1 Overview
1.1 Introduction
1.1.1 Mode of Action of Herbicide
1.1.2 Herbicide Resistance
1.1.3 New Opportunity for Novel Herbicides
1.1.4 Basic Methodology for Discovery of Hit/Lead Compounds
1.2 Pyruvate Dehydrogenase Complex （PDHc）
1.2.1 Function of PDHc
1.2.2 Distribution of PDHc
1.2.3 Plant PDHc E1.as Site of Action of Herbicide
1.3 Progress in the Research of PDHc Inhibitors
1.3.1 OP Compounds as Inhibitors of E coli PDHc
1.3.2 OP Compounds as Inhibitors of Plant PDHc
1.3.3 Enzyme-Selective Inhibition of OP Compounds
1.4 Design of Novel PDHc E1 Inhibitors as Herbicides
1.4.1 Selecting Plant PDHc E1.as Target of New Herbicide
1.4.2 PDHc E1 Inhibitor Acylphosphonate as Hit Compound
1.4.3 Finding Lead Structure IA
1.4.4 Optimization Strategy
1.5 Book Chapter Organization
References


2 Alkylphosphonates
2.1.（Alkyl or Substituted Phenyl）Methylphosphonates IA-IF
2.1.1 Introduction
2.1.2 Synthesis of O，O-Dialkyl
1-Hydroxyalkylphosphonates M2
2.1.3 Synthesis of Substituted Phenoxyacetic Acids M
and Substituted Phenoxyacetyl Chlorides M5
2.1.4 Synthesis of IA-IF
2.1.5 Spectroscopic Analysis of IA-IF
2.1.6 Crystal Structure Analysis of IC-7
2.1.7 Herbicidal Activity of IA-IF
2.1.8 Structure-Herbicidal Activity Relationships
2.1.9 Herbicidal Activity of IC-22.
2.1.10 Summary
2.2 Heterocyclylmethylphosphonates IG-IJ
2.2.1 Introduction
2.2.2 Synthesis of IG-IJ
2.2.3 Spectroscopic Analysis of IG-IJ
2.2.4 Crystal Structure Analysis of IH-18.and IG-21
2.2.5 Herbicidal Activity of IG-IJ
2.2.6 Structure-Herbicidal Activity Relationships
2.2.7 Herbicidal Activity of IG-21.
2.2.8 Summary
2.3.（1-Phenyl-1，2，4-Triazol-3-yloxyacetoxy）Alkylphosphonates IK
2.3.1 Introduction
2.3.2 Synthesis of IK
2.3.3 Spectroscopic Analysis of IK
2.3.4 Herbicidal Activity of IK
2.3.5 Summary
References


3 Salts of Alkylphosphonates
3.1 Alkali Metal Salts of O-Alkyl Alkylphosphonic Acids IIA-IIE
3.1.1 Introduction
3.1.2 Synthesis of IIA-IIE
3.1.3 Spectroscopic Analysis of IIA-IIE
3.1.4 Crystal Structure Analysis of IIB-20
3.1.5 Herbicidal Activity of IIA-IIE
3.1.6 Summary
3.2 Alkali Metal Salts of Alkylphosphonic Acids IIF，IIGandIIH
3.2.1 Introduction
3.2.2 Synthesis of IIF， IIG and IIH
3.2.3 Spectroscopic Analysis of IIF， IIG and IIH
3.2.4 Herbicidal Activity of IIF， IIG and IIH
3.2.5 Summary
3.3.t-Butylaminium Salts of Alkylphosphonates IIJ
3.3.1 Introduction
3.3.2 Synthesis of IIJ
3.3.3 Spectroscopic Analysis of IIJ
3.3.4 Crystal Structure Analysis of IIJ
3.3.5 Herbicidal Activity of IIJ
3.3.6 Summary
References


