35 research outputs found
Development of new olefin metathesis reactions via substrate modification: Alkyne and olefin metathesis
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Όλ¬Έ (λ°μ¬)-- μμΈλνκ΅ λνμ : ννλΆ μ κΈ°νν μ 곡, 2016. 2. μ΅νλ¦Ό.Olefin metathesis (OM) reaction is a facile reaction to synthesize various molecules through carbon-carbon double bond rearrangement. With the development of more reactive yet functional group tolerant catalysts, OM proved its usefulness and became one of the most important reaction in modern organic chemistry. Among the various olefins that can subjected to OM, alkynes have special characteristic. As OM only exchanges carbon-carbon double bonds, reaction between alkyne and metal carbene catalyst does not completely cleave carbon-carbon triple bond: instead, new metal 1,3-dienylidene is formed, which can undergo further metathesis reactions, such as enyne metathesis or conjugated polyene synthesis. This thesis will describe about the various application of OM with alkynes, from synthesis of small molecules to high-molecular-weighted conjugated polyenes.
Chapter 2 describes synthesis of multicyclic compounds through selective tandem dienyne ring-closing metathesis (RCM) reaction and Diels-Alder reaction. Dienyne RCM reaction is a useful reaction to synthesize fused bicyclic compounds, but due to the lack of catalyst selectivity between olefins with same structures, dienyne RCM reaction tend to produce two different isomers with different ring sizes. Also, product of conventional dienyne RCM reaction was restricted to the bicyclic compounds containing small or medium sized rings only. Thus, conformation of 1,3-diene functional group in bicyclic compound was fixed to s-trans conformation, thus further modification such as Diels-Alder reaction was impossible. By modifying the dienyne substrate to contain long tether to synthesize bicyclic compound comprising small (5-7 membered) and large (14-17 membered) rings, both problems could be solved. As cyclization rate of small ring and catalyst exchange rate between alkenes were significantly faster than that of large ring, single isomer could be synthesized from dienyne RCM reaction. Also, due to the flexible macrocycle chain, 1,3-diene functional group could form s-cis conformation, which could undergo Diels-Alder reaction to synthesize multicyclic compound.
Chapter 3 describes tandem ring-opening/ring-closing metathesis (RO/RCM) polymerization of monomers containing cycloalkene and alkyne. Although cycloalkenes with low ring strain and alkynes were not suitable for metathesis polymerization, mixing those two functional groups in one monomer facilitated efficient tandem RO/RCM reaction to perform ultrafast living polymerization. Living characteristic of tandem polymerization could also synthesize block copolymers. Also, 1,3-diene functional groups in the polymer backbone could undergo further modification by cycloadditionr reactions. By changing monomer structures, we found out that monomers with certain combinations of cycloalkene, alkyne, and linker group could undergo efficient polymerization, while monomers with other combinations did not. In order to increase polymerization efficiency, two strategies were proposed. Firstly, monomer structures were modified to increase intramolecular RO/RCM with enhanced Thorpe-Ingold effect, which allowed the synthesis of challenging dendronized polymer. Secondly, reaction concentration was reduced to suppress intermolecular side reactions, which could effectively polymerize monomers without structural modifications. In order to further broaden the monomer scope, monomers containing internal alkynes were also studied, and surprisingly, monomers with internal alkynes tend to undergo non-selective Ξ±- and Ξ²-addition to form two different polymer units with different ring structures. Further studies revealed that steric and electronic effects of internal alkyne substituents changed polymer unit ratio, polymerization reactivity, and even polymerization kinetics. Thorough mechanism study revealed that the rate-determining step of monomers containing certain internal alkyne was six-membered ring cyclization step via Ξ²-addition, whereas that for monomers containing other alkynes was the conventional intermolecular propagation step, as observed in other chain-growth polymerization reactions.
