DEVELOPMENT OF USEFUL SYNTHETIC METHODOLOGIES AND STRUCTURAL, BIOLOGICAL STUDY ON SOME HETEROCYCLES
- Alternative Title
- 다양한 피페리돈 유도체의 유용한 합성방법론, 구조 및 생리학적인 연구
- Abstract
- The thesis entitled “Development of Useful Synthetic Methodologies and Structural, Biological Study on Some Heterocycles” is divided into two parts. The first parts deals with development of some useful synthetic methodology for the synthesis of biologically valuable precursor while the second part deals with structural study of some diversified piperidin-4-one/oxime using single crystal XRD and 1D/2D NMR and their cytotoxicity effect on Human cervical cancer cells.
The first part is further divided into five chapters. In first part we concentrated on development of truly efficient, green, expeditious and environmentally benign methodology for the synthesis of useful precursor in the field of biology, industry, and key intermediate for the multistep synthesis. In this concern initially we focused to find best reusable catalytic system an attempt to reduce the environmental hazards associated with the conventional acid/base system. So various, heterogeneous catalysts (Lewis acid) have been prepared and screened for the synthesis of various useful precursor. In some case we found that solvent free condition is rapid, green and efficient condition for some multicomponent reactions such as, Kabachnik-Fields reaction, Betti reaction, and A3-coupling reaction for synthesis of propargylamines.
In second part we studied structural and biological studies of poly-functionalized piperidine-4-one and piperidin4-one-oxime respectively. The second part is further divided in three chapters. In first two chapters we detailed investigated the stereochemistry of non benzylated 3,5-dialkyl-2,6-diarylpiperidin-4-ones and N-benzylated 3,5-dialkyl-2,6-diarylpiperidin-4-ones using 1D/2D NMR and single crystal XRD. In continuations with previous work further we decided to convert C-4 carbonyl of of N-benzylated 3,5-dialkyl-2,6-diarylpiperidin-4-ones to respective oxime by keeping their biological importance in the field of medicinal chemistry. So in third chapter we synthesized series of novel N-benzylpiperidin-4-one oximes and evaluated for their in vitro cytotoxicity against human cervical carcinoma (HeLa) cell line using MTT assay. The all synthesized compounds were well characterized by 1D NMR as well as single-crystal XRD.
논문제목은 Development of Useful Synthetic Methodologies and Structural, Biological Study of Some Diversified Piperidone(유요한 합성법 방법 계발 과 Diversified Piperidone 의 구조와 생물학적 연구).이다. 본 논문은 두개의 부분으로 나눠진다. 첫번째 부분은 생물학적으로 유용한 합성방법을 다룬다. 다음 두번째 부분은 여러가지 piperidin-4-one/oxime를 이용한 단결정의 XRD, 1D/2D NMR 분석과 자궁암 세포의 영향에 관한연구를 다룬다
첫번째 부분은 다섯장으로 이루어진다. 생물학또는 화학산업분야에 효육적이고 친환경적인 방법을위한 다단계 합성 방법 을 소개한다. 이전의 환경적으로 위험한 산, 염기 시스템을 줄이는 시도로 재사용가능한 촉매 시스템에 집중하였다. 그래서 다양한 종류의 촉매가 사용되어 물질의 합성을 위해 많이 이용되었다. Kabachnik-Fields 반응, Betti 반응 그리고 A3-coupling 반응과 같은 solvent free condition 반응은 빠르고, 친환경적이며 효율적인 것을 찾았다.
