Fluoromevalonate acts as an inhibitor of insect juvenile hormone biosynthesis

Abstract

The potential of analogues of insect juvenile hormones (JHs) for pest control has been demonstrated by the application of methoprene for the selective control of certain insects, including several mosquito species, the cigarette beetle and the hornfly¹. Compounds that impede JH production could offer a potentially more attractive method of control because accelerated metamorphosis would shorten the lifetime of the larvae, the stage that usually does maximum damage to the host plant. Of the few anti-juvenile hormone (AJH) agents described^2–5, only precocenes evoke all the required biological responses, but they affect a few insect taxa of minor economic importance. Their activity is thought to result from cytotoxicity^6,7 in the corpora allata. In view of similarities between the biosynthesis of the carbon skeletons of insect JHs^8,9 and farnesyl pyrophosphate (a precursor of steroids and other terpenoids¹⁰), compounds that inhibit the early steps in the biosynthesis of cholesterol might be expected to suppress JHs. Although this concept has already been explored without success^11,12, we now report the inhibition of juvenile hormone biosynthesis (AJH activity, see Table 1 legend) by a fluorinated mevalonate tetrahydro-4-fluoromethyl-4-hydroxy-2H-pyran-2-one, FMev, Fig. 1) which until now was known only to be hypocholesterolaemic^13–15.