Last chapter describes about fast cyclopolymerization of 1,7-octadiyne derivatives. Although cyclopolymerization was effective for the synthesis of conjugated polyenes, cyclopolymerization of 1,7-octadiyne was rarely studied, due to the slow polymerization rate by slow six-membered ring cyclization rate. Although this polymerization rate could be increased by using bulky substituents in side chains, simply increasing substituent bulkiness could not effectively increase polymerization rate. Thus, we proposed two strategies to increase polymerization rate. Firstly, dimethyl substitution was introduced to Ξ±-position of side chains. This strategy effectively increased polymerization rate by enhanced Thorpe-Ingold effect, and synthesis of 50-mer polymer could be done within 1 hour, instead of previous 24 hours. However, in order to achieve controlled polymerization, reaction temperature should be decreased and polymerization time was increased to 6 hours. To solve this problem, second strategy was applied: by changing substituent position from 4,4-disubstitution to 4,5-disubstitution, polymerization rate was significantly increased, and even living polymerization with narrow PDI and well-predictable molecular weight was possible within 1 hours, and even challenging synthesis of dendronized polymer could be possible. All those polymers were analyzed by UV-Vis, NMR, and IR spectroscopy to observe polymer backbone structures, such as conjugation length of polymer and cis/trans conformation of polymer backbone.Chapter 1. Olefin metathesis reaction with alkyne 1
Brief history of olefin metathesis with alkyne 3
Thesis research 9
References 10
Chapter 2. Synthesis of fused multicyclic compound through dienyne ring-closing metathesis and Diels-Alder reaction 13
Abstract 15
Background 15
Introduction 18
Results and Discussions 19
Conclusion 35
References 36
Chapter 3. Tandem ring-opening/ring-closing metathesis polymerization 39
Abstract 41
Background 42
Part A. Tandem RO/RCM of monomers containing nitrogen linker group 45
Introduction 45
Results and Discussions 46
Conclusion 61
Part B. Strategies and deeper mechanistic study of monomers with low reactivity 62
Introduction 62
Results and Discussions 62
Conclusion 82
References 83
Chapter 4 Fast diyne cyclopolymerization of 1,7-octadiynes 87
Abstract 89
Backgrounds 89
Part A. Cyclopolymerization of 1,7-octadiynes containing dimethyl substituents in Ξ±-position of side chain 93
Introduction 93
Results and Discussions 95
Conclusion 104
Part B. Cyclopolymerization of 4,5-disubstituted 1,7-octadiyne 106
Introduction 106
Results and Discussions 107
Conclusion 120
References 120
Supporting Information 123
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Pregnancy outcomes and factors associated with cesarean section in induced labor with prostaglandin E2 pessary
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Όλ¬Έ(μμ¬)--μμΈλνκ΅ λ³΄κ±΄λνμ :보건νκ³Ό μνμ 곡,2007.Maste
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κ΅μ‘μ 곡,2020. 2. μ΄μμ.The purpose of this study is to examine the changes of bowing technique depending on the emotional expression of bowed string instrument performers and to suggest a new educational orientation in the practical teaching guidance of bowing. For this purpose, this study quantitatively analyzes articulations and bow-strokes depending on the four emotional indicators of happy, sad, relaxed, and angry of cello performers, and quantifies how accurately the intention of the performer's expression is delivered to the listener. An experiment consists mainly of performance recording and listening evaluation. First, the first experiment is a performance experiment that has examined the articulations and bow-strokes depending on the four emotional indicators of happy, sad, relaxed and angry of 14 cello performers(mean age = 25.93, SD = 2.464) who have been trained for more than 10 years. The second experiment is a listening experiment to examine how accurately the emotions expresses by the performer are perceived by 247 non-music major students(mean age = 19.90, SD = 1.618).
The results of this study are as follows. First, the results of the Experiment 1(performance recording) reveals that staccato, legato, tenuto, and accent articulations shows significant differences among the four emotional indicators. The performers generally uses staccato and accent for the high-arousal happy and angry, while they uses legato and tenuto for the low-arousal sad and relaxed Moreover, the results of the statistical significance test for valence and arousal, which are selected as the criteria for experimental stimulation, reveals that all four articulations has significant differences according to arousal; Tenuto and accent have differences according to valence, however, it is relatively insignificant compared to arousal. Second, the results of examining the ratio of bowing stroke according to the four emotional indicators demonstrates that all emotional indicators have statistically significant differences except happy and angry, sad and relaxed which corresponds to the same arousal. In the high-arousal, the performers tends to play in the dΓ©tachΓ© method using separated bows, while in the low-arousal, they tends to connect several notes and play in a slur method. Also, in order to examine visually how the above two bowing clues affect the actual acoustic difference, the study focuses on the envelope according to each emotional index. For the high-arousal, each note proceeds regularly and individual notes are disconnected. On the other hand, for the low-arousal, the distinction between attack and decay parts is not clear, which shows continuous envelope. It is also important to note that, despite controlling tempo-variables, the performers tends to be slow in sad, which is inferred by the use of fermata at the end of each bar or in the entire melody.
