Merck + Co., Inc.

Marvin D Schulman

Byron H Arison

Patrick J Doherty

Mary N Omstead

Noel M Young

There are disclosed novel compounds which are derived from 22,23-dihydro avermectin B1 aglycone. The compounds are both isomers of the 27-hydroxy adduct of the substrate avermectin compound that have been glycosylated at the 4' position to yield 4'-O-glucosyl 27-OH avermectin compounds. The compounds and the intermediates used to make them are highly potent antiparasitic, insecticidal and anthelmintic avermectin agents.

Bioconversion products of 27-hydroxy avermectin

Avermectin compounds are glycosylated the 4' and 4'-positions by adding the avermectin compounds to the fermentation medium of Saccharapolyspora erythrea. The outer oleandrose sugar group of the avermectin compound is glycosylated with a glycosyl moiety, specifically a glucose group. In addition, other changes are effected in the avermectin moiety such as selective hydroxylation, epimerization at the 2-carbon and migration of the .DELTA. 3-double bond to a .DELTA. 2-position.

Process for the glycosylation of avermectin compounds

Avermectin aglycones are glycosylated by fermentation in a medium of a non-producing mutant of Streptomyces avermitilis MA-6078. The glycosylation produces the monosaccharide and disaccharide derivatives while leaving the remainder of the molecule intact. The microorganism glycosylates with the .alpha.-L-oleandrose moiety.

Process for the glycosylation of avermectin agylcones

Fermentation of S. erythraea produces the novel avermectin, 28-hydroxy ivermectin aglycone.

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Scotch Plains, NJ, United States of America

Marvin D Schulman