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Starting from milbemycin D (1), milbemycin A4 (2) and milbemycin A3 (3), a series of 5-keto-5-oxime derivatives were synthesized by selective oximation at the a,/?-conjugated carbonyl function of the 5-ketomilbemycins (4-6). The activities of the synthesized compoundswere studied in dogs naturally infested with microfilariae of Dirofilaria immitis. The 5-keto-5-oximes of milbemycin D (7), A4 (8) and A3 (9) had quite high efficacy to control the microfilariae and more potency than their parents, while the 5-O-acyl oximes (ll-15) also exhibited high activity. The synthesis of the 5-keto-5-oxime derivatives is shown in Scheme 1. The 5-keto intermediates ofmilbemycin A3 (6) and A4 (5) were also isolated from a culture broth of Streptomyces hygroscopicus, and were named 2615 milbemycin J and K, respectively

Eight nitropyridinesulfonamides and pyridinesulfonamide N-oxides as their bioisosteres were prepared and evaluated for anticoccidial activity. Of these compounds, 2-, 4- and 5-nitropyridine-3-sulfonamides and pyridine-2- and -3-sulfonamide N-oxides were found to be active against Eimeria tenella. Thus, the relative positions, ortho or meta, of the substituents in nitropyridine-3-sulfonamides and pyridinesulfonamide N-oxides are important for anticoccidial activity. N-Substituted analogues of 5-nitropyridine-3-sulfonamide were also prepared and optimal anticoccidial activity was attained with the sulfonamide and its lower N-alkyl derivatives. The mode of action of 5-nitropyridine-3-sulfonamide was examined and found to be active in the sporozoite and the first schizogony stages.

Pholipomycin, a new member of the phosphoglycolipid antibiotics, was primarily active against gram-positive bacteria including clinically isolated resistant bacteria. It differed from other members of the antibiotic family as it also demonstrated activity against gramnegative bacteria. Pholipomycin protected mice from infection with Staphylococcus aureus and was nontoxic to mice having an LD50 (i.v.) of 600 mg/kg. Besides possessing antimicrobiol activity, pholipomycin, when administered orally, appeared to promote growth in chickens and pigs.

A number of methyl-2- and 3-nitropyridinecarboxamides have been synthesized. It has been established that the presence of at least one hydrogen atom, adjacent to the NO2 function, is important for anticoccidial activity and introduction of a methyl group to the adjacent position of the CONH2 function sometimes confers enhanced activity. Among the compounds herein, 5- and 6-methyl-2-nitropyridine-4-carboxamides possess optimal anticoccidial activity, being as potent as the parent compound.