. Awan, B. Dittrich, D. B. Werz, Chem. Eur. J. 2010, 16, 11276-11288; c) J. Kaschel, T. F. Schneider, D. Kratzert, D. Stalke, D. B. Werz, Angew. Chem. Int. Ed. 2012, 51, 11153-11156. d) J. Kaschel, C. D. Schmidt, M. Mumby, D. Kratzert, D. Stalke, D. B. Werz, Chem. Commun. 2013, 49, 4403-4405.  a) M. Leibeling, D. C. Koester, M. Pawliczek, S. C. Schild, D. B. Werz, Nature Chem. Biol. 2010,6, 199-201; b) M. Leibeling, B. Milde, D. Kratzert, D. Stalke, D. B. Werz, Chem. Eur. J. 2011, 17, 9888-9892; c) M. Leibeling, D. B. Werz, Chem. Eur. J. 2012, 18, 6138-6141; d) M. Leibeling, M. Pawliczek, D. Kratzert, D. Stalke, D. B. Werz, Org. Lett. 2012, 14, 346-349.
이번주 금요일(9월 26일)에 세미나가 개최됩니다. 많은 참석 부탁드립니다.감사합니다. ========================= 제 목 : Process Development of PI3Kβ-Sparing Inhibitor GDC-0032(Taselisib) 연 사 : TRAVIS P. REMARCHUK, PH.D.(Genentech Inc, Small Molecule Process Chemistry) 일 시 : 2014년 9월 26일 (금) 오후 4시 30분 장 소 : 화학관 1층 첨단강의실 (330126호실) ------------------------- Process Development of PI3Kβ-Sparing Inhibitor GDC-0032(Taselisib) Genentech Inc, Small Molecule Process Chemistry1 DNA Way, South San Francisco, CA 94080, USA Abstract: GDC-0032 is an orally dministrated potent PI3K kinase inhibitor that was discovered at Genentech and currently in PhI clinical trials for the treatment of cancer. In this presentation, the evolution of the process chemistry from the medicinal chemistry route up to the current manufacturing route used to produce GDC-0032 on multikilogram scale will be discussed. Multiple routes to the key starting materials as well as a more efficient convergent end-game synthesis to the API will be highlighted.
9월 11일 목요일에 세미나가 개최됩니다. 많은 참석 부탁드립니다.감사합니다. ========================= 제 목 : Nanostructured Thermoelectric Materials 연 사 : Prof.HNG Huey Hoon(Nanyang Technological University) 일 시 : 2014년 9월 11일 (목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) ------------------------- Nanostructured Thermoelectric Materials It is known that of all the primary energy we harness and use, only 30% is translated into useful work. A staggering 70% is wasted as dissipated heat during energy conversion, transportation and storage. This huge loss is itself a source of recyclable energy. If the waste heat leakage can be minimized by having the heat harnessed, stored and reused, the additional available energy can be huge. Thermoelectric (TE) devices, which can directly convert heat into electricity or vice versa, could play an important role in the energy market. TE devices can be potentially used as power generators, heat pumps, coolers and thermal sensors, which make them a unique energy harvesting and heat management system. For example, in Singapore, 42% of residential electricity is used for cooling (air conditioners), which are expected to grow at least 10% per year over the next decades. This percentage would be dramatically decreased if high-efficiency TE devices are developed to replace the traditional cooling system and realize the on-demand cooling in our daily lives (i.e. in the case of residential cooling, we can choose to only cool the chair or bed instead of the whole room). Till now, TE technology is too inefficient to be cost-effective for practical applications. Nevertheless, modern synthesis and characterization technologies are bringing TE research into a new era. In fact, the TE research area has become more promising and exciting in recent years as seen from the market forecasts for TE energy harvesters, and many companies such as BMW, have invested in TE technology. One of our research focuses is use nanostructuring to improve the TE performance of both conventional and new materials, which allows further optimization and scaling to broaden the application of TE devices. In this talk, I will focus on the various nanostructuring approaches that our group in MSE/NTU has considered to improve the performance and efficiency of various TE materials systems. I was also report on the feasibility of fabricating thin film TE device using inkjet printing, which opens up the possibility of low cost manufacturing opportunity.
