Synfacts 2011(9): 0927-0927  
DOI: 10.1055/s-0030-1260913
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a γ-Secretase Inhibitor

Contributor(s):Philip Kocienski
J. Su*, H. Tang, B. A. McKittrick
Merck Research Laboratory, Kenilworth, USA
Stereoselective Synthesis of C-6 Hydroxy Tricyclic Sulfone as a γ-Secretase Inhibitor
Tetrahedron Lett.  2011,  52:  3382-3385  
Further Information

Publication History

Publication Date:
19 August 2011 (online)


γ-Secretase inhibitors are of interest for the treatment of Alzheimer’s disease. The key step in the synthesis of the target γ-secretase inhibitor is the stereoselective opening of the epoxide E using a (triarylthio)boron reagent F derived from reaction of BH3 with p-chlorobenzenethiol.


The cis stereochemistry in H derives from prior coordination of the (triarylthio)boron reagent to the epoxide oxygen in E followed by epoxide ring opening and intramolecular transfer of an arylthio group to the resultant carbocation G.