avermectin-b(1)a and Haemonchiasis

In a critical study, 40 female mixed-breed lambs with experimental infections of Cooperia spp, Trichostrongylus colubriformis, Ostertagia circumcincta, T axei, and Haemonchus contortus were allocated to 8 groups in 1977. Groups 1 and 5 served as controls. Groups 2 to 4 were treated orally with avermectin B1a at dosage levels of 25, 50, and 100 micrograms/kg of body weight, respectively. Groups 6 to 8 were given oral dihydroavermectin B1a at dosage levels of 50, 100, and 200 micrograms/kg, respectively. The lambs were euthanatized and necropsied 6 days after treatment. The compounds were greater than 99% effective at all dosage levels.

Topics: Animals; Anthelmintics; Drug Evaluation; Female; Gastrointestinal Diseases; Haemonchiasis; Intestinal Diseases, Parasitic; Ivermectin; Lactones; Ostertagiasis; Sheep; Sheep Diseases; Trichostrongyloidiasis; Trichostrongylosis

Avermectins A2a, B1a, and B2a (1, 2, and 3) were acetylated to give 4"- and 23-acetates 4 and 5 and 4",23-diacetate 6 from 1, the 4"-and 5-acetates 7 and 8 and 4",5-diacetate 9 from 2, and triacetate 10 from 3. Structure proof by 300-MHz 1H NMR and mass spectral fragmentation is discussed for 10. Forcing acetylation conditions generated from both 1 and 3 the identical aromatic diacetate 11. Good anthelmintic activities in gerbils and sheep for 4"-acetylated derivatives 4 and especially 7 prompted the preparation of additional 4"-acylated derivatives of 2 with pivaloyl, n-octanoyl, succinoyl, carbamoyl, dimethylcarbamoyl and N-acetylglycyl substituents, prepared from the 5-O-tert-butyldimethylsilyl-protected intermediate 12. Other key intermediates were the trichloroethyoxysuccinoyl derivative 18 and 4-nitrophenyl carbonate 21. Anthelmintic activities against Trichostrongylus colubriformis in gerbils comparable in potency to the natural product 2 are shown by the more polar substituted derivatives 20, 23, and 27. Substitution of the 5-hydroxy group or its loss due to aromatization results in drastically reduced anthelmintic potency.

Topics: Animals; Anthelmintics; Chemical Phenomena; Chemistry; Gerbillinae; Haemonchiasis; Ivermectin; Lactones; Ostertagiasis; Sheep; Trichostrongylosis