Environment-Friendly Antiviral Agents for Plants (eBook)

Title Page 2
Copyright Page 3
Foreword 4
Preface 6
Table of Contents 11
Introduction 17
Chapter 1 Studies on a-Aminophosphonates with Antiviral Activity 22
1.1 Organocatalytic Synthesis and Antiviral Activity of Asymmetric - a Aminophosphonates 22
1.1.1 Introduction 22
1.1.2 Materials and Methods 23
1.1.2.1 General 23
1.1.2.2 Synthesis and Characterization of Chiral Bronsted Catalyst 1.4 and Intermediates 24
1.1.2.3 General Procedure for Aldimines 1.2 25
1.1.2.4 General Procedure for Fluorinated Asymmetric a-aminophosphonates 1.5 26
1.1.2.5 Antiviral Biological Assay 26
1.1.3 Results and Discussion 27
1.1.4 Conclusions 33
1.2 Synthesis & Bioactivity of a-Aminophosphonates Containing Amide Moiety
1.2.1 Introduction 34
1.2.2 Materials and Methods 35
1.2.3 Results and Discussion 37
1.2.4 Conclusions 39
1.3 Green Synthesis & Bioactivity of a- Aminophosphonates Containing an Alkoxyethyl Moiety
1.3.1 Introduction 40
1.3.2 Materials and Methods 41
1.3.3 Results and Discussion 42
1.3.4 Conclusions 45
1.4 Green Synthesis & Bioactivity of Brominated a- Aminophosphonates
1.4.1 Introduction 46
1.4.2 Materials and Methods 47
1.4.3 Results and Discussion 48
1.4.4 Conclusions 51
1.5 Synthesis & Bioactivity of a-Aminophosphonates Containing Trifluorinated Methyl Moiety
1.5.1 Introduction 51
1.5.2 Materials and Methods 52
1.5.2.1 Instruments 52
1.5.2.2 General procedure for the preparation of products 1.25a-1.25i 53
1.5.3 Results and Discussion 54
1.5.3.1 Chemistry 54
1.5.3.2 Biological Activity 58
1.5.4 Conclusions 59
1.6 Synthesis & Bioactivity of Chiral a-Aminophosphonates Containing Fluorine Moiety
1.6.1 Introduction 59
1.6.2 Materials and Methods 60
1.6.3 Results and Discussion 62
1.6.4 Conclusions 68
1.7 Green Synthesis of a-Aminophosphonates Containing Bromine and Fluorine under Ultrasonic Irradiation 69
1.7.1 Introduction 69
1.7.2 Materials and Methods 70
1.7.2.1 Apparatus and analysis 70
1.7.3 Results and Discussion 70
1.7.4 Conclusions 72
1.8 Synthesis & Bioactivity of a-Aminophosphonates Containing Isoxazole Moiety
1.8.1 Introduction 73
1.8.2 Materials and Methods 74
1.8.3 Results and Discussion 75
1.8.3.1 Crystal structure of 1.33c 77
1.8.4 Conclusions 79
1.9 Synthesis & Bioactivity of a-Aminophosphonates Containing Benzothiazole Moiety
1.9.1 Introduction 79
1.9.2 Materials and Methods 80
1.9.3 Results and Discussion 81
1.9.4 Conclusions 86
1.10 Chiral Separation & Bioactivity of a-Aminophosphonates Containing Benzothiazole Moiety
1.10.1 Introduction 86
1.10.2 Materials and Methods 87
1.10.2.1 Chemicals 87
1.10.2.2 Equipments 87
1.10.2.3 Instrumentation and Chromatographic conditions 88
1.10.2.4 Antiviral Bioassay 88
1.10.3 Results and Discussion 89
1.10.3.1 Analytical HPLC 89
1.10.3.2 Semi-preparative HPLC 95
1.10.3.3 Antiviral activity 97
1.10.4 Conclusions 99
1.11 Crystal Structure of O,O-Dipropyl-a-aminophosphonate Containing Benzothiazole Moiety 99
1.11.1 Introduction 99
1.11.2 Materials and Methods 99
1.11.3 Results and Discussion 100
References 101
Chapter 2 Synthesis, Characterization and Antiviral Activity of Cyanoacrylates and Derivatives 109
2.1 Synthesis and Antivival Activity of Cyanoacrylates Containing Phosphonyl Moiety 109
2.1.1 Introduction 109
2.1.2 Materials and Methods 110
2.1.3 Results and Discussion 111
2.1.4 Conclusions 116
2.2 Synthesis and Bioactivity of Cyanoacrylate Derivatives Containing Pyridine Moiety 116
2.2.1 Introduction 116
2.2.2 Materials and Methods 117
2.2.3 Results and Discussion 118
2.2.4 Conclusions 121
2.3 Preparation of Chiral Cyanoarylate Derivatives under Microwave Irradiation 121
2.3.1 Introduction 121
