American Chemical Society
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Stereoselective Synthesis of Photoreactive Peptidomimetic γ-Secretase Inhibitors

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journal contribution
posted on 2004-10-15, 00:00 authored by Jiong Chun, Ye Ingrid Yin, Guangli Yang, Leonid Tarassishin, Yue-Ming Li
The first asymmetric synthesis of novel, potent photoreactive γ-secretase inhibitors 2 and 3 has been accomplished. Two stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO2-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing γ-secretase activity in the plasma membrane of intact cells.