Improved methods of convergent synthesis for peptidomimetic utilizing a chloroalkene dipeptide isostere (CADI) are reported. In this synthesis, Fmoc- or Boc-protected carboxylic acids can be produced from N- and C-terminal analogues corresponding to each amino acid starting material via an Evans syn aldol reaction, followed by a [3.3] sigmatropic rearrangement utilizing the Ichikawa allylcyanate rearrangement reaction. With this strategy, an Fmoc-protected CADI can be directly applied for solid-phase peptide synthesis. Using this approach, we have also identified the CADI-containing cyclo[-Lys-Leu-Val-Phe-Phe-] peptidomimetic, which is a superior inhibitor of amyloid-β aggregation than the parent peptide.

JOURNAL：
The Journal of Organic Chemistry

TITLE：
Development of methods for convergent synthesis of chloroalkene dipeptide isosteres and its application

DOI：
https://doi.org/10.1021/acs.joc.0c03019

Hirokazu TAMAMURA,Ph.D.,Professor
Department of Medicinal Chemistry,
Institute of Biomaterials and Bioengineering,
Tokyo Medical and Dental University(TMDU)
E-mail:tamamura.mr(at)tmd.ac.jp

＊Please change (at) in e-mail addresses to @ on sending your e-mail to contact personnels.