Spiro N‐methoxy piperidine ring containing aryldiones for the control of sucking insects and mites: discovery of spiropidion

Abstract

BACKGROUND Crop protection solutions for the control of key economic sucking pests derive essentially from neuronal and muscular acting chemistries, wherein neonicotinoid uses largely dominated for the last two decades. Anticipating likely resistance development of some of those arthropod species to this particular class, we intensified research activities on a non‐neuronal site of action targeting insect growth and development some 10 years ago. RESULTS Our innovation path featured reactivation of a scarcely used and simple building block from the 1960s, namely N‐methoxy‐4‐piperidone 3. Its judicious incorporation into the 2‐aryl‐1,3‐dione scaffold of IRAC group 23 inhibitors of fatty acid biosynthesis resulted in novel tetramic acid derivatives acting on acetyl‐coenzyme A carboxylase (ACCase). The optimization campaign focused on modulation of the aryl substitution pattern and understanding substituent options at the lactam nitrogen position of those spiroheterocyclic pyrrolidine‐dione derivatives towards an effective control of sucking insects and mites. This work gratifyingly culminated in the discovery of spiro N‐methoxy piperidine containing proinsecticide spiropidion 1. Following in planta release, its insecticidally active dione metabolite 2 is translaminar and two‐way systemic (both xylem and phloem mobile) for a full plant protection against arthropod pests. CONCLUSION Owing to such unique plant systemic properties, growing shoots and roots actually not directly exposed to spiropidion‐based chemistry after foliar application nevertheless benefit from its long‐lasting efficacy. Spiropidion is for use in field crops, speciality crops and vegetables controlling a broad range of sucking pests. In light of other performance and safety profiles of spiropidion, an IPM fit may be expected. © 2020 Society of Chemical Industry

Status and outlook for acaricide and insecticide discovery

“…Spiropidion (ISO provisionally approved) is in development as a fourth KTE. 57 Compared with spirotetramat (R = CO-O-CH 2 -Me; Fig. 11), the new N-methyl tetramic acid derivative spiropidion contains a spiro N-methoxy piperidine moiety instead of the spiro methoxy cyclohexane moiety in spirotetramat (replacement of CH by N in the spirocyclic 6-ring).…”

“…Spiropidion (ISO provisionally approved) is in development as a fourth KTE 57 . Compared with spirotetramat (R = CO‐O‐CH 2 ‐Me; Fig.…”

“…12a). A result is the protection of young, untreated leaves and roots in whole cabbage plants 57 . Similar to spirotetramat‐enol (p K a = 5.2), spiropidion‐enol has suitable physico‐chemical properties such as being a weak acid with a p K a value of 5.53, which results in phloem mobility (Fig.…”

Pest management diversity from the 14th International Union of Pure and Applied Chemists (IUPAC) International Congress of Crop Protection Chemistry

“…Several research papers dealt with insecticides 14‐17 . Tick kinins for finding new targets for management of arthropod pests is studied, 14 and novel insect kinin analogues are synthesized and evaluated as insecticides in another paper 15 .…”

“…Tick kinins for finding new targets for management of arthropod pests is studied, 14 and novel insect kinin analogues are synthesized and evaluated as insecticides in another paper 15 . The synthesis and activity of a new acetyl‐coenzyme A carboxylase‐inhibiting proinsecticide, spiropidion, is provided by Muehlebach et al 16 . Insect capability neuropeptide analogues are examined as potential insecticides by Gui et al 17 .…”