Sebastian Wendeborn

Herbicidal 4-hydroxyphenylpyruvate dioxygenase inhibitors--a review of the triketone chemistry story from a Syngenta perspective.

A review, outlining the origins and subsequent development of the triketone class of herbicidal 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors.

A Convergent Approach toward the C1−C11 Subunit of Phoslactomycins and Formal Synthesis of Phoslactomycin B

The preparation of the C1-C11 subunit of phoslactomycins, and a formal synthesis of phoslactomycin B, were achieved by a convergent strategy involving the chelation-controlled addition of an alkynyl Grignard reagent to an alpha-alkoxy ketone. Catalytic enantioselective reductions of acetylenic ketones and a [2,3]-Wittig rearrangement were utilized as key steps to control the configuration of the C4, C5, and C9 stereocenters.

Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 2: Pyridazines

Special tetrasubstituted pyridazines are potent fungicides by promoting the tubulin polymerisation, hereby disrupting the microtubule dynamics in the fungus. They are monocyclic analogs of similar substituted triazolopyrimidines and pyridopyrazines with the same mode of action. The fungicidal activity of these pyridazines was evaluated against the plant pathogens Botrytis cinerea (grey mould), Mycosphaerella graminicola (wheat leaf blotch) and Alternaria solani (potato and tomato early blight). Structure-activity relationship studies revealed the importance of a methyl and a chlorine substituent next to both ring nitrogen atoms and two aryl or heteroaryl groups in the other two pyridazine positions.

Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 1: pyrido[2,3-b]pyrazines.

BACKGROUND The excellent fungicidal activity of [1,2,4]triazolo[1,5-a]pyrimidines suggested the search for further analogues with improved properties. RESULTS A series of novel trisubstituted pyrido[2,3-b]pyrazines has been designed and prepared as 6,6-biheterocyclic analogues of related 5,6-bicyclic [1,2,4]triazolo[1,5-a]pyrimidines. Their fungicidal activity was evaluated against the plant pathogens Puccinia recondita Rob. ex Desm. f. sp. tritici (Eriks.) CO Johnston (wheat brown rust), Mycosphaerella graminicola (Fuckel) Schroter (Septoria tritici Rob., leaf spot of wheat) and Magnaporthe grisea (Hebert) Barr (Pyricularia oryzae Cav., rice blast). Structure-activity relationship studies revealed the advantage of a fluoro substituent in position 6 and of a secondary amine in position 8. CONCLUSION 8-Amino-7-aryl-6-halogen-substituted pyrido[2,3-b]pyrazines have been prepared as 6,6-biheterocyclic analogues of similarly substituted triazolopyrimidine fungicides. A concise four-step synthesis route has been worked out to prepare these novel compounds from commercially available starting materials. [(R)-(1,2-Dimethylpropyl)]-[6-fluoro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazin-8-yl]amine showed excellent activity against three economically important phytopathogens.

Aryldiones incorporating a [1,4,5]oxadiazepane ring. Part 2: Chemistry and biology of the cereal herbicide pinoxaden†

BACKGROUND Pinoxaden is a new cereal herbicide that provides outstanding levels of post-emergence activity against a broad spectrum of grass weed species for worldwide selective use in both wheat and barley. RESULTS Factors influencing activity and tolerance to pinoxaden were in part linked to distinct structural parts of the active ingredient. Three complementary contributions that decisively impact upon the herbicidal potency against grasses were identified: a preferred 2,6-diethyl-4-methyl aromatic substitution pattern, a dione area suitable for proherbicide formation and beneficial adjuvant effects. The uptake and translocation pattern of pinoxaden when coapplied with its tailored adjuvant were analysed by autoradiography, indicating extensive and rapid penetration, followed by effective distribution throughout the plant. Crop injury reduction on incorporation of the [1,4,5]oxadiazepane ring into the aryldione template was reinforced with safener technology. Comparative studies on the behaviour of pinoxaden applied either alone or in combination with the safener cloquintocet-mexyl demonstrated that addition of the safener resulted in significant enhancement of metabolic degradation in wheat and barley, providing excellent crop tolerance and a substantial selectivity margin without adverse effects on weed control. CONCLUSION The biological potential of pinoxaden and its active principle pinoxaden dione in terms of grass weed control and tolerance in cereals was fully exploited by inclusion of the safener cloquintocet-mexyl in the formulation in combination with a specific and tailor-made tank-mix adjuvant based on methylated rape seed oil.

New and efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides

Abstract A short, efficient synthesis of 5′-amino-5′-( S )-methyl-2′,5′-dideoxynucleosides 1 has been developed through the diastereoselective addition of methylmagnesium bromide or methyllithium to an intermediate tert -butylsulfinimide.

Towards novel amide-modified oligonucleotides: asymmetric synthesis of 5'-(S)-methyl-3'-carboxymethylene-3'-deoxythymidine

Abstract The synthesis of novel 5′-( S )-methyl-3′-carboxymethylene-3′-deoxythymidine is reported. Key steps involve diastereoselective lactonization, enantioselective enzymatic ester hydrolysis and diastereoselective glycosidation of a key intermediate with thymine with 100% β-selectivity via Lewis acid mediated cleavage of a [3.2.1] oxabicyclic lactone.

1.8 Chirality in Agrochemicals

In the chapter agrochemical products, aspects of chirality of fungicides, insecticides, and herbicides reported in the last 30 years are reviewed. The chapter is structured by the respective biochemical modes of actions of the different substance classes discussed. Approaches to enantiomerically enriched chemicals are reported which include asymmetric catalysis, the use of building blocks from the chiral pool, as well as a number of different resolution methods. The authors provide detailed insights into the relevance of the chiral centers for the desired pesticidal activity and discuss, when possible, the molecular architecture in context with the underlying biochemical principles. Although the chapter focuses on the more recent agrochemicals, some of the old chemistries are reviewed when justified by relevant data revealed in the recent literature. Overall, the authors provide a concise overview of the chemistry, biology, and biochemistry of modern agrochemicals possessing one or several stereochemical centers, which should be of relevance to students and professionals interested in the chemical science of modern pesticides.