그리고 우리가 연구한 두번째 부분은 생물학적인 구조 poly-functionalized piperidine-4-one과 piperidin4-one-oxime respectively이다. 3개의 장으로 나뉘는데 처음 2장은 non benzylated 3,5-dialkyl-2,6-diarylpiperidin-4-ones and N-benzylated 3,5-dialkyl-2,6-diarylpiperidin-4-ones 의 1D/2D NMR 분석과 single crystal XRD 분석을 통한 구조적인 연구이다. N-benzylated 3,5-dialkyl-2,6-diarylpiperidin-4-ones의 각각의 oxime은 medicinal chemistry 분야의 생물학적으로 중요하기 때문에 C-4 carbonyl 바꾸기로 결정 하였다. 그리고 3번째 장은 새로운 N-benzylpiperidin-4-one oxime의 합성과 MTT assay 분석을 통해 자궁암 세포와의 반응을 진행하였다. 합성한 모든 물질은 1D NMR뿐만아니라 single-crystal XRD분석으로 구조를 확인하였다.
- Issued Date
- 2013
- Awarded Date
- 2013. 2
- Type
- Dissertation
- Publisher
- 부경대학교
- Affiliation
- 부경대학교 대학원
- Department
- 대학원 이미지시스템공학과
- Advisor
- Yeon Tae Jeong
- Table Of Contents
- Table of Contents
Acknowledgements i
List of Abbreviations iii
English Abstract iv
Korean Abstract x
Table of contents xi
Part I: Development of useful synthetic methodologies 1
I.I Introduction 1
I.II Present work 2
I.III References 4
Chapter 1. BF3∙SiO2 is a simple and efficient Lewis acid catalyst for the one-pot synthesis of polyfunctionalized piperidin-4-ones 5
1.1. Inroduction 5
1.2. Result and Discussion 6
1.3. Experimental 11
1.3.1. Materials and methods 11
1.3.2. Preparation of silica-supported BF3 11
1.3.3. General procedure for the synthesis of 3,5-dialkyl-2,6-diarylpiperidin-4-ones (1-15) 11
1.3.4. Spectral Characterization data 12
1.4. Conclusion 16
1.5. References 17
Chapter 2. Cd(ClO4)2∙xH2O as a novel catalyst for the synthesis of α-aminophosphonates under solvent-free conditions 19
2.1. Inroduction 19
2.2. Result and Discussion 22
2.3. Experimental 25
2.3.1. General 25
2.3.2. General procedure for the preparation of α-aminophosphonates using Cd(ClO4)2 ∙xH2O 25
2.3.3. Spectral Characterization data 25
2.4. Conclusion 28
2.5. References 29
Chapter 3. An eco-sustainable green approach for the synthesis of propargylamines using LiOTf as a reusable catalyst under solvent-free condition 30
3.1. Inroduction 30
3.2. Result and Discussion 33
3.3. Experimental 39
3.3.1. Typical procedure for the A3 coupling reaction 39
3.3.2. Spectral Characterization data 39
3.4. Conclusion 40
3.5. References 41
Chapter 4. Supported copper triflate as an efficient catalytic system for the synthesis of highly functionalized 2-naphthol Mannich bases under solvent free condition 43
4.1. Inroduction 43
4.2. Result and Discussion 47
4.3. Experimental 52
4.3.1. General chemicals 52
4.3.2. Preparation of supported copper triflate 52
4.3.3. Typical procedure for the 1-(α-aminoalkyl)-2-naphthol derivatives 52
4.3.4. Spectral Characterization data 53
4.3.5. Recording of single-crystal XRD of compound 4a. 59
4.4. Conclusion 63
4.5. References 66
Chapter 5. Silica supported ceric ammonium nitrate (CAN-SiO2): Efficient catalyst for the cascade synthesis of biologically active 3-aryl-3,4-dihydro-1,2,4 benzothiadiazine-1,1-dioxides 68
5.1. Inroduction 68
5.2. Result and Discussion 70
5.3. Experimental 77
5.3.1. General chemical and Methods 77
5.3.2. Preparation of silica supported ceric ammonium nitrate catalyst 77
