Microbial conversion of milbemycins: hydroxylation of milbemycin A4 and related compounds by Cunninghamella echinulata ATCC 9244

Many strains of zygomycetes and actinomycetes were found to convert milbemycin A4 (1a) to 13 beta-hydroxymilbemycin A4 (1b). Among these strains, Cunninghamella echinulata ATCC 9244 had the most efficient 13 beta-hydroxylation ability on milbemycins. In the conversion of milbemycin A3 (2a), 29-hydroxymilbemycin A4 (4a), and 30-hydroxymilbemycin A4 (5a) with this strain, only 13 beta-hydroxylated products were obtained. On the other hand, starting from milbemycin A4 (1a) and 5-ketomilbemycin A4 5-oxime (6a), 13 beta,24- and 13 beta,30-dihydroxy derivatives were also isolated along with 13 beta-hydroxylated products. Similarly, conversion of milbemycin D (3a) and LL-F28249 alpha (8a) gave 13 beta- and 28-hydroxy derivatives (8b and 8c).