Optically active disparlure analogs via resolution of a racemic precursor

The chief component of the gypsy moth (Lymantria dispar) semiochemical plume is (+)-(7R, 8 S)-cis-7,8-epoxy-2-methyl-octodecane, also called (+)-disparlure. Both enantiomers of disparlure and a variety of chiral analogs were required to probe the extremely sensitive and selective L. dispar pheromone olfactory system. Starting from propargyl alcohol, the racemic p-bromobenzoyl ester of cis-(2,3)-epoxytridecan-1-ol was synthesized and the enantiomers resolved on preparative liquid chromatographic column of microcrystalline cellulose triacetate I. From (+), (−) and (±)-cis-2,3-epoxytridecan-1-al were prepared (+), (−) and (±)-cis-(7,8)-epoxy-2-methyl-octadec-5-ene respectively in a Wittig reaction. The (+), (−) and (±)-(2,3)-epoxy-1-(3-methyl-butoxy) tridecanes were generated from the (−), (+) and (±)-epoxy alcohols via a Williamson ether synthesis. Racemic (2,3)-epoxy-1-(3-methyl-butylamino) tridecane was prepared from the reductive coupling of the epoxy aldehyde and 2-methylbutylamine. The epoxy amine quickly converted to anti-5-(1-hydroxy-undecyl)-3-(3-methyl-butyl)-oxazolidin-2-one in the presence of atmospheric CO₂. Racemic disparlure was synthesized by displacement of the cis-epoxy-p-toluenesulphonate of the epoxy alcohol with a dialkyllithium cuprate. In preliminary electroantennogram experiments with the analogs, the epoxy ether analogous to (+)-disparlure elicited the largest neural response. The optically-active epoxy alcohols, epoxy ethers, and epoxy alkenes, in addition to the racemic oxazolidinone, all exhibited low intrinsic electrophysiological activity. These compounds will be tested for their inhibition of the natural pheromone. Forthcoming binding assays will test the relative affinities of the two gypsy moth pheromone binding proteins for the chiral and racemic analogs.