Synthesis And Study On The Synthetic Technique Of Doripenem

Doripenem is a new parenteral carbapenem antibiotic with a very potent and broad antibacterial activity, which is used in the therapy of urinary tract infections, respiratory infections, kidney infections, lung infections, and meningitis, endocarditis. It is characterized by 1 β -methy group and a sulfamoylaminomethyl substituted pyrrolidylthio group at C-2 position. It is a cell wall synthesis inhibitor, and shows potency comparable or superior to meropenem against Gram-positive bacteria and potency generally superior to imipenem against Gram-negative bacteria. Doripenem is stable to β -lactamase and hydrolysis by DHP-I without association with cilastatin.At present, Doripenem has been prepared and its Phase III Clinical Trial is under way, while in China, its development is rare.In this assay, we have synthesized Doripenem and its 11 intermediates from two reported synthetic routes, we have chosen a practical one for large-scale synthesis, and meanwhile we have had a study on its synthetic technique and optimized most of the procedures. In addition, we have had some initial study on the quality of the last product.In this article, all the structures of the important intermediates have been confirmed by 1H NMR. When it come to the last product, its structure has been confirmed by the data of 1H NMR, 13C NMR, DEPT, MS and IR.