Safe and Sustainable Crop Protection

Safe and Sustainable Crop Protection
ACS Symposium Series1334
	Safe and Sustainable Crop Protection
		Library of Congress Cataloging-in-Publication Data
Foreword
Preface
The Microbiome of Fruit Flies as Novel Targets for Pest Management
Modular Approach to Macrocyclic Picolinamides
Workflows for the Structure Elucidation of Impurities in Synthetic Agrochemicals Using Mass Spectrometry
Separation of Chiral Molecules in Support of Process Chemistry and Formulations Research
Optimization of Critical Parameters in Chiral Analysis of Prothioconazole by Supercritical-Fluid Chromatography–Mass Spectrometry
Characterization of Nonextractable Residues in Soil via Kinetics Modeling
Creating Environmentally Resilient Agriculture Landscapes Using Precision Agriculture Technology: An Economic Perspective
Contract Research, Good Laboratory Practices, and Other Challenges for the Agrochemical Professional
Editors’ Biographies
	Indexes
Indexes
Author Index
Subject Index
Preface
	1
The Microbiome of Fruit Flies as Novel Targets for Pest Management
	Invasive Fruit Flies: Small Insects of Big Economic Importance
	Current Status and Challenges of Fruit Fly Management
	The Fruit Flies’ Microbiome: Who Are the Players?
	Microbial Influence on Fruit Flies: Nutrition, Behavior, and Insecticide Resistance
	Leveraging Microbiomes to Develop Novel Management Strategies for Fruit Flies: Lessons from Different Insects
		Figure 1. Leveraging the microbiome of fruit flies to develop pest management strategies (using D. suzukii as an example).
	Suppression of Insect Performance by Modifying the Insect Microbiome
	Disruption of Microbiomes
	Incompatible Insect Technique
	Paratransgenesis
	Microbial-Based Attractants and Repellents
	Attractants
	Repellents
	Optimization of SITs Using Probiotics
	Concluding Remarks
	Acknowledgments
	References
		2
Modular Approach to Macrocyclic Picolinamides
	Figure 1. Structure of UK-2A.
	Figure 2. Structure–activity relationship investigations on UK-2A.
	Improving Molecule Stability
		Figure 3. Use of a hydrolyzable protecting group to increase the leaf surface stability of UK-2A.
		Figure 4. Macrocycle CAS-381 contains fewer esters and displays improved stability.
		Figure 5. Acetoxymethyl ether derivatives of UK-2A and CAS-381.
	Maximizing Synthetic Accessibility
		Figure 6. Seven additional scaffolds of CAS-385 with atom variations at the X, Y, and Z positions.
	Retrosynthesis Strategy
		Figure 7. Retrosynthetic strategy for the modular construction of X-YZ macrocycles.
	Synthesis of the Stereotriads
		Figure 8. Early- and late-stage incorporation of YZ substituents.
		Figure 9. Interconversion of olefinic and alcohol stereotriads.
	Stitching the Fragments Together
		Figure 10. Addition of an alcohol stereotriad into a Boc-aziridine carboxylate under Lewis acidic conditions.
		Figure 11. Formation of the X = CH2 bond.
	Macrocyclization
		Figure 12. Macrocyclization methods to create X-YZ macrocycles.
	Modular Construction
		Figure 13. Matching the synthetic inputs to create the desired X-YZ macrocycle.
	Biology Comparisons
		Figure 14. Scaffold markush for macrocycle derivatives with variations at the X,Y, and Z positions.
	Summary
	Acknowledgments
	References
		3
Workflows for the Structure Elucidation of Impurities in Synthetic Agrochemicals Using Mass Spectrometry
	Background
		Figure 1. The role of mass spectrometry in the pipeline.
	Mass Spectrometry Instruments
	HRMS Analyzers
	TOF and Quadrupole TOF
	Orbitrap
	Ionization Sources
	Other MS Technologies Applicable for Small-Molecule Structure Elucidation
		Figure 2. A typical workflow for impurity identification in synthetic AI samples.
	Typical Workflow for Impurity Identification
	Derivatization
		Figure 3. Derivatization of alcohols with 2-SBA for improved sensitivity in negative ion ESI/MS.
	Case Studies
	GC/MS Study of Impurities in a Commercial Chlorpyrifos Sample
		Figure 4. The total ion chromatograms of (a) Chlorpyrifos and (b) Chlorpyrifos derivatized with BSTFA.
		Figure 5. The EI and PCI-methane mass spectra of the impurity observed in chlorpyrifos derivatized with BSTFA.
