Dihydro avermectin

The catalyst (10 mg) was dissolved in toluene (25 ml) and added under argon to the solution of a mixture (1.1 g) of avermectin Bla (96%) and avermectin Bib (4%) and of m9 °f triphenylphosphine in toluene (25 ml) in a stainless steel autoclave. This starting material was then hydrogenated at 88°C under a hydrogen pressure of 20 bar with stirring of the solution. After 10 hours, HPLC analysis revealed a content of 86% dihydro-avermectin Bla and of 4 % dihydroavermectin Blb, and also of 3% tetrahydroavermectin Bla. 

Metabolism. The drug gets absorbed rapidly, bound to an appreciable extent to plasma protein and excreted ultimately either through the urine or faeces in two forms, namely (i) unchanged invermectin and (a) 3 -0-demethyl-22,23-dihydro-avermectin Bjj, or as dihydroavermectin monosaccharide. Ethanol is found to aggravate the absorption of the drug even upto 100%. 

Ivermectin [22,23 dihydro-avermectin] (Ivomec) 0.05 mg kg biomass twice a week Single in-feed treatment of 0.2 mg kg Johnson Margolis (1993) see Roth et al. (1993)... 

Selective reduction of the 22,23-olefin of avermectin yields the 22,23-dihydro derivative assigned the nonproprietary name ivermectin (18). The stmcture shown depicts the 25-j -butyl derivative [70161 -11-4] but it should be noted that both commercial products contain up to 20% of the 25-isopropyl... 

Methylation of avermectins B and B2 leads to the corresponding derivatives of the A series (49). A procedure involving the oxidation of the 5-methoxy group with mercuric acetate and NaBH reduction of the 5-keto-intermediate allows the conversion of the A to the B components (50). The 23-hydroxy group of the "2" components, after selective protection of the other secondary hydroxy groups, is converted to a thionocarbonate, which can be elirninated to give the 22,23-double bond of the "1" components alternatively it can be reduced with tributyltin hydride to the 22,23-dihydro derivatives (= ivermectins) (51). 

Ivermectin possesses a broad spectrum of antiparasitic activities [51] and is a 22,23-dihydro analogue of the macrocyclic lactone, avermectin B,. Ivermectin is highly effective against microfilariae of O. volvulus at very low doses (50-200/ig/kg) [52] and in comparison with DEC, induces only mild mazzotti reactions and other side-effects. Its effectiveness against D. viteae in M. natalenis [38] and D. immitis [53] is also documented. 

In 1979, as a result of a joint research between the Kitasato Institute, Tokyo, Japan, headed by S. Omura, and Merck, USA, headed by E. O. Stapley, avermec-tins, which have a unique mode of action and potent anthelmintic activity, were discovered in culture mycelia of Streptomyces avermitilis. Ivermectin is a dihydro derivative of avermectin Bj, ensuring its efficacy and safety. It has an extremely broad-spectrum nematocidal activity. 

Ivermectin. 22,23-Dihydroabamectin 22,23-dihydroavermectin B, 22,23-dihydro C-076B, MK-933 Cardomec Eqvalan Heartgard 30 Ivomec Mectizan Zimecterin. Semi-synthetic deriv of abamectin, q. v.. one of the avermectins, q.v Ivermectin contains at least 80% of... 

Component BIt, C H,Pa> S-0-demeihyl-2S-dei l-methyl propyl)-22,23-dihydro-2S-(l-mtthylethyl)avermectin Aw 22,23-dthydroavermectln B therap CAT Anthelmintic (Onchocerca). therap CAT (VET) Anthelmintic, insecticide, acaricide. 

Invermectin is usually extracted from the soil of actinomycete Streptomyces avermitilis, the natural avermectins are 16-membered macrocyclic lactones and is found to be a mixture of 22, 23-dihydro structural analogues of avermectins and B, prepared by catalytic hydrogenation (reduction). In reality, avermectins are members of a family of rather structurally complex antibiotics obtained by fermentative process with the pure isolated strain of S. avermitilis. An intensive screening of cultures for the anthelmintic drugs exclusively from the natural products ultimately gave birth to this wonderful drug. 

First structure-activity relationships relating to crop protection targets were reported by Fisher in 1984 [47]. This study showed that avermectin Bia was somewhat more active then mUbemydn D against Tetranychus urticae, Hdiothis virescens, and Mdoidogyne incognita. As milbemycin D can be viewed as the 22,23-dihydro-13-desoxy derivative of avermectin Bib, this comparison reflects the influence of the disaccharide portion of avermectins on their activity as pesticides. 

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