Convenient synthesis of D‐threo‐[dichloroacetyl 1–¹⁴C] chloramphenicol

Abstract

SummaryA convenient synthesis of chloramphenicol labelled with carbon-14 in the dichloroacetyl group at the 1 position is described. It was prepared as part of a 4-step sequence from [1-14 C] glycine and the product was purified by preparative HPLC.A radiochemical yield of 47% was obtained based on [1-14 C] glycine and the product had a specific activity of 0.47 mCi/mmol. The procedure can be employed for the synthesis of high specific activity [ 14 C] chloramphenicol, labelled at 1, 2 or both the positions of dichloroacetyl group.

Synthesis of Structure and Function Diverse α-D-Diazoacetates, α-D-Diazoacetamides, α-D-Diazoketones, and the Antibiotic α-D-Azaserine

“…Substantiating the general importance of isotope-labelled αdiazoesters (Scheme 1), Unny et al executed the synthesis of 14 C-labelled D-threo-chloramphenicol (1) using, as the key starting material, ethyl [1-14 C]-dichloroacetate (generated by passing Cl 2 through a solution of ethyl [1-14 C]diazoacetate). 7 Johnson required 14 C-labelled γ-cyhalothrin (the unlabelled version is an active constituent of the pyrethroid family of insecticides) for metabolism and environmental studies, a key 14 C-labelled γ-cyhalothrin intermediate employed 1-(1,1-dichloro-2,2,2-trifluoroethyl)-3-methylbut-2-enyl 14 C-diazoester 3 as the starting material. 8 Mezzetti et al generated optically active Nbenzhydryl 13 C-and 15 N-aziridines by reacting N-benzhydryl imines with 13 C-5 or 15 N-6 in the presence of catalytic quantities of RuCl(PNNP)PF 6 [PNNP = (1R,2R)-N,Nbis[2-(diphenylphosphino)benzyl]cyclohexane-1,2-diamine)] allowing them to investigate and probe mechanistic aspects surrounding aziridine formation.…”