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Synfacts 2013; 9(8): 0815
DOI: 10.1055/s-0033-1339345
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Eravacycline

Contributor(s):
Philip Kocienski
Ronn M * et al. Tetraphase Pharmaceuticals, Watertown, USA
Process R&D of Eravacycline: The First Fully Synthetic Fluorocycline in Clinical Development.

Org. Process Res. Dev. 2013;
17: 838-845
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Publication History

Publication Date:
18 July 2013 (online)

 
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Key words

eravacycline - tetracycline antibiotics - Michael–Dieckmann annulation

Significance

Eravacycline is a fully synthetic broad-spectrum antibiotic that has completed phase 2 clinical trials for the treatment of multidrug-resistant bacteria. The key step entails the construction of ring C by a tandem Michael addition of arene A to cyclohexenone B followed by a Dieckmann cyclization to afford pentacycle C in 94% yield on a mol scale.


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Comment

The versatile Michael–Dieckmann route to tetracyclines was pioneered by Myers and co-workers (J. Am. Chem. Soc. 2008, 130, 17913). A seven-step multigram-scale synthesis of the crystalline cyclohexenone B has been described: J. D. Brubaker, A. G. Myers Org. Lett. 2007, 9, 3523. Several kilograms of eravacycline were synthesized by the route depicted.


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