Chemical studies of proteins that degrade pheromones : Cyclopropanated, fluorinated, and electrophilic analogs of unsaturated aldehyde pheromones.

Aldehyde components of lepidopterous pheromones are converted to carboxylic acids by aldehyde oxidizing enzymes (AOEs) that are present at high levels in antennal tissues of adult moths. The AOEs may include O2-requiring aldehyde oxidases as well as nucleotide-cofactor-requiring aldehyde dehydrogenases. Three classes of inhibitors were synthesized and examined in vitro for AOE inhibition usingHeliothis virescens antennae: (1) cyclopropanols, (2) α-fluorinated aldehydes, and (3) α,β-unsaturated carbonyls. First, cyclopropanated analogs of (Z)-11-hexadecenal (Z11-16∶A1), a common unsaturated aldehyde component of many species' pheromone blends, were synthesized as isosteric pheromone analogs and as potential inhibitors of the moth AOEs. NMR assignments are reported for thecis- andtrans-cyclopropanols. Cyclopropanols appear to act as oxidase-activated AOE inhibitors, perhaps via the unstable cyclopropanones. Second, α-fluoro and α,α-difluoro substituted analogs ofZ9-14∶A1 were synthesized and shown to be modest inhibitors of both the alcohol oxidase and AOE activities. Finally, the most potent inhibitors were α,β-unsaturated carbonyl mimics of theZ11-16∶A1. The α-methylene aldehyde was 1000-fold less effective than the vinyl ketoneZ1,11-16∶3-oxo. This inhibition appears irreversible and is postulated to involve electrophilic modification of an active site sulfur nucleophile.