面向药物合成的碱促进醇自身氢转移氧化胺化合成吲哚

摘要

在现在有机合成中，出于环境以及原子经济性方面的考虑，发展环境友好、高效的的新的合成方法学十分的重要。无需过渡金属催化的方法对于医药化学、生物研究领域十分重要，因为它们可以避免有害金属残留。
　　本论文主要论述了碱促进的、无需过渡金属催化的、基于空气氧化的吲哚合成方法，内容主要包括以下两方面:利用芳基取代的氨基醇来制备取代的吲哚和通过Wittig中间体来合成取代的酮。
　　1.第一部分的第一章节主要讲述了有关吲哚的背景介绍、它的重要性、应用价值以及生物活性，重点突出了由氨基醇合成吲哚的方法、非过渡金属催化的迫切性和重要性。
　　2.第二章节讲述了通过KOH促进的、无过渡金属添加的方法由取代氨基醇制备吲哚以及该方法在潜在抗胸腺癌细胞药物合成的应用。通过条件筛选发现用甲苯作溶剂、2.5equiv KOH以及120度反应条件下可以以优秀的产率得到吲哚，并且具有很强的底物适用范围。这个对于脂肪基的氨基醇也适用。这个方法可以有效的克级制备潜在抗胸腺癌细胞药物。
　　3.第三章讲述了叔丁醇钾促进的、无过渡金属添加的由二苯基溴甲烷经过Wittig中间体制备二苯甲酮的方法。通过条件筛选，我们发现DMF作溶剂、2.5equiv叔丁醇钾、80度的条件可以以优秀的转化率得到二苯甲酮。

目录

声明

摘要

ABSTRACT

TABLE OF CONTENTS

LIST OF SCHEMES

LIST OF TABLES

Chapter 1 Introduction

1．1 Advantages of transition metal free protocol

1．1．1 Transition metal free green chemistry approach

1．1．2 Advantages of Transition-Metal-Free synthesis

1．1．3 Need of TMF protocol

1．1．4．Limitation of transition metal catalysis

1．2 Indole an overview

1．2．1 Introduction to indole

1．2．2．Indoles in natural products

1．2．3 Biological and medicinal importance of indole

1．2．4 Indole ring containing important marketed drugs molecules

1．3 Review on indole synthesis from aromatic amino alcohol

1．3．1 Homogeneous Catalysis

1．3．2 Heterogeneous catalyzation of amino alcohols to indole

1．3．3 Production of indole in water

1．4 Review of amino alcohol to indole(a critical analysis)

1．4．1 Homogeneous catalysis

1．4．2．Heterogeneous catalysis

1．5 Transition metal-free synthesis of indole

1．5．1 Fischer indole synthesis

1．5．2 Metal free indole synthesis using DDQ as oxidant

1．5．3 Metal free Se-catalyzed indole synthesis

1．6 Motivation and Thesis outline

References

Chapter 2．Synthesis and Characterization of Indole

2．1 Introduction to TMF，base promoted，aerobic oxidative cyelization of indole

2．2 Results and discussions

2．2．1 Optimization of reaction condition

2．2．2 Scope of reaction

2．3 Experimental Section

2．3．1 Materials

2．3．2．Analytical Methods

2．3．3 Experimental Methods for amino alcohol preparation

2．4 Applications of the protocol

2．4．1 Gram scale Total synthesis of Potent anti-breast-cancer drug(2-31)

2．4．2 Experimental procedure for suzuki cross coupling reaction

2．5 Charaeterization

2．5．1 Characterization of amino alcohols

2．5．2 Characterization of 2-substituted aliphatic amino alcohols

2．5．3 Characterization of indole(NMR Spectra)

References

Chapter 3．Aerobic oxidative Synthesis ofBenzophenone via Wittig Reagent

3．1 Introduction to ketone synthesis via Wittig intermediate

3．1．1 Background

3．1．2 One-pot Synthesis of Benzophenone via Wittig Intermediate

3．2．1 Optimization of reaction condition

3．3 Control reactions for understanding the pathway mechanism and of ketone synthesis

3．3．1 Experimental verification for understanding the pathway of ketone synthesis

3．3．2 Control reactions for understanding the addition of Base after ylide formation

3．5 Conclusion

References

NMR Specta of Compounds

Acknowledgments

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