We developed a practical preparation procedure for K-252a by methylati
ng K-252b on an industrial scale. The water-insoluble K-252a, which wa
s present in the cell mass, was converted to the water-soluble K-252b
Na salt in an alkaline solution. The obtained K-252b was methylated wi
th dimethylsulfate in the presence of potassium carbonate in dimethyla
cetamide. We have already used this method to manufacture 90 kg of K-2
52b from the fermentation broth, and regenerated 65 kg of K-252a from
K-252b.