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

✍ Scribed by D. Hesk; I. Gunnarsson; S. Hendershot; D. Koharski; P. McNamara; J. L. Schwartz; M. Thonoor; M. Wirth

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 406 KB
• Volume: 42
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199902)42:2<159::aid-jlcr177>3.0.co;2-6

✦ Synopsis

({ }^{3} \mathrm{H}) and ({ }^{14} \mathrm{C})-Sch 27899 have been prepared by fermentation using the Micromonospora carbonacea organism. In the case of ({ }^{3} \mathrm{H})-Sch 27899 , the label was incorporated by a single addition of (100 \mathrm{mCi}) of (70 \mathrm{Ci} / \mathrm{mmole} \mathrm{L-[3} \mathrm{H})-methyl]-methionine to two flasks. For ({ }^{14} \mathrm{C}) Sch (27899,48 \mathrm{mCi}) of (55 \mathrm{mCi} / \mathrm{mmole} \mathrm{L-[{ } ^ { 1 4 } \mathrm { C } \text { -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-[3 (\mathrm{H})-methyl]-methionine and (18.7 %) from L(\left[{ }^{14} \mathrm{C}\right.)-methyl]-methionine. The in vivo stability of label of ({ }^{3} \mathrm{H}) and ({ }^{14} \mathrm{C})-Sch 27899 was determined, with ({ }^{14} \mathrm{C})-Sch 27899 found to be a better choice for use in in vivo metabolism studies.