2.3.2 Materials and Methods 122
2.3.3 Results and Discussion 123
2.3.4 Conclusions 126
2.4 Preparation of Chiral Cyanoacylate Derivatives from Phenylethanamine 126
2.4.1 Introduction 126
2.4.2 Materials and Methods 128
2.4.2.1 Synthetic Procedures 128
2.4.2.2 General procedure for the preparation of intermediates 2.11a-2.11d 128
2.4.2.3 General procedure for the preparation of title compounds 2.12 128
2.4.2.4 Crystal structure determination 129
2.4.2.5 Antiviral Biological Assay 129
2.4.2.6 Herbicidal activity bioassay 129
2.4.2.7 MTT Assay against Cell Viability and Proliferation 129
2.4.3 Results and Discussion 129
2.4.3.1 Synthesis 129
2.4.3.2 Antiviral Activity 131
2.4.3.3 Herbicidal activity 132
2.4.3.4 Antiproliferation activity 132
2.4.3.5 Crystal Structure Analysis 133
2.4.4 Conclusions 134
2.5 Preparation and Antiviral Activity of Chiral Cyanoacylate Derivatives from Aryl (Heterocyclic) Amine 134
2.5.1 Introduction 134
2.5.2 Materials and Methods 135
2.5.2.1 General procedure for the preparation of intermediates 2.14a-2.14d 136
2.5.2.2 General procedure for the preparation of title chiral compounds 2.15 136
2.5.2.3 Crystal structure determination 136
2.5.2.4 Protection and inactivation and cure effect of compound against TMV in vivo 136
2.5.2.5 Determination of PAL and POD and SOD activity 136
2.5.2.6 RT-PCR assay 136
2.5.2.7 Semi-quantity PCR for expression of gene 137
2.5.2.8 The relative quantification real-time PCR for expression of the target gene 137
2.5.2.9 Statistical analysis 137
2.5.3 Chemistry 138
2.5.3.1 Synthesis of novel chiral cyanoacrylate derivatives. 138
2.5.3.2 Crystal structure analysis. 139
2.5.4 Antiviral Activity 140
2.5.4.1 Preliminary antiviral activity assay 140
2.5.4.2 Effect of (R)-2.15p treatment on PAL, POD and SOD activity in tobacco. 140
2.5.4.3 Gene expression analysis of PR-1a and PR-5 in (R)-2.15-treatedtobacco leaf 142
2.5.5 Discussion 143
2.5.6 Conclusions 144
2.6 Preparation and Antiviral Activity of Chiral Cyanoacylate Derivatives Containing -Aminophosphonate Moiety 144
2.6.1 Introduction 144
2.6.2 Materials and Methods 145
2.6.3 Results and Discussion 146
2.6.4 Conclusions 150
2.7 Crystal Structure elucidation of Cyanoacrylates 151
2.7.1 Crystal Structure of (E)-Ethyl-3-[(S)-1-phenylethylamino]- 3-[4-(trifluoromethyl)- phenylamino]-2-cyanoacrylate 151
2.7.2 Characterization of Two Chiral Isomers of (E)-Ethyl-3- [(R) or (S)-1-phenylethyl amino]-3-[4-nitrophenylamino]-2- cyanoacrylate 157
References 161
Chapter 3 Synthesis and Antiviral Activity of Chiral Thiourea Derivatives 166
3.1 Chiral Thiourea Deravatives from Primary Amine and Isocyanate 166
3.1.1 Introduction 166
3.1.2 Materials and Methods 167
3.1.3 Results and Discussion 168
3.1.4 Conclusions 173
3.2 Chiral Thiourea Derivatives Containing a-Aminophosphonate Moiety 173
3.2.1 Introduction 173
3.2.2 Materials and Methods 175
3.2.3 Results and Discussion 176
3.2.4 Conclusions 179
References 179
Chapter 4 The Heterocyclic Antiviral Agents 182
4.1 Pyrazole Derivatives Containing Oxime Ester Moiety 182
4.1.1 Introduction 182
4.1.2 Materials and Methods 183
4.1.2.1 Analysis and Instruments 183
4.1.2.2 Preparation of pyrazolaldoxime ester derivatives (4.4a-4.4n) 183
4.1.2.3 Crystal structure determination 184
4.1.2.4 Protection and inactivation and cure effect of compound against TMV in vivo 184
4.1.2.5 Determination of PAL and POD and SOD activity 184
4.1.2.6 RT-PCR assay 184
4.1.2.7 The relative quantification real-time PCR for expression of the targetgene 185
4.1.2.8 The primary spectroscopic study of compound 4.4l for TMV CP 185
4.1.2.9 The determination of quenching constants 186
