title: 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.
abstract: 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.
authors.affiliation: Bayer CropScience AG, Research Monheim, Global Chemistry Insecticides, Building 6240, Alfred-Nobel-Str. 50, D-40789 Monheim am Rhein, Germany. peter.jeschke@bayercropscience.com
authors.forename: Peter
authors.initials: P
authors.lastname: Jeschke
authors.forename: Achim
authors.initials: A
authors.lastname: Harder
authors.forename: Winfried
authors.initials: W
authors.lastname: Etzel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gau
authors.forename: Axel
authors.initials: A
authors.lastname: Göhrt
authors.forename: Jordi
authors.initials: J
authors.lastname: Benet-Buchholz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Thielking
mesh_terms: 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
chemical_list: D000871:Anthelmintics; D007202:Indicators and Reagents; D011728:Pyridones; D011758:Pyrroles