Clonostachydiol and helmidiol derivs. - for treating flat worms and round worms in mammals and obtd. by fermentation of Clonostachys cylindrospora or Alternaria sp.

摘要

Clonostachydiol and helmidiol derivs. of formula (I) are new. R1 = -CH2CH2C(CH3)H- or -C(CH3)H-, R2, R3 = H, opt. satd. opt. branched, opt. cyclic 1-20C alkyl ester, opt. substd. aromatic ester or heteroaryl. R2 and R2 = each opt. satd. opt. branched opt. cyclic 1-10C alkyl ester or a benzoyl or aminobenzoyl deriv. substd. on the ring with OH, NH2, 1-10C alkylamino, oxyalkyl, sulphonyl, 1-10C alkylsulphonyl, halogen or thio. Also claimed are the microorganisms Clonostachys cylindrospora DSM 7149 and Alternaria sp. DSM 7150 and their variants and mutants capable of producing (I). Suitable doses are 10-400 mg. in the case of solid dosage forms such as tablets, capsules and suppositories and 10 mg.-1 g. daily in the case of injection solns. 2.50 mg/kg. Clonostachydiol applied s.c. caused 70-90% redn. of H. contortus in sheep. (I) can be prepd. by cultivation of Clonostachys cylindrospora DSM 7149 and/or Alternaria sp. DSM 7150 in a nutrient medium pref. contg. 0.2-5% malt extract, 0.01-0.5% yeast extract, 0.5-2% glucose and 0.01-0.1% (NH4)2HPO4 in the case of DSM-7149 or 0.2-5% soluble starch, 0.2-5% corn starch, 0.2-5.0% glucose, 0.2-5% yeast extract, 0.2-5% corn steep liquor and 0.01-1% CaCO3 in the case of DSM 7150. The cultivation is carried out at 18-30 deg.C and pH 1-7. USE - (I) have biological activity and have antihelminthic activity against Plathelminths (flat worms) and nemathelminths (round worms), esp. against Haemonchus, Trichostrongylus, ostertagia, Cooperia, Chabertia, Strongyloides, Oesophagostomum, Hyostrongylus, Ancylostoma, Ascaris and Heterakis. (I) can thus be used in the prevention and treatment of worms, esp. in mammals, esp. in sheep, goats, cows, horses and pigs.