William Eldo Barnette

The discovery of indoxacarb: oxadiazines as a new class of pyrazoline-type insecticides†

The evolution of the insecticidal pyrazoline moiety that was originally discovered in 1972 has led to the discovery of a new crop insecticide, indoxacarb, which is the first commercialized pyrazoline-type sodium-channel blocker. Both monocyclic and fused-tricyclic pyrazolines and pyridazines, as well as structurally related semicarbazones were examined prior to the discovery of analogous tricyclic oxadiazines which had similarly high activity as well as favorable environmental dissipation rates and low toxicity to non-target organisms. The eventual leading candidate, DPX-JW062, was originally obtained as a racemic molecule, but a chiral synthesis was developed which produces material that is 50% ee in the insecticidal (+)-S-enantiomer (DPX-MP062, indoxacarb).

The synthesis and biology of fluorinated prostacyclins

Fluorination has been used extensively in the steroid field to alter and/or enhance activity and to increase chemical or biological stability taking advantage of the similarity in size between hydrogen and fluorine and its strong electronegativity. Thus, it is not surprising to find that the same principle has been applied to prostaglandins, more specifically prostacyclin. The specific activity and high instability of Prostacyclin make it an ideal candidate for similar fluorination techniques. The design and preparation of fluorinated analogs with the aim of improving the chemical and metabolic stability of this important molecule will be discussed.