Organic Synthesis Core Facility, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Bioorg Med Chem Lett. 2009 Feb 1;19(3):922-5. doi: 10.1016/j.bmcl.2008.11.117. Epub 2008 Dec 7.
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.
新型光反应性γ-分泌酶抑制剂 2 和 3 的立体选择性合成已经实现。该策略的关键步骤包括α-N-Boc-环氧化物 8 的制备和内酯 14 的实际和立体控制形成。化合物 2 和 3 是有效的γ-分泌酶抑制剂，并且直接与γ-分泌酶的催化亚基早老素-1 相互作用。
