Enantioseletive aza-Michael Reactions of Nitroolefins Using Neutral Phase-Transfer Catalysis

학위논문 (석사) -- 서울대학교 대학원 : 약학대학 약학과, 2021. 2. 박형근.Chiral 1,2-diamine (vicinal diamine) functionality is a remarkable template which displays a broad spectrum of biological activity. The 1,2-diamine conformation may be found in many important compounds including antiarrhythmic, antihypertensive, antipsychotic, analgesics, antianxiety, local anesthetics In our research, we conducted neutral phase-transfer catalytic aza-Michael reaction with tert-butyl (naphthalene-2-ylmethoxy)carbamate and trans-β-nitrostyrene for Synthesis of 2-nitro-1-phenylethan-1-amine which is Chiral 1,2-diamine precursor. We could find specific phase-transfer catalyst (C-(9) urea-substituted cinchona derivatives) that shows a high yield (93%) and high optical yield (91% ee) under neutral conditions in water-rich biphasic solvent at 0℃ (saturated cesium chloride (aq): mesitylene=3:1). This established phase-transfer catalyst was used to carry out neutral phase-transfer catalytic aza-Michael reactions with 14 nitroolefins. A Plausible mechanism for the novel Neutral Phase-Transfer Catalysis based on some interesting observations was presented in this study. When the tert-butyl(naphthalene-2-ylmethyl)carbamate and trans-β-nitrostyrene were used. we suggest that the following three interactions are involved (Ion-pair interaction, π-π interaction, Hydrogen-bonding interaction).Chiral 1,2-diamine(vicinal diamine) 화합물은 인체 내에서 항불안, 항고혈압, 진통 효과 등 다양한 활성을 갖는 의약품의 출발물질로 사용된다. 즉 Chiral 1,2 diamine은 항우울제(Mirtazapine), 항히스타민제(Epinastine), 항생제(Cefaclor) 등 다양한 합성 의약품의 골격으로도 포함되어 있어chiral building blocks로 제약 산업에서 유용하게 사용되고 있다. 본 연구에서는 chiral 1,2-diamine의 전구체로서 2-nitro-1-phenylethan-1-amine을 입체 선택적으로 합성하기 위해 tert-butyl (naphthalene-2-ylmethoxy) carbamate와 trans-β-nitrostyrene을 기질로 neutral PTC-aza-Michael reaction을 진행하였다. 반응 조건의 최적화 결과saturated cesium chloride 용액과 mesitylene으로 구성된 물-유기 이중 층 용매 조건 (w/o=3:1)에서 2,4-bis(trifluoromethyl)benzyl기가 치환된 C(9) urea-substituted cinchona derivatives상전이 촉매를 사용하여 0 ℃에서 가장 효율적으로 해당 michael adduct를 얻었다. 이상에서 확립된 최적화된 조건에서 다양한14종의nitroolefins 기질에 적용한 결과 최고 93%의 화학수율과 최고 93%의 광학수율로 aza-Michael 반응을 수행할 수 있었다. 반응 메커니즘 연구를 통하여halide 음이온을 다량 포함한 고농도의 cesium chloride 수용액을 사용함으로써 neutral 상전이 촉매 반응이 원활하게 진행되어 수율이 크게 개선된 것으로 알 수 있으며, (R)-form의 입체 선택적인 반응물이 생성되었다는 결과로부터 neutral 상전이 촉매 반응 메커니즘과 함께 기질과 촉매 간의 상호작용 (Ion-pair interaction, π-π interaction, Hydrogen-bonding interaction)에 기반한 반응 전이 상태를 제안해보았다.국문 초록 1 목 차 3 Figure 목록 5 Table 목록 6 Scheme 목록 7 Ⅰ. 서 론 8 1. 비대칭 상전이 촉매 반응 (Phase-Transfer Catalysis) 8 1-1. 비대칭 상전이 촉매 반응 개요 8 1-2. PTC 촉매 (Phase-Transfer Catalyst) 12 2. Neutral 상전이 촉매 반응 15 2-1. 상전이 촉매의 지용성 효과 17 2-2. 물의 효과 19 2-3. 염의 효과 22 3. Chiral 1,2-diamine 화합물 24 3-1. Chiral 1,2-diamine 화합물의 중요성 24 3-2. 입체선택적인 aza-Michael reaction 연구 25 Ⅱ. 본 론 29 1. trans-β-nitrostyrene의 Neutral PTC aza-Michael reaction 29 1-1. 초기 반응 조건 탐색 29 1-2. 유기 용매 탐색 32 1-3. 수용액 탐색 33 2. Neutral 상전이 촉매 최적화 35 2-1. Neutral 상전이 촉매 탐색 35 2-2. 온도 탐색 39 3. Michael acceptor 40 3-1. Michael acceptor 선정 40 3-2. Michael acceptor 탐색 41 4. Plausible mechanism과 Plausible transition state 44 Ⅲ. 결 론 46 Ⅳ. 실 험 47 Ⅴ. 참고문헌 77 Ⅵ. Abstract 80 VⅡ. 부 록 82Maste

Optimization of Sparse Matrix Chain Multiplication by using Parenthesizing method