		Scheme 1. Chlorpyrifos
	LC/MS Study of Impurities in a Commercial Haloxyfop-P Methyl Ester
		Scheme 2. Haloxyfop-P Methyl Ester
		Figure 6. The UV chromatogram of Haloxyfop-P methyl ester.
		Figure 7. The positive ion ESI mass spectrum of Haloxyfop-P methyl ester showing [M + H]+, [M + Na]+, and [M + K]+.
		Scheme 3. Major Fragment Ions Generated from Protonated Haloxyfop-P Methyl Ester
		Figure 8. The positive ion ESI MS/MS spectrum of [M + H]+ ions of Haloxyfop-P methyl ester.
		Figure 9. The negative ion ESI mass spectrum of Haloxyfop-P methyl ester showing [M − H]-, [M + O − H]+, and [M + O2 − H]+.
		Figure 10. The positive ion ESI mass spectrum of Imp 1 showing both [M + H]+ and [M + Na]+.
		Figure 11. The positive ion ESI MS/MS spectrum of [M + H]+ ions of Imp 1.
	Future Improvements
	Conclusion
	Acknowledgments
	References
		4
Separation of Chiral Molecules in Support of Process Chemistry and Formulations Research
	Introduction
	Workflow for Development of Chiral Separation Methods
	Step-by-Step Progression of Chiral Separation Method Development
		Figure 1. Progression of chiral separation method development. (1) Receive racemic and enantioenriched sample. (2) Identify mobile phase composition. (3) Perform chiral stationary phase screening. (4) Optimize separation on best stationary phase. (5) Run both samples using optimized separation conditions and optimized sample prep. (6) Document method.
	Key Learnings
		Figure 2. Mixture of chiral diastereomers (four isomers) and chiral byproducts (two enantiomers).
	Case Studies
	Example 1: Interesting Findings—When Your Stationary Phase Behaves Unexpectedly
		Figure 3. Mixture of four isomers to be separated, containing two pairs of enantiomers.
		Figure 4. Progression of separation during method development using an OJ chiral stationary phase. (1) 15% IPA/hex at 40 °C. (2) 3% IPA/hex at 20 °C (first injection). (3) 1% IPA/hex at 20 °C. (4) 3% IPA/hex at 20 °C (second injection).
		Figure 5. Chromatograms of epoxide isomers at 20 °C after (1) equilibration at ≥15% IPA/hex for 1h followed by a blank injection at 3% IPA/hex and (2) equilibration at <3% IPA/hex for 1h followed by a blank injection at 3% IPA/hex.
	Example 2: Creative Analytical-Scale Isolation
		Figure 6. Racemic molecule that needs to be separated into its enantiomers.
		Figure 7. Chiral separation of enantiomers that require isolation.
		Figure 8. Optimization of chiral separation conditions. (1) 2 mL/min, 5 μL injection of 1 mg/mL solution (0.005 mg), 214 nm. (2) 2 mL/min, 100 μL injection of 1 mg/mL solution (0.1 mg), 214 nm. (3) 2 mL/min, 100 μL injection of 10 mg/mL (1 mg), 214 nm. (4) 2 mL/min, 100 μL injection of 10 mg/mL (1 mg), 254 nm.
		Figure 9. Typical instrument configuration of Dionex Ultimate 3000 instrument.
		Figure 10. Modified instrumentation configuration to allow analytical-scale isolation.
		Figure 11. Example of how fractions were collected.
		Figure 12. Minor peak shifting observed during isolation run.
	Example 3: Application to Formulations
		Figure 13. Reanalysis of pooled fractions of both peaks showing each enantiomer was isolated in high enantiopurity.
		Figure 14. Structural motif of a racemic molecule that requires a chiral separation method.
		Figure 15. Chiral separation developed for racemic material was used to analyze enantioenriched technical, which was then used to generate a formulation for field trials.
		Figure 16. Interference screen with formulation components.
		Figure 17. Analysis of enantioenriched technical and formulation after 2 weeks at room temperature.
		Figure 18. Structural motif of alkylamide solvent.
		Figure 19. Hypothesized racemization pathway of enantioenriched material.
		Figure 20. Loss of enantiopurity observed upon addition of alkylamide solvent and dimethylamine to the formulation.
		Figure 21. Racemization is inhibited upon addition of acid to the formulation.
	Summary
	Acknowledgments
	References
		5
Optimization of Critical Parameters in Chiral Analysis of Prothioconazole by Supercritical-Fluid Chromatography–Mass Spectrometry
	Introduction
		Figure 1. Time difference of RP separation vs SFC separation of two chiral molecules.
	Experimental Section
	Sample Preparation
	SFC Instrumentation
	RPLC Instrumentation
		Figure 2. RPLC conditions and chromatograms.
