Subscribe to RSS
Synthesis of a γ-Secretase InhibitorContributor(s):Philip Kocienski
Merck Research Laboratory, Kenilworth, USA
Stereoselective Synthesis of C-6 Hydroxy Tricyclic Sulfone as a γ-Secretase Inhibitor
Tetrahedron Lett. 2011, 52: 3382-3385
19 August 2011 (online)
γ-secretase inhibitors - Suzuki-Miyaura coupling - SNAr reaction - epoxide opening
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.