F. Seela, F. Cramer
Mar 1, 1976
Citations
0
Influential Citations
4
Citations
Journal
Bioorganic Chemistry
Abstract
Abstract The synthesis of 4-denitro-4-azido-chloramphenicol is described. Phthalylation of d -threo-(1R:2R)-1-(4-nitrophenyl)-2-amino-1,3-propanediol with N-ethoxy-carbonyl-phthalimide yields d -threo-(1R:2R)-1-(4-nitrophenyl)-2-phthaloylamino-1.3-propanediol. On catalytic hydrogenation, the latter compound is converted to d -threo-(1R:2R)-1-(4-aminophenyl)-2-phthaloylamino-1.3-propanediol, diazotization of which, followed by displacement of the diazonium group by azide ion, gives d -threo-(1R:2R)-1-(4-azidophenyl)-2-phthaloylamino-1.3-propanediol. Hydrazine dephthalylates that compound to give d -threo-(1R:2R)-1-(4-azidophenyl)-2-amino-1.3-propanediol. By esterification of this azide with methyl dichloroacetate d -threo-(1R:2R)-1-(4-azidophenyl)-2-dichloroacetylamino-1.3-propanediol, “4-denitro-4-azido-chloramphenicol” is formed. This substance photolyses on irradiation with uv light to a reactive nitrene, which is expected to form covalent linkages at its ribosomal binding site, and thus, help to elucidate the mode of action of the antibiotic chloramphenicol in protein biosynthesis.