Microbial process for preparation of glucuronides of raloxifene

Raloxifene, also known as Evista(R), has recently been approved for the pre vention of osteoporosis. Three glucuronidated compounds: raloxifene-6-glucu ronide, raloxifene-27-glucuronide, and raloxifene-6,27-diglucuronide are kn own metabolites of raloxifene in man. Reference standards of the three gluc uronides were needed for clinical trials. Although chemical routes exist to make the two mono-glucuronides, these routes were unable to provide materi al to meet the needs of clinical trial standards. No chemical route existed to synthesize the di-glucuronide. A bioconversion process using the microo rganism Streptomyces sp NRRL 21489 was identified and scaled up. The biotra nformation products were prepared in a tank fermentation, purified, and cha racterized by UV, LC/MS and NMR spectroscopy.