Abstract
The diastereoselective hydroxylation of milbemycin A4 (1) at the 13β-position (→2) was performed by cultures of Streptomyces violascens (ATCC 31560). 14, 15-epoxymilbemycin A4 (3) was formed via a parallel reaction as a byproduct. The conversion and the product ratio, 2/3, were improved by the addition of organic solvents. The best results, i.e., 91% conversion with 92% 2 and 8% 3, were obtained by adding 2.5% DMSO to the culture broth. Oxime 7 was also hydroxylated at the 13β-position by S. violascens under similar conditions. In the case of milbemycin A3 (9) and D (10), the main products after treatment with S. violascens were the corresponding 14, 15-epoxides, 13 and 14, respectively.
