Investigations into the Role of the Decalin Ring System on the Activity of Diterpene-Based β-Lactam Adjuvants

Abstract Recent work from our labs outlined the potential of diterpene-based β-lactam adjuvants against Gram-positive infections. Here, we expand on that work by carrying out a systematic study to elucidate the role of the decalin ring system, with the goal of developing more active scaffolds. To achieve this, new synthetic routes were developed that facilitate more direct analog synthesis relative to the first-generation route. Finally, biological assessment indicates that the decalin system may provide key hydrophobic interactions with the target.