Synthesis of 5-Keto-5-oxime Derivatives of Milbemycins and Their Activities against Microfilariae

Abstract

Starting from milbemycin D (1), milbemycin A₄ (2) and milbemycin A₃ (3), a series of 5-keto-5-oxime derivatives were synthesized by selective oximation at the α, β-conjugated carbonyl function of the 5-ketomilbemycins (4-6). The activities of the synthesized compounds were studied in dogs naturally infested with microfilariae of Dirofilaria immitis. The 5-keto-5-oximes of milbemycin D (7), A₄ (8) and A₃ (9) had quite high efficacy to control the microfilariae and more potency than their parents, while the 5-O-acyl oximes (11-15) also exhibited high activity.