Stereo-controlled synthesis of novel photoreactive gamma-secretase inhibitors.
The stereoselective synthesis of novel photoreactive gamma-secretase inhibitors 2 and 3 has been achieved. Key steps of the strategy involve preparation of alpha-N-Boc-epoxide 8 and formation of lactone 14 in a practical and stereo-controlled fashion. Compounds 2 and 3 are potent gamma-secretase inhibitors and directly interact with presenilin-1, a catalytic subunit of gamma-secretase.
Yang
Guangli
G
Organic Synthesis Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Yin
Ye Ingrid
YI
Chun
Jiong
J
Shelton
Christopher C
CC
Ouerfelli
Ouathek
O
Li
Yue-Ming
YM
D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019921:Biotinylation; D018360:Crystallography, X-Ray / Q000379:methods; D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D004852:Epoxy Compounds / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry; D008956:Models, Chemical; D010777:Photochemistry / Q000379:methods; D053764:Presenilin-1 / Q000737:chemistry
D004151:Dipeptides; D004852:Epoxy Compounds; D007783:Lactones; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases