Synfacts 2007(9): 0995-0995  
DOI: 10.1055/s-2007-968915
Polymer-Supported Synthesis
© Georg Thieme Verlag Stuttgart · New York

Photoaffinity Probes for Alzheimer’s Disease

Contributor(s):Yasuhiro Uozumi, Yoichi M. A. Yamada
T. Kan*, Y. Kita, Y. Morohashi, Y. Tominari, S. Hosoda, T. Tomita, H. Natsugari, T. Iwatsubo, T. Fukuyama*
University of Shizuoka and The University of Tokyo, Japan
Convenient Synthesis of Photoaffinity Probes and Evaluation of Their Labeling Abilities
Org. Lett.  2007,  9:  2055-2058  
Further Information

Publication History

Publication Date:
23 August 2007 (online)


A convenient solid-phase synthesis of a variety of photoaffinity probes was achieved by utilizing the Ns (Ns = Nosyl) strategy. Thus, the synthesis of the photoaffinity probe 9 was achieved in 47% overall yield from diazirine 1 and alkyl bromide 2. The carbon-nitrogen bond formation at the side chain was accomplished by the Mitsunobu reaction of the Ns amines (e.g. 4; Ns strategy). By using a similar synthetic route, six photoaffinity probes were prepared. The synthetic probes were evaluated via the labeling ability with the preseniline 1 C-terminal fragments (PS 1 CTFs), and 9 exhibited inihibitory activity of Ab40 (IC50 = 70 nM).


The authors have developed the Ns strategy for the convenient preparation of di- and trialkyl amines (see review below). PS 1 CTFs were identified as therapeutic targets for Alzheimer’s disease. To the authors’ knowledge, there have been no or only few systematic studies on the structure and labeling-ability relationship (SAR) of photoaffinity probes.


T. Kan, T. Fukuyama Chem. Commun. 2004, 353.