5.3.3. Typical procedure for the synthesis of 3-aryl-3,4-dihydro-1,2,4- 78
benzothiadiazine-1,1-dioxides 78
5.3.4. Spectral Characterization data 78
5.4. Conclusion 83
5.5. References 84
Part II: Synthesis, biological activity and structural investigation of diversified piperidine-4-one 86
II.I. Introduction 86
II.II. Present work 87
II.III. References 88
Chapter 1. Synthesis of N-benzylated 3-alkyl-2,6-diarylpiperidin-4-ones: Stereochemical investigation by 1D/2D NMR and single-crystal XRD 89
1.1. Inroduction 89
1.2. Result and Discussion 90
1.2.1. Synthesis of compounds 90
1.2.2. 1H NMR spectral study of 1-benzyl-3-alkyl-2,6-diarylpiperidin-4-ones 22-25 100
1.2.3. Single-crystal XRD study of 1-benzyl-3-ethyl-2,6-diarylpiperidin-4-one 22 106
1.2.4. 13C NMR spectral study of 1-benzyl-3-ethyl-2,6-diarylpiperidin-4-one (22) 110
1.2.5. 1H and 13C NMR spectral study of 1-benzyl-3-methyl-2,6-diarylpiperidin-4-ones (14-21) 114
1.2.6. 1H and 13C NMR spectral study of 1-benzyl-3-isopropyl-2,6-diphenylpiperidin-4-one (26) 115
1.3. Experimental 117
1.3.1. Materials and methods 117
1.3.2. Recording of 1D NMR spectra 117
1.3.3. Recording of 2D NMR spectra 117
1.3.4. Recording of single-crystal XRD 118
1.3.5. Synthesis of 1-benzyl-3-alkyl-2,6-diarylpiperidin-4-ones (14-26) 120
1.4. Conclusion 121
1.5. References 122
Chapter 2. Synthesis and stereochemistry of highly crowded N-benzylpiperidones using 1D NMR and single-crystal XRD 124
2.1. Inroduction 124
2.2. Result and Discussion 125
2.2.1. Synthesis of compounds 125
2.2.2. Analysis of the IR spectrum of compounds 1-8 131
2.2.3. Proton and 13C NMR spectral analysis of compound (3) 133
2.2.2. Single-crystal XRD analysis of 1-benzyl-3,5-dimethyl-2,6-diphenylpiperidin-4-one (4) 137
2.2.3. The effect of N-benzylation on proton and carbon chemical shifts 145
2.3. Experimental 146
2.3.1. Materials and methods 146
2.3.2. Recording of one-dimensional NMR spectra 148
2.3.3. Recording of single-crystal XRD 148
2.3.4. Synthesis of 3,5-dialkyl-2,6-diarylpiperidin-4-ones (1-3) 149
2.3.5. Synthesis of 1-benzyl-3,5-dialkyl-2,6-diarylpiperidin-4-ones (4-8) 149
2.4. Conclusion 151
2.5. References 152
Chapter 3. Design, Synthesis and Cytotoxicity of Novel N-benzylpiperidin-4-one oximes on Human cervical cancer cells 154
3.1. Inroduction 154
3.2. Result and Discussion 155
3.2.1. Chemistry 155
3.2.2. Cytotoxicity 159
3.2.3. Altered morphology study 165
3.3. Experimental 166
3.3.1. NMR experiments 166
3.3.2. Single-crystal XRD 167
3.3.3. General procedure for the synthesis of 2,6-diarylpiperidin-4-ones (1a–1o) 167
3.3.4. General procedure for the synthesis of 1-benzyl-2,6-diarylpiperidin-4-ones (2a-2o) 168
3.3.5. General procedure for the synthesis of 1-benzyl-2,6-diarylpiperidin-4-one oximes (3a-3o) 168
3.3.6. Cytotoxicity assay (MTT assay) 168
3.3.7. Altered morphology study 169
3.3.8. Spectral Characterization data 170
3.4. Conclusion 175
3.5. References 176
Chapter 4 178
4.1 Summary………………………………………………………………………..178
4.2 List of publication from the present study ……………………………………..180
- Degree
- Doctor
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