Abstract

In 1976 scientists at the Merck Corporation discovered a complex of eight closely related natural products, subsequently named avermectins A_1a through B_2b, in a culture of Streptomyces avermitilis MA-4680 (NRRL8165) originating from a soil sample collected at Kawana, Ito City, Japan and isolated by the Kitasato Institute. Designated A_1a (C₄₉H₇₄O₁₄), A_1b (C₄₈H₇₂O₁₄), A_2a (C₄₉H₇₆O₁₅), A_2b (C₄₈H₇₄O₁₅), B_1a (C₄₈H₇₂O₁₄), B_1b (C₄₇H₇₀O₁₄), B_2a (C₄₈H₇₄O₁₅), and B_2b (C₄₇H₇₂O₁₅), they are among the most potent anthelmintic, insecticidal, and acaricidal compounds known. Two avermectins, abamectin (the avermectin B₁) and ivermectin, which is saturated at C-22–C-23, have been commercialized to date. Avermectin B₁ is the most effective of the avermectin family of natural products against agriculturally important insects and mites. Ivermectin is active against two significant phyla of animal parasite: the Nemathelminthes or nematodes (roundworms) and the Arthropoda (insects, ticks, and mites). Avermectins are highly lipophilic substances and dissolve in most organic solvents. Avermectin B₁ and ivermectin both contain two secondary and one tertiary hydroxy group. The two secondary alcohols are readily acetylated with acetic anhydride in pyridine. Avermectin B₁ and ivermectin have two secondary hydroxy groups susceptible to oxidation to the corresponding ketones. Ivermectin (,23—dihydroavermectin B₁) is obtained by catalytic reduction of avermectin B₁. Methylation of avermectins B₁ and B₂ leads to the corresponding derivatives of the A series. The worldwide acceptance of ivermectin in livestock production and health care of companion animals has made it the largest selling animal health drug. Abamectin is in commercial use as an agricultural pesticide and its applications are continuing to expand.