Yoshihisa Tsukamoto

Synthesis of novel 25-substituted milbemycin A4 derivatives and their acaricidal activity against Tetranychus urticae

Novel 25-substituted milbemycin A4 derivatives were synthesized from 25a-hydroxymilbemycin A4 and 25b-hydroxymilbemycin A4, which had been obtained by the microbial oxidation of milbemycin A4. The acaricidal activity of each synthesized derivative was tested against Tetranychus urticae, and all of the synthesized derivatives showed higher activity than parent milbemycin A4. Some of the derivatives had higher acaricidal activity than milbemycin D, which had higher acaricidal activity than milbemycin A4. Among them, 25b-methylmilbemycin A4 was the most active derivative, with 100% mortality of the mite at a concentration of 1 ppm, and 63% mortality at 0.1 ppm.

Synthesis of Milbemycins α9, α10, α11, α12, α14, α15, α20, α21, α22, α23, α26, α27, Δ2, 3, Δ4, 26-Milbemycins A3, A4 from Milbemycins

Chemical derivation methods to prepare 26-acyloxy and 26-hydroxymilbemycins, which had been reported as natural products, milbemycins alpha9, alpha10, alpha11, alpha12, alpha14, alpha15, alpha20, alpha21, alpha22, alpha23, alpha26, alpha27 from milbemycins A3, A4 were reported. Delta(2,3),delta(4,26)-milbemycins A3, A4, which had also been reported as natural products, were further prepared from milbemycins A3, A4. Their acaricidal activities were also assessed against the organophosphorus-sensitive two-spotted spider mite (Tetranychus urticae) on primary leaves of cowpea plants (Vigna sinesis Savi species) by spraying.

Synthesis of 27-Oxo, 27-Hydroxymilbemycins A3 and A4 and Novel 27-Alkoxymilbemycins A3 and A4 from Milbemycins A3 and A4 and…

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.