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In order to provide additional insight into the mode of action of the trichothecene mycotoxins, one of the first semi-synthetic trichothecene epi-epoxides (8) has been prepared; in dramatic contrast to its natural isomer (9), this compound proved to be devoid of significant biological activity.

Efficient and general procedures have been developed for the solution-phase preparation of substituted morpholine derivatives, and a library has been produced around generic structure 1. This library was designed with proprietary modeling software for use as a general screening library. The 30 R1 reagents were phenols, and the 275 R2 reagents were taken from five different reagent classes, giving a variety of product classes in the final library of 8250 potential products. All of the library members were generated from a common intermediate, mesylate (5), which was synthesized efficiently, in bulk, in three steps from N-benzylethanolamine (2). High-throughput chemistry using robotics was carried out to produce the 7907 library members, which were individually characterized by reversed-phase LC/MS analysis.

A bioassay-directed fractionation of cultures of the fungus, Verticillium chlamydosporium, demonstrated nematicidal activity, due mainly to phomalactone. Compared with aldicarb, the lethal activity against Meloidogyne incognita was less, but its activity in suppressing root invasion was similar. The extract also contained monorden.