다음주 목요일(8월 14일)에 특별세미나가 개최됩니다.
많은 참석 부탁드립니다.감사합니다.
제 목 : PERFORMANCE OF AMINE-RICH PLASMA POLYMERS IN BIOSENSING AND TISSUE ENGINEERING
연 사 : Prof. Lenka Zajickova(Central European Institute of Technology - CEITEC, Masaryk University, Brno, Czech Republic/Faculty of Science, Masaryk University, Brno, Czech Republic)
일 시 : 2014년 8월 14일 (목) 오후 4시 30분
장 소 : 화학관 세미나실 (330226호실)
pERFORMANCE OF AMINE-RICH PLASMA POLYMERS IN BIOSENSING AND TISSUE ENGINEERING
Lenka Zajíčková1,2, Anton Manakhov1, Marek Eliáš1,2, Petr Skládal1,2, David Nečas1,2,
Jan Čechal3, Josef Polčák3
1 Central European Institute of Technology - CEITEC, Masaryk University, Brno, Czech Republic
2 Faculty of Science, Masaryk University, Brno, Czech Republic
3 Central European Institute of Technology - CEITEC, Brno University of Technology, Brno, Czech Republic
The bio-applications of amine thin films, such as a biomolecule immobilization, biosensors or a cell adhesion enhancement require good layer stability in water. However, an improved film stability achieved by increased polymer cross-linking results in lower density of amine groups for typical allylamine or ammonia/ethylene plasma polymerization process. Cyclopropylamine (CPA) is a promising non-toxic monomer recently used for the deposition of amine-rich thin films. A relatively good water stability reported for CPA plasma polymers was promising for the bio-applications but these studies were not carried out so far.
In this work, the electrospun polycaprolactone (PCL) micro/nanofibers with the mean thickness of 1.2 ± 0.4 µm and a pore size of 8 ± 2 µm and cell cultivation dishes were coated by amine-rich thin films using low pressure capacitively coupled plasma polymerization of CPA in continuous wave and pulsed mode. In pulsed discharges the film exhibited 7 at.% of amine groups and only 1 % of the thickness was lost after immersion of in water for 216 hours. The deposition of this coating improved the cell adhesion and proliferation, as the number of mouse myoblasts grown on the substrate surface during 1 day of cultivation increased by a factor of five after deposition of CPA plasma polymer compared to the uncoated substrate.
Additionally, CPA plasma polymerization was employed to deposit stable amine thin films on the surface of quartz crystal microbalance (QCM) biosensors. The antibody specific to human serum albumin (anti-HSA) was attached to the QCM surface via cross-linkage obtained by intermediate reaction with glutaraldehyde. All steps of the bio-immobilization were studied by X-ray photoelectron and infrared spectroscopy to characterize surface and layer chemistry. The immunosensor specificity towards the HSA antigen was confirmed by the flow test for three QCM sensors which preparation started with CPA plasma polymers of different thicknesses: 20, 100 and 350 nm. The strongest response to the HSA antigen was observed for the thinnest CPA plasma polymer film and the sensor sensitivity was in this case better than for the previously reported QCM sensors functionalized by the thiol-based self-assembled monolayer.
이번주 목요일(7월 24일)에 특별세미나가 개최됩니다. 많은 참석 부탁드립니다.감사합니다. ========================= 제 목 : Organocascade reactions and synergistic c atalysis: two open gates for the synthesis of complex scaffolds 연 사 : Prof. Ramon Rios(University of Southampton, UK) 일 시 : 2014년 7월 24일 (목) 오후 4시 30분 장 소 : 화학관 세미나실 (330226호실) ------------------------- Organocascade reactions and synergistic c atalysis : two open gates for the synthesis of complex scaffolds Prof. Ramon Rios University of Southampton, UK Abstract: The synthesis of complex scaffolds is one of the major goals for synthetic chemists. In our research group we are working in the development of new organocascade reactions and in synergistic catalysis to afford new 3D-scaffolds. Several organocascade reactions have been developed in our research group to synthesize valuable compounds in high yields and ee, on the other hand Synergistic catalysis, in which two catalytic cycles involving two separate catalysts work in concerted fashion to create a single new bond, has emerged as a powerful approach for the development of new reactions. Here in we will report our last efforts in this fields.