New Milbemycins from Streptomyces hygroscopicus subsp. aureolacrimosus: Fermentation, Isolation and Structure Elucidation

Twelve new milbemycins have been isolated and characterized from some strains derived from Streptomyces hygroscopicus subsp. aureolacrimosus SANK 60286 and SANK 60526. The metabolites 1-4 and 9-11 were produced by strain RM28D-688 SANK 60797 as minor products. The metabolites 5-8 were obtained from a broth of strain 57-338 SANK 61796. Strain MK-1391 SANK 62896 was used for the production of metabolite 12. The new metabolites, eight α-class and four β-class compounds, have new structural features. For example, milbemycins α26 and α27, have the 26-hydroxy moiety, and other derivatives (milbemycins α20-23) have different side cnams at the C-26 position from those of milbemycins α11 and α14. In addition, 5-hydroxylmilbemycin β7 (β12), involved in the major biosynthetic pathway of 25-methyl and 25-ethyl milbemycins, was discovered.