Synthesis of fenthion sulfoxide and fenoxon sulfoxide enantiomers: effect of sulfur chirality on acetylcholinesterase activity.

Earlier reports have demonstrated that recombinant flavin-containing monooxygenase 1 (FMO1) catalyzes the oxidation of the organophosphate pesticide fenthion to (+)-fenthion sulfoxide in a stereoselective fashion. In order to elucidate the absolute configuration of the sulfoxide metabolite produced, we established an efficient synthesis of both enantiomers of fenthion sulfoxide, which were transformed into chiral fenoxon sulfoxides using a two-step protocol. The use of chiral oxidants, namely, N-(phenylsulfonyl)(3,3-dichlorocamphoryl) oxaziridines, afforded enantioenriched fenthion sulfoxides with high ee (>82%) from the parent sulfide.

Inactivation of the cytotoxic activity of repin, a sesquiterpene lactone from Centaurea repens.

Prolonged ingestion of Yellow Starthistle (Centaurea solstitialis) and Russian Knapweed (Centaurea repens) by horses has been shown to result in a fatal neurodegenerative disorder called equine nigropallidal encephalomalacia (ENE). Bioassay-guided fractionation of extracts from Centaurea species using the PC12 cell line have led to the identification of one of several putative agents, which may contribute to ENE, namely, the sesquiterpene lactone (SQL) repin (1), previously linked to ENE due to its abundance in C. repens.

Synthesis and in vitro biological evaluation of fluoro-substituted-4-phenyl-1,2,3,6-tetrahydropyridines as monoamine oxidase B substrates.

The substrate properties of three beta-fluoro-4-phenyl-1,2,3,6-tetrahydropyridines related to the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine have been examined in an effort to evaluate the contribution of electronic parameters to the MAO-B catalyzed allylic-alpha-carbon oxidation of the tetrahydropyridinyl system. The design, synthesis, and biological evaluation of these analogues are presented and correlations to amine ionization potentials versus substrate activity are discussed.