Stereoselective synthesis of photoreactive peptidomimetic γ-secretase inhibitors Journal Article
| Authors: | Chun, J.; Yin, Y. I.; Yang, G.; Tarassishin, L.; Li, Y. M. |
| Article Title: | Stereoselective synthesis of photoreactive peptidomimetic γ-secretase inhibitors |
| Abstract: | 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. |
| Keywords: | unclassified drug; drug potency; enzyme activity; drug synthesis; enzyme inhibitors; peptide fragments; cell membrane; platinum derivative; catalysis; molecular conformation; alzheimer disease; synthesis (chemical); carbamates; stereochemistry; stereoisomerism; gamma secretase inhibitor; amyloid precursor protein secretases; gamma secretase; l 685458; endopeptidases; photoreactivity; dipeptides; photochemistry; cells; hydrogenation; benzophenone; lactone; molecular mimicry; aspartic endopeptidases; elimination reaction; aromatic compounds; humans; article; plasma membranes; stereoselective methods |
| Journal Title: | Journal of Organic Chemistry |
| Volume: | 69 |
| Issue: | 21 |
| ISSN: | 0022-3263 |
| Publisher: | American Chemical Society |
| Date Published: | 2004-10-15 |
| Start Page: | 7344 |
| End Page: | 7347 |
| Language: | English |
| DOI: | 10.1021/jo0486948 |
| PROVIDER: | scopus |
| PUBMED: | 15471490 |
| DOI/URL: | |
| Notes: | J. Org. Chem. -- Cited By (since 1996):27 -- Export Date: 16 June 2014 -- CODEN: JOCEA -- Source: Scopus |
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