SYNTHESIS OF THE BETA-LACTAMASE INDICATORS CEFESONE AND NITROCEFIN

The synthesis of the beta-lactamase indicators Cefesone 4-dinitrostyry l)-7-(phenylacetamido)ceph-3-em-carb oxylic acid] and Nitrocefin 3-(2, 4-dinitrostyryl)-7-(2-thienylacetamido)ceph-3 -em-4-carboxylic acid] f rom tert-butyl l-1-oxo-7-(phenylacetamido)ceph-3-em-4-carboxylate is r eported. Phosphonylation of the latter compound with triphenylphosphin e gave the corresponding phosphonium derivative in 93% yield. Reductio n followed by Wittig coupling with 2,4-dinitrobenzaldehyde gave a 1:12 mixture of E-and Z-isomers in 83% yield. The tert-butyl protecting gr oup was removed with titanium tetrachloride to give Cefesone as the pu re crystalline E-isomer in 63% yield. De-acylation was achieved by enz ymatic hydrolysis in 77% yield. Finally the 2-thienylacetyl side chain was introduced to give crystalline Nitrocefin in 67% yield.