Synthesis of ¹⁴C‐Labelled Cefclidin (E1040)

Abstract

Cefclidin (E1040), a new injectable cephalosporin with potent antipseudomonal activity, was synthesized labelled with carbon‐14, starting from bromo[1‐14C]acetic acid according to the method illustrated in Scheme 1, 2. [14C] Cefclidin, having a specific activity of 3.43 MBq/mg (water content 15.3%, which was based on water content of non labelled compound prepared by the same procedure), was obtained in 2% overall radiochemical yield, with a radiochemical purity of more than 99.1%.

Preparation of Carbon‐14‐Labeled Compounds via Multi‐Carbon Building Blocks of the [ 14 C]Carbon Dioxide Tree

“…Under similar reaction conditions ethyl½1-14 Cacetate adds to g-butyrolactone to provide b-½1-14 Cacetyl-g-butyrolactone (77) (Figure 6.28), which upon hydrolysis gave 5-chloro-2-[carbonyl-14 C]pentanone (78) (79), which served as a labeled C 5 building block in the synthesis of [5-14 C]farnesylacetic acid (80) 59 .…”

“…This is illustrated in (100), which began with the N-alkylation of isonipecotamide (98) to give N-hydroxyethyl derivative 99. This compound was a late intermediate in the synthesis of [ 14 C]cefclidine (101) 79 . Subsequent a-deprotonation with LDA and intramolecular C-alkylation converted the chloronitrile into (100).…”