Synthesis of 27-oxo, 27-hydroxymilbemycins A3 and A4 and novel 27-alkoxymilbemycins A3 and A4 from milbemycins A3 and A4 and their acaricidal activities

27-Oxomilbemycins A3 and A4 and 27-hydroxymilbemycins A3 and A4 were identified as metabolites in soil metabolism studies of milbemycins A3 and A4. Chemical derivation methods were developed to synthesize 27-oxomilbemycins A3 and A4 and 27-hydroxymilbemycins A3 and A4 from milbemycins A3 and A4. In addition, 27-alkoxymilbemycin derivatives were also synthesized from the same precursors. Some of the synthesized compounds displayed satisfactory acaricidal activity against the organophosphorus-sensitive two-spotted spider mite (Tetranychus urticae), but did not have superior activity to corresponding milbemycins A3 and A4.