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Synfacts 2007(10): 1010-1010  
DOI: 10.1055/s-2007-968954
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a γ-Secretase Inhibitor

Contributor(s): Philip Kocienski, Indu Dager
J. P. Scott*, D. R. Lieberman*
Merck Sharp & Dohme Research Laboratories, Hoddesdon, UK and Merck Research Laboratory, Rahway, USA
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Publication History

Publication Date:
07 November 2007 (online)

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Significance

γ-Secretase is an enzyme responsible for the accumulation of the Ab protein associated with Alzheimer’s disease. This multikilogram-scale synthesis of a γ-secretase inhibitor features a diastereoselective conjugate reduction of α,β-unsaturated aldehyde E, establishing the cis stereochemistry with excellent selectivity. For another large-scale synthesis of this same inhibitor by the Merck group, see: J. Org. Chem. 2007, 72, 4864 and Synfacts 2007, 1009.