Episodes from the Continuous Search for Solutions against Downy Mildew Diseases

Abstract

Discovery background, lead optimization pathways, synthesis and structure–activity relationships of three different research projects searching for new active ingredients against downy mildew diseases are reported. These case studies, on which the author worked in three different decades in the research departments of Syngenta Crop Protection AG and its legacy company Novartis Crop Protection AG deal with inhibitors of cellulose synthase, tubulin polymerization and oxysterol-binding protein. Rarely used reactions, which have been applied within these projects, such as Seebach's variation of the Passerini reaction, the Bogert quinazoline synthesis and the carbonyldiimidazole-mediated Lossen rearrangement give proof of the significance of synthetic organic chemistry for modern crop protection.

Practical and Regioselective Synthesis of C-4-Alkylated Pyridines

“…Moreover, a proof of concept is shown for how the fungicide (oomycetes) candidate 54 could conceivably be accessed in a far more practical way from pyridine. Prior studies employed chemistry that was cost-prohibitive for the agrochemical industry commencing from 51 and employing expensive boronate ester 52 , N-oxide chemistry, toxic TMSCN, and a Pd catalyst to access 1,3-disubstituted 53 , which required a subsequent hydrogenation to remove the 3,4-unsaturation . In contrast, the two-stage Minisci approach from 6a accesses a synthetically equivalent intermediate 50 directly without any of those drawbacks.…”

Reversal of Functional Groups as a Useful Scaffold Hopping Tool in Agrochemistry

“…Further successful examples of amide reversal have been reported in the classes of scytalone dehydratase, cellulose synthase, , oxysterol binding protein , and histone deacetylase , inhibiting fungicides, as well as for Complex I inhibiting and GABA-gated chloride channel modulating insecticides …”

“…Final optimization of the aliphatic amine chain length and the substitution pattern of the pyrazole ring delivered chloranthraniliprole (6), which shows excellent control of lepidopteran species such as Spodoptera f rugiperda (fall armyworm), Plutella xylostella (diamondback moth), and Heliothis virescens (tobacco budworm) (Scheme 2). 2,9−13 Further successful examples of amide reversal have been reported in the classes of scytalone dehydratase, 14 cellulose synthase, 15,16 oxysterol binding protein 17,18 and histone deacetylase 19,20 inhibiting fungicides, as well as for Complex I inhibiting 21 and GABA-gated chloride channel modulating insecticides.…”

Organic Isocyanates and Isothiocyanates: Versatile Intermediates in Agrochemistry

“…Its amidation with 3-chlorosalicylic acid under peptide coupling conditions affords the highly active fungicide 9 (Scheme 1). 16,17…”