Synthesis and anthelmintic activity of 7-substituted 3,4a-dimethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2-b]pyridine-6,8(7H)-diones.
The racemic 7-substituted 3,4a-dimethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2-b]pyridine-6,8(7H)-diones represent novel tricyclic compounds with strong in vivo efficacy against the parasitic nematode Haemonchus contortus Rudolphi in sheep. Here we report on the synthesis of tricyclic endo-2,3-dihydro[3,2-b]pyridine-type cycloadducts and describe the separation of the racemic 3,4a-dimethyl-7-ethyl-4a,5a,8a,8b-tetrahydro-6H-pyrrolo[3',4':4,5]furo[3,2]pyridine-6,8(7H)-dione into the enantiomers by HPLC. The absolute configuration of the most anthelmintically active (4aS,5aS,8aS,8bR)-enantiomer was determined by single crystal X-ray analysis using its stable (4aS,5aS,8aS,8bR)-enantiomer-CuCl2 (2:1)-complex.
Jeschke
Peter
P
Bayer CropScience AG, Research Monheim, Global Chemistry Insecticides, Building 6240, Alfred-Nobel-Str. 50, D-40789 Monheim am Rhein, Germany. peter.jeschke@bayercropscience.com
Harder
Achim
A
Etzel
Winfried
W
Gau
Wolfgang
W
Göhrt
Axel
A
Benet-Buchholz
Jordi
J
Thielking
Gerhard
G
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000494:pharmacology; D006189:Haemonchus / Q000187:drug effects*; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology
D000871:Anthelmintics; D007202:Indicators and Reagents; D011728:Pyridones; D011758:Pyrroles