The total synthesis of berberine and selected analogues, and their evaluation as amyloid beta aggregation inhibitors

  • Eur J Med Chem. 2021 Apr 5:215:113289. doi: 10.1016/j.ejmech.2021.113289.
Misato Tajiri  1 ,  Ryo Yamada  1 ,  Mayumi Hotsumi  1 ,  Koki Makabe  1 ,  Hiroyuki Konno  2
Affiliations
  • 1. Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan.
  • 2. Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan. Electronic address: [email protected].
PMID: 33611188 DOI: 10.1016/j.ejmech.2021.113289
Abstract

The total synthesis of berberine and selected analogues. And their evaluation as amyloid β (Aβ) aggregation inhibitors is described. The key step in the synthesis, the assembly of the berberine framework, was accomplished using an intermolecular Heck reaction. Berberine analog 17 incorporating a tertiary amine moiety showed good anti Aβ aggregation activity, water solubility, and almost no toxicity to nerve cells.

Keywords
Aggregation inhibition; Alzheimer’s disease; Amyloid beta; Berberine.