Details

Autor(en) / Beteiligte

• Schmidt, Burkhard
• Schumacher-Buffel, Ramona
• Thiede, Brigitte
• Schäffer, Andreas

Titel

Synthesis of [1-15N,2-13C]-labeled difloxacin

Ist Teil von

• Monatshefte für Chemie, 2009-10, Vol.140 (10), p.1221-1227

Ort / Verlag

Vienna: Springer Vienna

Erscheinungsjahr

2009

Link zum Volltext

Quelle

SpringerNature Journals

Beschreibungen/Notizen

• The synthesis of [1- 15 N,2- 13 C]-difloxacin, an arylfluoroquinolone antibacterial agent, is reported. As a crucial initial step, the starting materials ethyl 2,4,5-trifluorobenzoylacetate, [formyl- 13 C]-triethyl orthoformate, and [ 15 N]-4-fluoroaniline were reacted to ethyl [ 15 N,3- 13 C]-3-(4-fluoroanilino)-2-(2,4,5-trifluorobenzoyl)acrylate. After cyclization and ester cleavage, the resulting intermediate was reacted with 1-methylpiperazine to [1- 15 N,2- 13 C]-1-(4-fluorophenyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate, i.e., [1- 15 N,2- 13 C]-difloxacin. The overall yield was 62% based on the non-labeled and 43% based on the labeled starting materials (both used in 1.4 molar excess). The product was identified by 1 H-, 13 C-, and 15 N-NMR spectroscopy and by cochromatography (TLC, HPLC) with an authentic reference; its purity (HPLC) was above 98%. Prior to synthesis of [1- 15 N,2- 13 C]-difloxacin, non-labeled difloxacin was synthesized in order to optimize procedures and to identify and characterize all intermediates. Graphical Abstract