Applications of combinatorial chemistry in the agrosciences.

During the past ten years combinatorial chemistry developed from a powerful synthetic methodology, providing large libraries of usually simple new chemical entities, to a comprehensive strategy presently covering a multitude of technologies across the whole workflow from hit generation to lead optimization. Thus combinatorial chemistry had a major impact not only on the pharmaceutical research but also with some delay on the agrochemical research. The agrochemical discovery environment is different from that of the pharmaceutical research in that it relies mainly on whole organism screenings.

PF1022A and related cyclodepsipeptides - a novel class of anthelmintics.

Parasitic nematodes are a major cause of morbidity and mortality in man and also cause widespread loss of food production by infection of livestock. A milestone in the chemotherapy of nematode infections, especially in animals, was the discovery of the avermectins and milbemycins during the 1970s. Since the discovery of these highly active macrolides, reports of potent new classes of anthelmintics have been scarce.

Syntheses of depsipeptide analogues of the insect neuropeptide proctolin.

Four depsipeptide analogues of the insect neuropeptide proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) have been prepared, containing a single ester linkage between Arg(1) and Tyr(2), Tyr(2) and Leu(3), and between Pro(4) and Thr(5), respectively. A didepsipentapeptide containing an ester linkage between Tyr(2) and Leu(3) and between Pro(4) and Thr(5), has also been prepared. The depsipeptide 4 is the first example of a backbone-modified proctolin analogue which shows full myotropic activity.

PF1022A--a novel anthelmintic cyclooctadepsipeptide. Modification and exchange of the N-methyl leucine residues.

The first structure-activity relationships of the anthelmintic cyclooctadepsipeptide PF1022A have been established via a systematic exchange of the leucine residues by a series of related N-alkylated amino acids. The data presented strongly suggest that (L)-N-methyl-leucine is crucial for high in vivo activity.