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Enantioselective synthesis of α-alkylthio-α-alkylmalonate via phase-transfer catalytic sulfenylation
DC Field | Value | Language |
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dc.contributor.advisor | 박형근 | - |
dc.contributor.author | 김병수 | - |
dc.date.accessioned | 2017-07-19T11:21:05Z | - |
dc.date.available | 2017-07-19T11:21:05Z | - |
dc.date.issued | 2015-08 | - |
dc.identifier.other | 000000053350 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133590 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 약학과(약품제조화학전공), 2015. 8. 박형근. | - |
dc.description.abstract | Chiral α-alkylthio-α-alkylmalonate 유도체는 생물학적 활성이 있는 천연물 또는 의약품 합성에 잠재적으로 매우 중요한 중간물질이다. 현재 황을 포함하는 4차 탄소 입체 중심을 도입하기 위해서 주로 쓰는 direct sulfa-Michael addition을 비롯한 다양한 합성적인 접근법이 연구되고 있다. 그러나 sulfenylation은 기질을 합성하거나 화학 작용기를 변환하기가 어렵다는 단점이 있다. 연구를 확장하는 차원에서, 본 연구자는 상전이 촉매를 이용한 α-alkylmalonate의 비대칭적인 sulfenylation을 통해 황을 포함하는 chiral 탄소 입체 중심을 만드는 새로운 합성법을 설계하였다.
본 연구실에서는 최초로 상전이 촉매를 이용해서 malonate의 α위치에 높은 화학적 수율과 광학적 수율로 alkyl 작용기를 도입하는 방법을 보고한 바 있다. 또한 이를 이용하여 4차 탄소 입체 중심을 포함하는 여러 chiral building blocks를 합성하여 성공적으로 응용 가능성을 증명한 바 있다. 상전이 촉매 반응은 반응 조건이 상대적으로 온화하며 반응 진행 시 시약과 촉매로도 경제적이고 환경적으로 지속 가능한 물질들을 사용한다. 본 연구자는 상전이 촉매를 이용해서 α-alkylmalonate의 입체선택 sulfenylation을 성공적으로 수행하였다. (1S,2S,4S,5R)-2-((R)-(allyloxy)(6-methoxyquinolin-4?yl)methyl)-5-ethyl-1-(2,3,4?trifluorobenzyl)quinuclidin-1-ium bromide 상전이 촉매 존재 하에서 다양한 chiral 중간물질로 변환 가능한 여러 α-alkylthio-α-alkylmalonate를 최대 97%의 화학적 수율과 최대 90%의 광학적 수율로 합성하는데 성공하였다. | - |
dc.description.abstract | The chiral α-alkylthio-α-alkylmalonate derivative is one of the most potentially valuable intermediates to synthesize biologically active natural products and pharmaceuticals. There have been many synthetic approaches to construct sulfur-bearing quaternary chiral carbon centers, mostly by the direct sulfa-Michael addition. However, sulfenylation has many drawbacks in preparing substrates and modifying functional groups. To expand the scope of research, our research team designed a novel synthetic method for constructing sulfur-bearing chiral carbon centers by the asymmetric sulfenylation of α-alkylmalonates via phase-transfer catalysis.
Our research team recently reported the enantiomeric α-alkylation of malonates with high chemical yield and optical purity via phase-transfer catalysis for the first time and successfully proved its effectiveness through synthesizing various chiral building blocks bearing quaternary carbon centers using it. The phase-transfer catalysis occurs under relatively moderate conditions and its reagents and solvents are economical and environmentally sustainable. The enantioselective phase-transfer catalytic sulfenylation of α-alkylmalonate was accomplished in the presence of the phase-transfer catalyst, (1S,2S,4S,5R)-2-((R)-(allyloxy)(6-methoxyquinolin-4-yl)methyl)-5-ethyl-1-(2,3,4-trifluorobenzyl)quinuclidin-1-ium bromide, to afford the corresponding α-alkylthio-α-alkylmalonates in high chemical (up to 97%) and optical (up to 90%) yields which can be readily converted to versatile chiral intermediates. | - |
dc.description.tableofcontents | ABSTRACT 1
TABLE OF CONTENTS 2 LIST OF FIGURES 4 LIST OF TABLES 5 LIST OF SCHEMES 6 INTRODUCTION 7 1. The characteristics of malonic esters 7 2. Asymmetric phase-transfer catalysis 8 2.1. Nature of asymmetric phase-transfer catalysis 8 2.2. Cinchona- and non-cinchona-class phase-transfer catalysts (PTCs) 10 2.3. Asymmetric phase-transfer catalytic alkylations of the Schiff base 12 3. Asymmetric sulfenylations 14 RESULTS AND DISCUSSION 16 1. The design of a novel substrate for asymmetric sulfenylations 16 2. Enantioselective phase-transfer catalytic sulfenylation of the benzhydrylideneamino tert-butyl malonate 18 2.1. Optimization of phase-transfer catalytic sulfenylation 18 2.2. The enantioselective phase-transfer catalytic sulfenylations with several electrophiles 23 3. The application of α-alkylthio-α-alkylmalonates 25 CONCLUSION 26 EXPERIMENTAL SECTION 27 1. General Methods 27 1.1. Solvents and reagents 27 1.2. Chromatography 27 1.3. Spectral data 27 2. α-Alkylthio-α-alkylmalonates 29 2.1 Preparation of α-alkylmalonate substrate 29 2.2 General procedure for synthesis of N-(alkylthio)- phthalimides 34 2.3 General procedure for asymmetric phase-transfer catalytic sulfenylation 36 REFERENCES 42 국문초록 43 | - |
dc.format | application/pdf | - |
dc.format.extent | 1673778 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | enantioselective sulfenylation | - |
dc.subject | α-alkylthio-α-alkylmalonate | - |
dc.subject | asymmetric phase-transfer catalysis | - |
dc.subject.ddc | 615 | - |
dc.title | Enantioselective synthesis of α-alkylthio-α-alkylmalonate via phase-transfer catalytic sulfenylation | - |
dc.type | Thesis | - |
dc.description.degree | Master | - |
dc.citation.pages | 43 | - |
dc.contributor.affiliation | 약학대학 약학과 | - |
dc.date.awarded | 2015-08 | - |
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