Non-natural demethylavermectins and process therefor

Claim 1

A compound for preparation of a compound of the formula: wherein the broken line at the 22-23 position represents an optional double bond; R¹ is H or OH and the double bond is absent, or, the double bond is present and R¹ is absent; R is an alpha-branched C₃-C₈ alkyl, alkenyl, alkynyl, alkoxyalkyl or alkylthioalkyl group; a C₅-C₈ cycloalkylalkyl group wherein the alkyl group is an alpha-branched C₂-C₅ alkyl group; a C₃-C₈ cycloalkyl or C₅-C₈ cycloalkenyl group, either of which may optionally be substituted by methylene or one or more C₁-C₄ alkyl groups or halo atoms; or a 3 to 6 membered oxygen or sulfur containing heterocyclic ring which may be saturated, or fully or partially unsaturated and which may optionally be substituted by one or more C₁-C₄ alkyl groups or halo atoms; with the proviso that when R is alkyl, it is not isopropyl or sec-butyl; R² is a disaccharide moiety of the formula where each of R⁴ and R⁵ is hydrogen or methyl, with the proviso that at least one of R⁴ and R⁵ is hydrogen; and R³ is hydrogen or methyl;which comprises aerobically fermenting in the presence of sinefungin with a strain of streptomyces avermitilis which lacks one or both of branched-chain 2-oxo acid dehydrogenase activity and branched-chain amino acid transaminase activity, an aqueous nutrient medium comprising an assimilable source of nitrogen, carbon and inorganic salts and a compound capable of utilization in the biosynthesis of an avermectin.