ABSTRACT
A catalytic asymmetric total synthesis of avibactam and relebactam, two marketed diazabicyclooctane (DBO) ß-lactamase inhibitors (BLIs), has been accomplished. An important feature of this study is the creation of a stereogenic center by using Rh-catalysed asymmetric hydrogenation, affording the crucial α-amino acid ester derivative with high-level enantiocontrol (99% ee). Furthermore, the adoption of flow technologies for the assembly of a majority of intermediates significantly achieves a faster preparation and greater synthetic efficiency than corresponding batch procedures.
Subject(s)
Anti-Bacterial Agents , beta-Lactamase Inhibitors , Amino Acids , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/chemistry , Azabicyclo Compounds/pharmacology , Esters , Microbial Sensitivity Tests , beta-Lactamase Inhibitors/chemistry , beta-Lactamase Inhibitors/pharmacology , beta-Lactamases/chemistryABSTRACT
We disclose an asymmetric total synthesis of prostaglandin C2 TBS ether, a derivative of an extremely sensitive natural prostaglandin C2. The key to the synthesis is a SmI2-mediated ketyl-enoate reaction that leads to the formation of the functionalized cyclopentane ring with high-level stereochemical control. Access to the crucial alkene system is realized late in the synthesis by the implementation of a Grignard addition/dehydration/metathesis sequence.
