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dc.description.abstract본 연구에서는 dual SNRI (Serotonin-Norepninephrine Reuptake Inhibitor)로 기능할 수 있는 (1S,2R)-1-(methyl(phenyl)amino)-3-(methylamino)-1-phenylpropan-2-ol을 합성하고자 하였다. 목표 물질을 거울상 이성체적으로 순수하게 합성하기 위해, one-pot reaction을 합성 전략의 중요한 방법으로 사용하는 것을 계획하였다. One-pot reaction은 실험실 수준에서의 유기화학에서 green chemistry를 달성하기 위한 방법 중 하나로 사용되는데, 환경에 해롭고 휘발성이 강한 물질들을 사용하는 양을 줄이는 것이 대표적이다. 본 연구에서는 각각 다른 2가지의 one-pot reaction을 도입한 2개의 합성 전략을 연구하였다. 첫 번째 합성 전략은 2가지의 다른 친핵체를 순차적으로 사용하는 one-pot reaction을 도입하였다. 이때, 부산물이 생성될 수 있기 때문에 첫 번째 친핵체를 정확히 1 당량 사용하는 것이 매우 중요했다. 연구 결과, 첫 번째 친핵체를 1 당량만 사용하면서도 one-pot reaction을 성공시킬 수 있었고, 최종적으로 목표 물질을 합성할 수 있었다. 두 번째 합성 전략은 첫 번째 합성 전략이 가지고 있는 효율성의 문제를 해결하기 위해 제안 되었다. 따라서, 이번에는 한가지 친핵체만 사용하는 one-pot reaction을 합성 전략에 도입하였다. 이때에는 부산물과 관련된 문제가 발생하지 않기 때문에 사용되는 친핵체의 양은 중요한 문제점이 아니었다. 과량의 친핵체를 사용한 결과, one-pot reaction에 걸리는 반응 시간이 첫 번째 합성 전략의 one-pot reaction에 비해 현저히 줄어들게 되었다. 두 번째 합성 전략에서의 또 다른 중요점은 두 개의 같은 작용기 간의 선택성이었다. 연구 결과, reduction과 protection을 따로 진행하는 것보다 한꺼번에 진행하는 것이 두 작용기 사이의 선택성을 더 높여준다는 것을 알게 되었다. 두 번째 합성 전략은 수율의 문제 때문에 완결되지 못했다. 추가적인 연구가 더 진행된다면, 두 번째 합성 전략 또한 완결할 수 있을 것이라 생각된다.;The target molecule, (1S,2R)-1-(methyl(phenyl)amino)-3-(methylamino)-1-phenylpropan-2-ol 16 can act as a dual SNRI (Serotonin-Norepinephrine Reuptake Inhibitor) and have high selectivity between NET (Norepinephrine transporter) and SERT (Serotonin transporter). For synthesis of enantio-pure target molecule, we introduced a one-pot reaction as a key step. The use of one-pot reactions is one of the approaches to achieve green chemistry in organic chemistry on laboratory by reducing the amount of harmful, volatile materials. In this research, we tried to prepare the target molecule by two synthetic strategies to utilize one-pot reactions. The first strategy applied a single one-pot process that used two different nucleophiles in sequence. Because of the formation of a by-product, using exactly 1.0 eq of the first nucleophile was a critical issue for one-pot reaction. Finally, we found the best reaction conditions for a one-pot reaction using 1.0 eq of first nucleophile to reduce the problem of by-product formation. Synthetic strategy II was suggested because synthetic strategy I has an efficiency problem. Therefore, we suggested another synthetic strategy that includes one-pot reaction using only one nucleophile. In this case, the amount of the nucleophile was not a critical issue because the problem related to by-product can be ignored. Consequently, the reaction time of one-pot reaction was much faster than that of synthetic strategy I. After the one-pot reaction, we concentrated on the selectivity between identical functional groups differently located on the synthetic intermediate. It was found that a combination of reduction and protection showed more selectivity than the separate use of the reduction and the protection. Synthetic strategy II was not completed because of the problem related to N-arylation step. If additional research is pursed, the synthesis of the target molecule by synthetic strategy II will be completed.-
dc.description.tableofcontentsI. Introduction 1 A. Depressive Disorder 1 1. Definition of the Depressive Disorder 1 2. Antidepressants 2 a. SNRI (Serotonin-Norepinephrine Reuptake Inhibitor 2 b. Target Molecule 3 B. Green Chemistry 5 1. Definition of Green Chemistry 5 2. Green Chemistry and One-pot Reactions 5 II. Results & Discussion 7 A. Synthetic Strategy I 7 1. Synthesis of (R,S)-reboxetine 7 2. Synthetic Pathway I 9 a. Overall Scheme 9 b. Results and Discussions for Synthetic Pathway I 10 (1) Preparation of Cyclic Sulfate 4 10 (2) One-pot Reaction – Part I 10 (a) Using Catalyst 11 (b) Changing Solvents 17 (3) One-pot Reaction – Part II 20 (4) One-pot Reaction – Part III 22 (5) The Whole One-pot Reaction from Cyclic Sulfate 4 to Precursor 11 24 (6) Reduction and Mono-methylation of Precursor 11 25 B. Synthetic Strategy II 25 1. Problem of Synthetic Strategy I 25 2. Synthetic Pathway II 26 a. Overall Scheme 26 b. Results and Discussion for Synthetic Pathway II 27 (1) One-pot Reaction to Prepare Diazide Alcohol 12 27 (2) Selective Reduction and Selective Protection 31 (a) Selective Reduction 31 (b) Selective Protection 32 (c) Combination of Reduction and Protection 34 (3) N-arylation 36 (4) Remaining Challenges 37 III. Conclusion 39 IV. Experimental 40 Reference 45 Appendix 47 Abstract (in Korean) 55-
dc.format.extent2264150 bytes-
dc.publisher이화여자대학교 대학원-
dc.titleSynthetic Application of a One-pot Reaction to the Synthesis of 2-Hydroxy-1,3-diamino Compounds-
dc.typeMaster's Thesis-
dc.creator.othernameLee, Na Gum-
dc.format.pagevi, 57 p.-
dc.contributor.examinerJean Bouffard-
dc.identifier.major대학원 화학·나노과학과- 2-
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