A Concise Route to Orthogonally Protected Bulgecinine
Qiuyun Yang1, Pradip Shit1, Van T Nguyen1
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Abstract:
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 9 (nine linear steps and 12% overall yield). The key step is the vinyl Grignard addition to a nitrone (pyrrolidine-N-oxide) intermediate. Compound 9 possesses the correct absolute stereochemistry of the three stereogenic centers, validated by an X-ray structure.
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