4 Alkylphosphinates
4.1 Alkylphosphinates IIIA-IIIG
4.1.1 Introduction
4.1.2 Synthesis of Dichloro（Methyl）Phosphine M10
4.1.3 Synthesis of O-Methyl （1-Hydroxyalkyl）-Methylphosphinates M12.
4.1.4 Synthesis of IIIA-IIIG
4.1.5 Spectroscopic Analysis of IIIA-IIIG
4.1.6 Crystal Structure Analysis of IIIE-
4.1.7 Herbicidal Activity of IIIA-IIIG
4.1.8 Summary
4.2 Sodium Salts of Alkylphosphinic Acids IIIH
4.2.1 Introduction
4.2.2 Synthesis of IIIH
4.2.3 Spectroscopic Analysis of IIIH
4.2.4 Herbicidal Activity of IIIH
4.2.5 Summary
4.3.[（5-Methylisoxazol-3-yloxyacetoxy）Alkyl]-Methylphosphinates IIIJ
4.3.1 Introduction
4.3.2 Synthesis of IIIJ
4.3.3 Spectroscopic Analysis of IIIJ
4.3.4 Herbicidal Activity of IIIJ
4.3.5 Summary
References


5 Cyclic Phosphonates and Caged Bicyclic Phosphates
5.1 Cyclic 1-Hydroxyalkylphosphonates IVA and IVB
5.1.1 Introduction
5.1.2 Synthesis of IVA and IVB
5.1.3 Spectroscopic Analysis of IVA and IVB
5.1.4 Crystal Structure Analysis of IVA-3
5.1.5 Herbicidal Activity of IVA and IVB
5.1.6 Summary
5.2 Cyclic Alkylphosphonates IVC-IVF
5.2.1 Introduction
5.2.2 Synthesis of IVC-IVF
5.2.3 Spectroscopic Analysis of IVC-IVF
5.2.4 Crystal Structure Analysis of IVC-
5.2.5 Herbicidal Activity of IVC-IVF
5.2.6 Summary
5.3 Caged Bicyclic Phosphates IVG and IVH
5.3.1 Introduction
5.3.2 Synthesis of IVG and IVH
5.3.3 Spectroscopic Analysis of IVG and IVH
5.3.4 Crystal Structure Analysis of IVG-
5.3.5 Herbicidal Activity of IVG and IVH
5.3.6 Summary
References


6 Optically Active Alkylphosphonates
6.1 Optically Active 1-Hydroxyalkylphosphonates IVB and M2
6.1.1 Introduction
6.1.2 Asymmetric Synthesis of 1-Hydroxyalkylphosphonates IVB and M2.via Hydrophosphonylation
6.1.3 Asymmetric Synthesis of 1-Hydroxyalkylphosphonates M2.via Hydroxylation
6.1.4 Summary
6.2 Optically Active （Substituted Phenyl）methylphosphonates IA，IEandIF
6.2.1 Introduction
6.2.2 Synthesis of Optically Active IA， IE and IF
6.2.3 Herbicidal Activity of Optically Active IA，IEandIF
6.2.4 Summary
6.3 Optically Active Substituted Ethylphosphonates IA and IC
6.3.1 Introduction
6.3.2 Synthesis of Optically Active IA and IC
6.3.3 Herbicidal Activity of Optically Active IA and IC
6.3.4 Aquatic Toxicity of Optically Active IA and IC
6.3.5 Summary
References


7 Biochemical Mechanism of Alkylphosphonates
7.1 Molecular Docking and 3D-QSAR Studies
7.1.1 Introduction
7.1.2 Binding Conformational Analysis
7.1.3 CoMFA and CoMSIA Analysis
7.1.4 Validation of the 3D-QSAR Models
7.1.5 Molecular Docking
7.1.6 Molecular Alignment and 3D-QSAR Modeling
7.1.7 CoMFA Analysis and CoMSIA Analysis Modeling
7.1.8 PLS Calculations and Validations
7.1.9 Summary
7.2 Enzyme Inhibition
7.2.1 Introduction
7.2.2 Inhibitory Potency Against Plant PDHc
7.2.3 Kinetic Experiment of PDHc
7.2.4 Selective Enzyme Inhibition
7.2.5 Structure-Activity Relationships
7.2.6 Assay of PDHc from Plant
7.2.7 Assay of PDHc from E coli and Pig Heart
7.2.8 Assay of Other Enzymes
7.2.9 Summary
References


