Total Synthesis Route Optimization Of4-AA,a Key Intermediate Of Carbapenems

Carbapenems are known as a type of antibiotic drugs possessing powerful antimicrobial property and wide antimicrobial spectrum. The application of this class of drugs becomes increasingly wide ranging, causing a gradual mounting market demand. However, carbapenems have no existence in natural surrounding, which means there is no possibility of acquiring any of carbapenems by extraction method. As a result, the chemical synthesis routes towards this type of antibiotic have drawn wide attention.4-AA is a key intermediate of synthesis towards carbapenems and dispensable raw material of carbapenems’ total synthesis. Consequently, the market price of4-AA has been rising in recent years. Due to its high difficulty to synthesize, industrialized production is of considerable embarrassment. As a result, eficient synthesis of4-AA with low cost has become the key point of developing carbapenems antibiotics.In this work, we report a route of six steps to synthesize4-AA, starting from L-threonine. By utilizing the temperature, environment, solution and catalyst of those involved reactions like diazotization, C3-C4ring closure, hydroxyl radical protection, deprotection and Baeyer-Villiger oxidation to bring down the synthesis costs and up the output rate of4-AA, we propose a reasonable and rational producing route for industrialized production with high environmental friendliness, facility and efficiency.The output rate of4-AA was25.4%after utilization, and the purity reached up to more than99.5%, characterized by nuclear magnetic resonance (1H-NMR), melting point and optical rotation measurements.