Process for isolation of romidepsin from fermentation broth and preparation of crystals of romidepsin

A process for the isolation of romidepsin from a fermentation broth which comprises,

• a) extracting the romidepsin from the fermentation broth with an organic solvent and evaporating the solvent to obtain a residue, wherein the organic solvent is selected from the group consisting of isobutyl acetate, isopropyl acetate, ethyl acetate, and toluene;
• b) treating the residue obtained in step a) with an amount of methyl isobutyl ketone or acetonitrile from about 50 to 100 volumes with respect to the content of romidepsin in the residue determined by HPLC to obtain a residue and removing non-dissolved impurities by filtration followed by evaporating the filtrate;
• c) subjecting the residue obtained in step b) to silica gel column chromatography using a silica gel of 60-120 mesh or 230-400 mesh to obtain a product;
• d) treating the product of step c) with an organic solvent selected from the group consisting of methyl isobutyl ketone or acetonitrile to produce a second product;
• and
• e) crystallizing the second product obtained in step d) to obtain romidepsin, wherein romidepsin is characterized as having a purity of greater than 99.5%.