Next, the results of the Experiment 2-Listening Evaluation shows that respondents relatively well matches the emotions expressed by the performers, although the correct answer rate does not meet the standard suggested in the previous studies. Of the four emotions, the response to angry has the highest accuracy. A noteworthy point is the difference in the modality of the melody. In major tonality, the accuracy of response to emotion corresponding to happy and relaxed (positive valence) is high, and the response to the emotion of sad and angry (negative valence)is high in minor. Moreover, in the case of incorrect answers, the respondents tends to perceive sad and happy as relaxed in major, and in minor tonality, the percentage of happy and relaxed expressed by the performers are rather perceived as sad. This is because the modality of the melody influences the perceptions and understands of the listeners. In other words, major tonality has a strong correlation with positive valence whereas minor tonality has a strong correlation with negative valence.
This study is significant in three aspects. First, in terms of research, it is significant to examine the emotional transfer process of the performer-listener through the new bowing clue, which is different from the existing studies on the relationship between the emotional expression of the keyboard instrument performer and the musical cues. Second, in terms of performers, this study takes into account the importance of bowing by investigating the effect of bowing on the physical sound as well as its function to express and convey the feelings and emotions of the performer to listeners. Lastly, from the educational point of view, preparing a practical guidance plan emphasizing the expressive aspects of bowing based on the results of this study can ultimately suggest a new orientation of teaching and learning methods of bowing.λ³Έ μ°κ΅¬λ μ°°νμ
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It has been known that Proteinases of parasites might be closely related with their pathogenicity and cytotoxicity in terms of host-parasite relationship. The present study also aimed to elucidate whether proteinases from the lysates or secrete materials of pathogenic Naegleria fowleri and Non-pathogenic N.gruberi are related With their cytotoxic activities. Mice inoculated with 1Γ10**5 N.fowleri trophozoites showed their cumulative mortality rate of 75% during observation, While no mouse was dead in the group inoculated with same amount of trophozoites of nonpathogenic N.gruberi. Utilizing Chinese hamster ovary(CHO) cell line incubated with radioactive (51)**Cr ( (51)**Cr -labeled CHO cells), cytotoxicities of free living amoebae were assayed. Scanning electron microscopic observations of target CHO cells affected with purified cytotoxic substance of N.fowleri were also carried out.
To determine the types and electrophoretic banding patterns of proteinases, the effect of various proteinase inhibitors on the activities were examined, and found that enzymes from N.fowleri showed different patterns from N.gruberi. Cytotoxic activities determined by the release of (51)**Cr from CHO cells were significantly detected in the lysate and cultured media of N.fowleri, but very little cytotoxic activities were shown in the lysate and cultured media of N.gruberi. Rate of flow(Rf)values electrophoretic banding patterns varied between the proteinase of
lysate and the cultured media of N.fowleri, but a value of Rf 0.87 was common in both bands. Purification of proteinase in the cultured media of N.fowleriwas performed by centrifugation, ammonium sulfate fractionation, and spectra/Gel AcA 44 column chromatography. Purification was achieved up to a 23.6 fold increase in comparison with the raw materials of the intact N.fowleri cultured media and yielded about 19.9% of the total amount.
The partially purified cytotoxic substance determined by SDS-PAGE was 17,500 dalton in molecular weight and the value of Rf 0.87 was determined by gelatin containing SDS-PAGE. Enzymatic activities in the N.fowleri cultured media were examined using various proteinase inhibitors and substrates, and confirmed that
cysteine and aspartic acid residues were responsible for the cytotoxic activity.
Scanning electron microscopic findings of the CHO cell treated with partially purified cytotoxic substance of N.fowleri for 30 up to 180 minutes showed the deterioration of microvilli on the entire surface of the cell, plasma membrane blebbing and holes in the plasma membrane.
From the above findings of the biochemical and physical properties of the cytotoxic substance from N.fowleri cultured media, it is suggested that the mainly cysteine proteinase secreted from N.fowleri might damage the cell membranes of the
target cells.restrictio
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