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Synfacts 2012; 8(10): 1049
DOI: 10.1055/s-0032-1317203
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Suvorexant

Contributor(s):
Philip Kocienski
Mangion IK, * Sherry BD, Yin J, Fleitz FJ. Merck & Co., Rahway, USA
Enantioselective Synthesis of a Dual Orexin Receptor Antagonist.

Org. Lett. 2012;
14: 3458-3461
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Publication History

Publication Date:
19 September 2012 (online)

 
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Key words

suvorexant - dual orexin receptor antagonists - enzymatic transamination

Significance

Orexins A and B are excitatory neuropeptides that stimulate wakefulness. Suvorexant is a dual orexin receptor antagonist that is in phase III clinical trials for the treatment of insomnia. The key step in the asymmetric synthesis ­depicted is a tandem enzymatic transamination–annulation sequence (F → G → H).


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Comment

A previous synthesis of suvorexant (N. A. Strotman et al. J. Am. Chem. Soc. 2011, 133, 8362) involved an asymmetric Ru-catalyzed reductive amination in the construction of the diazepane ring. The present route benefits from the circumvention of transition-metal catalysis and dichloromethane as solvent.


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