Matrix chain multiplication is an important computational kernel used in many applications such as scientific computation, signal and image processing. In this paper, sparse matrix chain multiplication is optimized by using dynamic programming method. With the proposed method, total execution time is reduced by 33%.이 논문은 지식경제부 출연금으로 ETRI와 시스템반도체산업진흥센터에서 수행한 ITSoC 핵심설계인력양성사업과 교육과학기술부의 재원으로 한국학술진흥재단에서 수행하는 BK21 프로젝트의 지원을 받아 수행된 연구입니다

Reflection Characteristics of a Slit Caisson Breakwater with Embedded Resonant Channels

Interaction of waves and a permeable structure is an attractive subject to coastal engineer. In present study, a new concept slit caisson breakwater is proposed, which has embedded channels for fluid resonance in the channel. When the amplified flow is passing through the slit plate, the incident wave energy is dissipated by flow separations. In order to evaluate wave energy dissipation performance of the breakwater, this study has focused on the wave reflection from the breakwater by using numerical simulation and hydraulic model test. The numerical experiment was carried out by Galerkin’s finite element model based on the linear potential theory, and the hydraulic model test was performed in a two-dimensional wave flume at KIOST. Comparison of the numerical results with hydraulic model test results shows proper agreement over wide wave periods. The performance of slit caisson breakwater with the embedded resonant channels was tested with various design of the embedded channel. This breakwater has advantages compared with conventional slit wall caisson breakwater. First, the channel design to control the target wave condition is easy and applicable to long wave periods for dissipating wave energy. Second, this breakwater has structural safety of slit members because the members are not exposed to impact load at near free surface, directly. When the incident wave period and natural period of water column in the channel were matched, the considerable wave energy dissipation was occurred. From this reason, the wave load acting on the breakwater is decreased by wave energy dissipation. The wave reflection characteristics were affected by the porosity of slit plate, the channel width, and the number of channels. Therefore, this breakwater is expected to economical and efficient coastal structures.CHAPTER 1 INTRODUCTIONS 1 1.1 Research Background 1 1.2 Literature Survey 2 1.3 Research Objectives and Scope 4 CHAPTER 2 THEORETICAL FORMULATION 6 2.1 Boundary Value Problem 6 2.2 Fluid Domain 8 2.3 Energy Dissipation at Slit Plate 11 2.4 Motion of Fluid in Channel 15 CHAPTER 3 FINITE ELEMENT FORMULATION 17 3.1 Genaral 17 3.2 Discretization of Fluid Domain 17 3.2.1 Finite Element Region 20 3.2.2 Infinite Element Region 23 3.3 Formulation of the Model 26 CHAPTER 4 NUMERICAL RESULTS AND DISCUSSIONS 27 4.1 General 27 4.2 Embedded Single Case 31 4.2.1 Influence of depth of the channel inlet 31 4.2.2 Influence of the channel width 41 4.3 Embedded Multi-Channels Case 53 4.3.1 Comparison of double and single embedded channel 53 4.3.2 Comparison of triple and single embedded channel 61 4.4 Comparison with other research 69 CHAPTER 5 HYDRAULIC MODEL TEST 71 5.1 General 71 5.2 Wave Flume 71 5.3 Model Set-up 72 5.4 Experimental Analysis 78 5.4.1 Separation of Incident and Reflected Waves 78 5.4.2 Comparison of Numerical and Experiment Results 81 CHAPTER 6 CONCLUSIONS 88 6.1 Conclusions 88 6.2 Future Studies 91 REFERENCES 92 APPENDICES 9

Parallel Implementation of WFST-based Large Vocabulary Continuous Speech Recognition on Graphics Processing Units

학위논문 (석사)-- 서울대학교 대학원 : 전기. 컴퓨터공학부, 2011.2. 성원용.Maste

The Changes of electron transfer partitioning affected by light and glucose in the thylakoid membrane of cyanobacterium synechocystis sp. PCC 6803, and the study on the instructuional strategies based on the motivation types and learning strategies

