Stereoselective Synthesis of Photoreactive Peptidomimetic ?-Secretase Inhibitors.

ArticleinThe Journal of Organic Chemistry 69(21):7344-7 · November 2004with12 Reads
Impact Factor: 4.72 · DOI: 10.1021/jo0486948 · Source: PubMed

    Abstract

    The first asymmetric synthesis of novel, potent photoreactive gamma-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 PtO(2)-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 gamma-secretase activity in the plasma membrane of intact cells.