Synthesis of potential γ-lactam antibiotics

Synthesis of Optically Active Constrained 2-Substituted Norstatines: A Straightforward Application of Seebach's “SRS” Synthetic Principle

“…In fact, the treatment of 18 and 19 with TFA in anhydrous conditions favored a sequential deprotection of the N -BOC group with the formation of γ-aminobutyric acid derivatives and their spontaneous cyclization to the corresponding γ-lactams (2-pyrrolidones) (2 S ,5 R ,1‘ S )- 29 and (2 S ,5 R ,1‘ R )- 30 , respectively (Scheme ) . Conformationally constrained 2-pyrrolidinones, bearing a quaternary stereogenic center, are found in biologically active molecules, such as inhibitors of proteases and cholesterol absorption, antibiotics, and GABAergic agonists . In our case, these heterocycles are substituted in various positions with precise configurations and are conformationally constrained in a spirocyclic γ-lactam structure as in the agonist GBP-L …”