臺灣博碩士論文加值系統

第一部分，利用皮克特－施彭格勒反應合成四氫異喹啉後，與異氰酸硫酯、異氰酸硒酯進行[3+2]環化反應合成咪唑並[1,5-b]異喹啉，或與氯化乙醯氯及一級胺反應合成吡嗪並[1,2-b]異喹啉，並建立分子庫。

第二部分，以一鍋化兩步的方法合成含硫、氧、硒之有生物活性潛力的雜環小分子。

The first part deals with the diastereoselective synthesis of thio(seleno)-hydantoin-fused tetrahydroisoquinolines and diketopiperazine-fused tetrahydro-isoquinolines via the molecular hybridization synthetic strategy.

The second part describes the one-pot regioselective synthesis of chiral 2-iminothia(selena)zole derivatives and 2-thio(seleno)xoimidazolin-4-ones through multi-component reactions.

ACKNOWLEDGEMENT i
ABSTRACT ii
TABLE OF CONTENT v
LIST OF SCHEMES viii
LIST OF FIGURES ix
LIST OF TABLES x
LIST OF EQUATIONS x

CHAPTER. I
Diastereoselective Synthesis of Thio(seleno)hydantoin-fused tetrahydroisoquinolines and diketopiperazine-fused tetra-hydroisoquinolines

1.1 Introduction 1
1.1.1 Tetrahydroisoquinoline (TIQ) 1
1.1.2 Biological importance of hydantoin scaffold 2
1.1.3 2,5-Diketopiperazine scaffold 3
1.1.4 Molecular hybridization techniques 5
1.2 Motivation 6
1.3 Results and Discussion 9
1.3.1 Preparation of starting materials 9
1.3.2 Pictet-Spengler (P-S) reaction 12
1.3.2.1 Introduction 12
1.3.2.2 Synthesis of TIQ intermediates 14
1.3.2.3 Catalyst and solvent screening 15
1.3.2.4 Diastereoselectivity of P-S cyclization
17
1.3.2.5 Mechanism of this P-S cyclization 22
1.3.3 Hybridization of Bioactive Scaffolds 23
1.3.3.1 TIQ-Hydantoin Hybridization 23
1.3.3.2 TIQ-Diketopiperazine Hybridization 34
1.4 Conclusion 39
1.4 References 40
1.6 Experimental Section 44
1.6.1 General Methods 44
1.6.2 Experimental Procedure 45
1.7 Spectral data of compounds 49
1.7.2 Hydantoin-fused TIQs 3-2 53
1.7.3 Diketopiperazine-fused TIQs 4 71
1.7.4 ORTEP Data 84
1.7.4.1 trans-TIQs 2-trans 84
1.7.4.2 cis-TIQs 2-cis 93
1.7.4.3 Hydantoin-fused TIQs 3j-2 102
1.7.4.4 Diketopiperazine-fused TIQs 4d-cis 138

CHAPTER. II
One-pot regioselective synthesis of chiral 2-iminothia (selena)zole derivatives and 2-thio(seleno)-xoimidazolin-
4-ones

2.1 Introduction 151
2.1.1 Medicinal importance of Iminothiazoles 151
2.1.2 Biological importance of 2-thioxoimidazolin-4-
one motif 152
2.1.3 Organoselenium compounds 152
2.1.4 Multicomponent reactions (MCRs) 154
2.2 Motivation 155
2.3 Results and Discussion 157
2.3.1 Preparation of starting materials 157
2.3.1.1 Synthesis of amino propanoate 1a 157
2.3.1.2 Synthesis of isoselenocyanate 22b 157
2.3.2 Synthesis of 2-iminozoles and 2-imidazolin-4-
ones 159
2.3.3 Mechanism 161
2.3.4 Optimization 163
2.3.5 Substrate Scope 166
2.4 Conclusion 171
2.5 References 172
2.6 Experimental Section 175
2.6.1 General Methods 175
2.6.2 Experimental Procedure 176
2.7 Spectral data of compounds 180
2.7.1 Thio(seleno)urea intemediate 25a 180
2.7.2 2-iminothio(seleno)zole 27a 183
2.7.3 Thio(seleno)hydatoin intermediate 26a 200
2.7.4 2-imidazolin-4-ones 28a 204
2.7.5 ORTEP Data 225
2.7.5.1 Hydrated 2-imidazolin-4-ones 28f 225

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