Concise Synthesis and Antimicrobial Evaluation of the Guanidinium Alkaloid Batzelladine D

A concise synthesis of the tricyclic guanidinium alkaloid batzelladine D has been accomplished in a sequence of 8 steps from readily available building blocks. Highlights of the synthesis include gram-scale preparation of a late stage intermediate, pinpoint stereocontrol around the tricyclic skeleton and a modular strategy that enables analog generation. A key bicyclic b-lactam intermediate serves to not only control stereochemistry, but also serves as a pre-activated coupling partner to install the ester sidechain. The stereo-controlled synthesis allowed for the investigation of the antimicrobial activity of batzelladine D, demonstrating promising activity that is more potent for non-natural stereoisomers.