Synthesis of 3H and 14C‐SCH 27899 by fermentation and evaluation of in vivo label stability

3H and 14 C-Sch 27899 have been prepared by fermentation using the Micromonospora carbonacea organism. In the case of 3 H-Sch 27899, the label was incorporated by a single addition of 100 mCi of 70Ci/mmole L-[3H-methyl]-methionine to two flasks. For 14 C-Sch 27899, 48 mCi of 55 mCi/mmole L-[14C-methyl]-methionine was added in five aliquots to five flasks over a five day period. Both batches were isolated by solvent extraction, oxidized and purified by column chromatography and hplc. An overall incorporation of 7.8% was found from L-[3H-methyl]-methionine and 18.7% from L-[14C-methyl]-methionine. The in vivo stability of label of 3 H and 14 C-Sch 27899 was determined, with 14 C-Sch 27899 found to be a better choice for use in in vivo metabolism studies.