Optimal Synthesis of Benzodiazepine Glucuronide

Benzodiazepines are in clinical use as antianxiety agents and are controlled substances. Prolonged use may be habit forming. Benzodiazepine abuse is a widespread problem. There is a practical need to screen for the presence of benzodiazepines and their metabolites. Oxazepam glucuronide is the final metabolite of oxazepam and related benzodiazepines in humans and other species. It may be used in the area of drug screening to establish a protocol which will be simpler, faster and more reliable than the method in current use which requires a hydrolysis step. This project proposes to explore the chemical synthesis of oxazepam glucuronide. The synthesis research will include a. preparation of the proper protected sugar moieties, b. coupling reactions between oxazepam and the protected sugar moieties, and c. conversion of coupling compounds into oxazepam glucuronide. The success of the proposed project will provide a new commercial product for forensic chemistry and will lead to the establishment of a new testing method which will have obvious advantages over the present hydrolysis- extraction method. The knowledge from the successful research will be useful for the synthesis of glucuronides of benzodiazepines and other drugs.