8 Evaluation and Application of Clacyfos and HWS
8.1 Evaluation of Clacyfos
8.1.1 Introduction
8.1.2 Physiochemical Properties
8.1.3 Stability of Clacyfos
8.1.4 Herbicidal Activity in Greenhouse
8.1.5 Systemic Property of Clacyfos
8.1.6 Rainfast Characteristics of Clacyfos
8.1.7 Field Trials of Clacyfos
8.1.8 Toxicity Evaluation
8.1.9 Environmental Fate
8.1.10 Residues
8.1.11 Adsorption of Clacyfos on Soils
8.1.12 Ecological Effects
8.1.13 Summary
8.2 Evaluation of HWS
8.2.1 Introduction
8.2.2 Physiochemical Properties
8.2.3 Herbicidal Activity in Greenhouse
8.2.4 Systemic Property of HWS
8.2.5 Rainfast Characteristics of HWS
8.2.6 Field Trials of HWS
8.2.7 Toxicity Evaluation
8.2.8 Ecological Effects
8.2.9 Summary
References


9 General Methodology
9.1 General Synthetic Procedure
9.1.1 Chemicals， Reagents， and Solvents
9.1.2 O，O-Dialkyl Phosphonates M1.
9.1.3 O，O-Dialkyl 1-Hydroxyalkylphosphonates M2.
9.1.4 O，O-Dialkyl 1-（Chloroacetoxy）-Alkylphosphonates M3.
9.1.5 Substituted Phenoxyacetic Acids M4.
9.1.6 Substituted Phenoxyacetyl Chlorides M5.
9.1.7 O，O-Dialkyl 1-（Substituted Phenoxyacetoxy）-Alkylphosphonates IA-IJ
9.1.8 Phenylhydrazinecarboxamide M6.and Sodium
Triazol-3-olate M7.
9.1.9.（1-Phenyl-1，2，4-Triazol-3-yloxyacetoxy）-Alkylphosphonates IK
9.1.10 Alkali Metal Salts of O-Alkyl Alkylphosphonic Acids IIA-IIE
9.1.11 O，O-Bis（Trimethylsilyl） Alkylphosphonates M8.and Alkylphosphonic Acids M9.
9.1.12 Alkali Metal Salts of Alkylphosphonic Acids IIF-IIH
9.1.13.t-Butylaminium Salts of Alkylphosphonates IIJ
9.1.14 Dichloro（Methyl）Phosphine M10.
9.1.15 O-Methyl Methylphosphinate M11.
9.1.16 O-Methyl （1-Hydroxyalkyl）Methylphosphinates M12
9.1.17 Alkylphosphinates IIIA-IIIG
9.1.18 Sodium Salts of Alkylphosphinic Acids IIIH
9.1.19.3-Hydroxy-5-Methylisoxazole Derivatives M13-M16.
9.1.20 O-Methyl [1-（5-Methylisoxazol-3-yloxyacetoxy）-Alkyl]Methylphosphinates IIIJ
9.1.21.1-Phenyl-2，2-Dimethyl-1，3-Propanediol M17
9.1.22 Cyclic Phosphonates M18.
9.1.23 Cyclic 1-Hydroxyalkylphosphonates IVA and IVB
9.1.24 Substituted Phenoxypropionic Acids M19
9.1.25 Substituted Phenoxypropionyl Chlorides M20
9.1.26 Cyclic Alkylphosphonates IVC-IVF
9.1.27.4-（Hydroxymethyl）-2，6，7-Trioxa-1-Phosphabicyclo-[2.2.2]Octane-1-One/Thione M21/M22.
9.1.28 Caged Bicyclic Phosphates IVG and IVH
9.1.29 Optically Active Cyclic 1-Hydroxyalkylphosphonates IVB
9.1.30 O，O-Diethyl （Substituted Benzyl）Phosphonates M23
9.1.31 Optically Active 1-Hydroxyalkylphosphonates M2
9.1.32 Optically Active （Substituted Phenyl）-Methylphosphonates IA， IE， and IF
9.1.33.1-Keto Phosphonates M24.and Vinylphosphonates M25.
9.1.34 Optically Active 1-Substituted Ethylphosphonates IAandIC
9.2 General Information of Structural Characterization
9.3 Herbicidal Activity Assay
9.3.1 Test in Petri Dishes
9.3.2 Test in Greenhouse
References
Index