Synthesis and anthelmintic activity of cyclohexadepsipeptides with (S,S,S,R,S,R)-configuration.
The (S,S,S,R,S,R)-configurated cyclohexadepsipeptides (CHDPs) represent novel enniatin derivatives with strong in vivo activity against the parasitic nematode Haemonchus contortus Rudolphi in sheep. 2D NMR spectroscopic analysis revealed for the major conformation the asymmetric conformer, containing a cis-amide bond between C(alpha) protons of neighbouring 2-hydroxy-(S)-carboxylic acid and N-methyl-(S)-amino acid. The absolute configuration of the novel CHDPs was determined by X-ray crystallography. A correlation between the major conformer and its anthelmintic activity was found. Here, we report on a simple total synthetic pathway for this particular type of CHDPs.
Jeschke
Peter
P
Bayer CropScience AG, Research Monheim, Global Chemistry Insecticides, Building Q18, D-51368 Leverkusen, Germany. peter.jeschke@bayercropscience.com
Benet-Buchholz
Jordi
J
Harder
Achim
A
Etzel
Winfried
W
Schindler
Michael
M
Thielking
Gerhard
G
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000494:pharmacology*; D006189:Haemonchus / Q000187:drug effects* / Q000254:growth & development; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D012756:Sheep; D013237:Stereoisomerism
D000871:Anthelmintics; D010456:Peptides, Cyclic