A Concise Route to Orthogonally Protected Bulgecinine

Bulgecinine is the core structure for inhibitors of the important lytic transglycosylases of bacterial cell-envelope homeostasis. Their central pyrrolidine ring mimics, as the protonated amine, the transient oxocarbenium species of the enzymatic reaction. We report a concise synthesis of protected bulgecinine <b>9</b> (nine linear steps and 12% overall yield). The key step is the vinyl Grignard addition to a nitrone (pyrrolidine-<i>N</i>-oxide) intermediate. Compound <b>9</b> possesses the correct absolute stereochemistry of the three stereogenic centers, validated by an X-ray structure.