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 similar to 4 and 9 similar to 11 were produced by strain RM28D-688 SANK 60797 as minor products. The metabolites 5 similar to 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 alpha-class and four beta-class compounds, have new structural features. For example, milbemycins alpha(26) and alpha(27), have the 26-hydroxy moiety, and other derivatives (milbemycins alpha(20 similar to 23)) have different side chains at the C-26 position from those of milbemycins alpha(11) and alpha(14). In addition, 5-hydroxylmilbemycin beta(7) (beta(12)), involved in the major biosynthetic pathway of 25-methyl and 25-ethyl milbemycins, was discovered.