학위논문(박사)--서울大學校 大學院 :科學敎育科,1996.Docto

보툴리눔 독소 주사를 위한 작은광대근과 입꼬리내림근의 임상해부학적 연구

Dept. of Dentistry/박사The zygomaticus minor muscle (Zmi) is involved with the formation of negative expressions; it raise the corner of the mouth and upper lip, then helps to curl the upper lip when showing contempt, smugness, and disdain. It also helps to deepen the nasolabial sulcus when showing sadness. Drooping of the mouth corner caused by hyperactivity of the depressor anguli oris (DAO) can also generate a sad, tired, or almost angry look in some patients. However, The details of the Zmi insertion pattern and morphology are not well described even in general anatomy textbooks and illustrations. In addition, it is difficult to inject botulinum toxin type A (BoNT) into the DAO because its medial border overlaps with the depressor labii inferioris, and its lateral border is adjacent to the risorius, zygomaticus major, and platysma muscles. The aim of this study was to clarify the morphology and insertion pattern of the Zmi, and to provide critical information for determining the safest and most effective BoNT injection site of the DAO.Fifty-four embalmed adult hemifaces (48 bilateral and 6 unilateral; 31 males, 23 females; age range, 45–48 years; mean age, 67.4 years) from 30 cadavers were used in Zmi study and forty-two hemifaces from Korean (20 hemifaces, 9 left and 11 right; mean age, 69.1 years) and Thai (22 hemifaces, 11 left and 11 right; mean age, 78.4 years) adult cadavers (in total, 20 left and 22 right; mean age, 73.9 years) were dissected for DAO study.The Zmi was classified into three types. Type A, in which the Zmi attached only to the upper lip, was observed in 63.0% (34/54) and was subdivided into two types: straight (A-1; 31.5%, 17/54) and curved (A-2; 31.5%, 17/54). Type B, in which the Zmi was attached to both the upper lip and the lateral alar region, occurred in 27.8% (15/54). In type C, there was either no or only undeveloped Zmi fibers (9.2%, 5/54). The location of the modiolus was 11.0±2.6mm laterally and 8.9±2.8mm inferiorly to the cheilion. The angle formed by the sagittal line passing through the modiolus (LV) and the line connecting the modiolus and P2 (the point which meet the lateral border of the DAO and the mandibular border) was 44.7±13.7°. The angle formed by LV and the line connecting the modiolus and the most concave point of the medial border of the DAO (LP3) was 31.8±8.5°.The present finding of Zmi fibers being attached to the alar region in many cases (27.8%) suggests that this muscle is involved in elevation of both the nose ala and upper lip. The fan-shaped area bounded by LP2, LP3, and the mandibular border is the safest and most effective injection site for DAO.ope

항EGF수용체 면역나노전달체를 이용한 표적 선택적 항암 유전자 전달

Dept. of Biomedical Laboratory Science/박사Cancer gene therapy is the treatment of cancers by transferring therapeutic genes (plasmid DNA, micro RNA or small interfering RNA) with gene delivery systems. The drawbacks of gene delivery systems in the issues of safety and transfection efficiency make their clinical applications difficult. Liposomal gene delivery systems have been considered to be relatively safer, less immunogenic and non-infectious than viral gene delivery systems. Typically, cationic liposomes have been widely utilized for in vitro and in vivo gene transfection because of easy and stable formation of liposome-DNA complexes called lipoplexes. In recent years, the liposomal gene delivery systems have been improved in terms of transfection efficiency and stability in vivo. For example, virosomes, fusogenic viral envelop proteins reconstituted in liposomal vesicles, were more effective in transfection to various cells and tissues than other conventional cationic lipoplexes. However, gene transfection efficiency of liposomal systems still needs to be further improved for clinical applications. In this study, anti-epithermal growth factor receptor (EGFR) immunonanoparticles (immunoliposomes, immunovirosomes, immunolipoplexes and immunoviroplexes) were developed for EGFR-directed gene delivery to cancer cells. The four different types of EGFR-targeted liposomal systems were finally constructed by conjugation of Cetuximab, anti-EGFR monoclonal antibody, to PEG termini on the liposomal surface. The resulting anti-EGFR antibody-conjugated immunonanoparticles were able to effectively deliver genes (pDNA and siRNA) to EGFR-positive cancer cells (A549 and SK-OV-3 cells), but not to EGFR-negative ones (MCF-7 and B16BL6). Especially, the anti-EGFR immunoviroplexes exhibited the most efficient transfection to EGFR-expressing tumor cells than the others. The anti-EGFR immunonanoparticles were able to more selectively deliver to SK-OV-3 tumors xenografted in mice than conventional cationic DMKE/Chol lipoplexes. The two different types of anticancer genes (pDNA; IL12 gene and/or salmosin gene, siRNA; vimentin siRNA and/or JAK3 siRNA) were encapsulated in anti-EGFR immunolipoplexes and anti-EGFR immunoviroplexes and then intravenously injected to the SK-OV-3 tumor-xenografted mouse model. The gene transfected mice were also treated with anti-cancer drug, doxorubicin. According to the experimental data, the anti-EGFR immunonanoparticles containing both types of anticancer genes were more effective in inhibition of tumor growth and metastasis. In addition, the combined treatment with doxorubicin was able to synergistically inhibit SK-OV-3 tumor growth in mice. Among the anti-EGFR immunononoparticles, the anti-EGFR immunoviroplexes exhibited the most efficient EGFR-specific transfection, resulting in the most effective therapeutic efficacy. This study suggests that the anti-EGFR immunonanoparticles, specially the anti-EGFR immunoviroplex formulation, would be useful as an efficient tumor-specific gene delivery system for cancer gene therapy. Also, combination of conventional chemotherapy and tumor-directed anticancer gene therapy can be an acceptable modality for anticancer therapy.ope

건설 분야 전자매뉴얼을 위한 집단지성 기반의 정보 관리 모델 구축

학위논문(석사)--서울대학교 대학원 :건축학과,2011.2. 박문서.Maste

A Study on the Glass Works for the Expansion of Interior Space

학위논문 (박사)-- 서울대학교 대학원 : 디자인학부 공예전공, 2011.2. 서도식,;정영목.Docto