Synthesis and anthelmintic activity of substituted (R)-phenyllactic acid containing cyclohexadepsipeptides.
The substituted (R)-phenyllactic acid containing cyclohexadepsipeptides (CHDPs) represent novel enniatin derivatives with strong in vivo activities against the parasitic nematode Haemonchus contortus Rudolphi in sheep. 2D NMR spectroscopic analysis revealed for the substituted (R)-phenyllactic acid containing CHDPs one major conformer with an unsymmetrically folded conformation lacking a cis-amide bond. A correlation between the substitution pattern and its anthelmintic activity was found. Here we report on a simple total synthetic pathway of the precursor for this particular type of CHDPs and an efficient modification of the benzylic side chain (R-PhLac(2)).
Jeschke
Peter
P
Bayer CropScience AG, Research & Development, Chemistry Insecticides, Monheim am Rhein, Germany. peter.jeschke@bayercropscience.com
Benet-Buchholz
Jordi
J
Harder
Achim
A
Etzel
Winfried
W
Schindler
Michael
M
Gau
Wolfgang
W
Weiss
Hans-Christoph
HC
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D047630:Depsipeptides / Q000737:chemistry; D007773:Lactates / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry; D011487:Protein Conformation; D012756:Sheep / Q000469:parasitology*
D000871:Anthelmintics; D047630:Depsipeptides; D007773:Lactates; D010455:Peptides; D010456:Peptides, Cyclic; C100264:enniatins; C017648:3-phenyllactic acid; D019344:Lactic Acid