A Divergent Route to Eravacycline
Wu-Yan Zhang1, Qinglin Che1, Scott Crawford1
1Tetraphase Pharmaceuticals, Inc. , 480 Arsenal Way, Suite 110, Watertown, Massachusetts 02472, United States.
Abstract:
A convergent route to eravacycline (1) has been developed by employing Michael-Dieckmann cyclization between enone 3 and a fully built and protected left-hand piece (LHP, 2). After construction of the core eravacycline structure, a deprotection reaction was developed, allowing for the isoxazole ring opening and global deprotection to be achieved in one pot. The LHP is synthesized from readily available 4-fluoro-3-methylphenol in six steps featuring a palladium-catalyzed phenyl carboxylation in the last step.
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