4.1.2.10 The primary spectroscopic study of compound 4.4l for TMV RNA 186
4.1.2.11 Statistical analysis 186
4.1.3 Chemistry 186
4.1.3.1 Synthesis of novel pyrazole derivatives 186
4.1.3.2 Crystal structure analysis 187
4.1.4 Antiviral Activity 188
4.1.4.1 Preliminary antiviral activity assay 188
4.1.4.2 Effect of 4.4l treatment on PAL, POD and SOD activity in tobacco 189
4.1.4.3 Gene expression analysis of PR-1a and PR-5 in 4.4l-treated tobacco leaf 190
4.1.4.4 The primary spectroscopic study of 4.4l for TMV CP 191
4.1.5 Discussion 195
4.1.6 Conclusions 196
4.2 Pyrazole Derivatives Containing Oxime Ether Moiety 197
4.2.1 Introduction 197
4.2.2 Materials and Methods 199
4.2.3 Results and Discussion 200
4.2.4 Conclusions 204
4.3 Quinazolinone Derivatives 205
4.3.1 Introduction 205
4.3.2 Materials and Methods 206
4.3.3 Results and Discussion 208
4.3.4 Conclusions 215
References 215
Chapter 5 Innovation and Application of Environment-Friendly Antiviral Agents for Plants 220
5.1 Innovation of New Antiviral Agent Dufulin[N-[2-(4-methyl-benzothiazol)]- 2-ylamino-2-fluophenyl-O,O-diethyl phosphonate] 220
5.1.1 Product Chemistry 221
5.1.2 Formulation of Dufulin 221
5.1.2.1 Formalation of 30% Dufulin suspension concentrate(SC) 222
5.1.2.2 Formalation of 30% Dufulin wettable powder(WP) 226
5.1.2.3 Formulations of 10% Dufulin Emulsion Concentrate(EC) 228
5.1.3 Optimization of Synthetic Conditions in Lab Scale and Pilot Scale 231
5.1.3.1 Introduction 231
5.1.3.2 Materials and Methods 231
5.1.3.3 Results and Discussion 232
5.1.3.4 Conclusions 235
5.1.4 Toxicology Test 237
5.1.4.1 Introduction 237
5.1.4.2 Methods 238
5.1.4.3 Results and discussion 238
5.1.4.4 Conclusions 239
5.1.5 Field Trials 240
5.1.5.1 Introduction 240
5.1.5.2 Materials and methods 241
5.1.5.3 Results and Discussion 242
5.1.5.4 Conclusion 244
5.1.6 Pesticide Residue 244
5.1.6.1 Introduction 244
5.1.6.2 Materials and Methods 245
5.1.6.3 Results and Discussion 246
5.1.6.4 Conclusions 251
5.1.7 Environmental toxicology 251
5.1.7.1 Introduction 251
5.1.7.2 Materials and Methods 251
5.1.7.3 Results 252
5.1.7.4 Conclusion 253
5.1.8 Mode of Action 253
5.1.8.1 Introduction 253
5.1.8.2 Materials and Methods 254
5.1.8.3 Results and Discussion 259
5.1.8.4 Conclusions 270
References 270
5.1.9 Photolysis and Hydrolysis 271
5.1.9.1 Introduction 271
5.1.9.2 Materials and Methods 272
5.1.9.3 Results 275
5.1.9.4 Conclusions 284
5.1.10 Systemic Behaviors 286
5.1.10.1 Introduction 286
5.1.10.2 Materials and methods 286
5.1.10.3 Results and disccussion 289
5.1.10.4 Conclusions 292
References 292
5.2 GU188, 2-Cyanoacrylate Derivative, Candidate Antiviral Agent 293
5.2.1 Synthesis 293
5.2.1.1 Introduction 293
5.2.1.2 Materials and methods 293
5.2.1.3 Results and discussion 294
5.2.1.4 Conclusions 297
5.2.2 Analytical Method 297
5.2.2.1 Introduction 297
5.2.2.2 Materials and methods 298
5.2.2.3 Results and discussion 299
5.2.2.4 Conclusions 299
5.2.3 Bioassays and Field Trials 300
5.2.3.1 Introduction 300
5.2.3.2 Materials and methods 300
5.2.3.3 Results and Discussion 300
5.2.3.4 Conclusions 301
5.2.4 Toxicological Test 302
5.2.4.1 Introduction 302
5.2.4.2 Methods 302
5.2.4.3 Results and discussion 302
5.2.4.4 Conclusions 303
5.2.5 Action Mechanism 303
5.2.5.1 Introduction 303
5.2.5.2 Materials and Methods 304
5.2.5.3 Results and Discussion 304
5.2.5.4 Conclusions 308
5.3 Studies on the Development of Novel Amino-oligosaccharide 308
5.3.1 Introduction 308
5.3.2 Anti-TMV and Mechanism of Action 309
5.3.2.1 Anti-TMV bioassay 309
5.3.2.2 Mechanistic study 309
5.3.2.3 Effects of 0.5% amino-oligosaccharin aqua on tobacco defense enzyme 310
5.3.3 Industrialization 311
Index 314