	MS Instrumentation
	Results and Discussion
		Figure 3. Conditions and representative chromatograms of proton donor evaluation.
		Figure 4. Calibration curves of prothioconazole from 50 to 6500 ppb with water added through the modifier and makeup flow and without water.
		Figure 5. RPLC and SFC ionization comparisons of prothioconazole.
		Figure 6. RPLC and SFC ionization comparisons of prothioconazole-desthio.
		Figure 7. Comparison of prothioconazole ionization efficiency using optimal mode and polarity in RPLC and SFC.
		Figure 8. Comparison of prothioconazole-desthio ionization efficiency using optimal mode and polarity in RPLC and SFC.
		Figure 9. RPLC plot of S/N at different concentrations.
		Figure 10. SFC plot of S/N at different concentrations.
	Conclusion
	References
		6
Characterization of Nonextractable Residues in Soil via Kinetics Modeling
	Introduction
	Methodology
		Figure 1. Kinetics model to demonstrate the nature of nonextractable residue.
	Results and Discussion
		Figure 2. Conversion of methomyl metabolites to NER in soil.
		Figure 3. Kinetics model for oxime degradation.
		Figure 4. Conversion of oxime to NER in soil.
		Figure 5. Oxamyl degradation pathway.
		Figure 6. Oxamyl degradation and optimized data fit in soil.
		Figure 7. Degradation pathway of cymoxanil in soil.
		Figure 8. Optimized kinetics for conversion of cymoxanil to metabolites, NER, and CO2.
		Figure 9. Soil degradation pathway for cyhalofop butyl.
		Figure 10. Optimized kinetics for degradation of cyhalofop butyl.
		Figure 11. Degradation pathway for famoxadone in soil.
		Figure 12. Optimized kinetics degradation of famoxadone and its metabolite H3310 in soil.
	References
		7
Creating Environmentally Resilient Agriculture Landscapes Using Precision Agriculture Technology: An Economic Perspective
	Introduction
	Hindrances to Conservation Adoption
	Incentive-Based Conservation
	Mechanism for Conservation Delivery
	Precision Agriculture Technology
		Figure 1. Yield map (bushels per acre) for a production soybean field in Lowndes County, Mississippi.
	Precision Agriculture Application for Pesticide Mitigation
		Figure 2. Profit surface (dollar per acre) for a production soybean field in Lowndes County, Mississippi. Net Rev: net revenue.
		Figure 3. Total eligible area for CP-33, Filter Strips, on a grain farm in Tallahatchie, Mississippi. Reproduced with permission from reference 30. Copyright 2016 American Society of Agronomy, Crop Science Society of America, Soil Sciences Society of America.
		Figure 4. Total eligible area for CP-21, Habitat Buffers for Upland Birds, on a grain farm in Tallahatchie, Mississippi. Reproduced with permission from reference 30. Copyright 2016 American Society of Agronomy, Crop Science Society of America, Soil Sciences Society of America.
		Figure 5. Profit surface (dollar per acre) for a production soybean field with 30-foot CP-33, Habitat Buffers for Upland Birds, scenario in Lowndes County, Mississippi. Net Rev: net revenue.
		Figure 6. Profit surface (dollar per acre) for a production soybean field with 120-foot CP-33, Habitat Buffers for Upland Birds, scenario in Lowndes County, Mississippi. Net Rev: net revenue.
		Figure 7. Bar graph illustrating the economic outcomes of two conservation profitability scenarios on a soybean field in Lowndes County, Mississippi.
	Discussion
	References
		8
Contract Research, Good Laboratory Practices, and Other Challenges for the Agrochemical Professional
	The Evolution, History, and Market Demand for Contract Research Organizations
	Trends in the Agrochemical Industry
	The Regulatory Reality
	Surging toward Merging
	Challenges in the CRO Industry
	The Challenge of GLP
	Managing Data
	Compliance Starts with Training
	The Role of the SD
	The Challenge of an Aging Workforce
	The Challenge of Continuous Regulatory Change
	The Challenge of Flexibility
	The Challenge of Diversification
	The Challenge of New Technology
	The Holy Grail (Communication)
		Figure 1. The impact of communication initiatives at Eurofins on quality metrics. Major events in the second quarter of 2016 included establishing weekly Ops/QC/RW/QA meetings, new e-fate testing, and the established and management of a deviations tracking database (the second quarter of 2016) 6.
	Conclusions
	References
Editors’ Biographies
	Kari Lynn
	Mingming Ma
	Qiang Yang
	Qi Yao
Indexes
Author Index
Subject Index
	A
	C
	I
	M
	N
	P