Isolation, synthesis and absolute configuration of 4,5-dihydroxypiperines improving behavioral disorder in AlCl3-induced dementia

Bioorg Med Chem Lett. 2021 Jun 15:42:128057. doi: 10.1016/j.bmcl.2021.128057. Epub 2021 Apr 21.

Abstract

A pair of stereoisomers of new 4,5-dihydroxypiperine was isolated from P. retrofractum and showed profound activity on AlCl3-induced dementia. In order to determine their absolute configurations and biological activities, all four possible stereoisomers of 4,5-dihydroxypiperine were synthesized from piperidine by Sharpless asymmetric dihydroxylation and Mitsunobu reaction. Their absolute configurations were established as (4R,5R) (1), (4S,5S) (2), (4S,5R) (3) and (4R,5S) (4) by NMR, optical rotation and CD spectra. It is note that only compound 4 improved behavioral disorder in AlCl3-induced dementia. Accordingly, the pair of stereoisomers isolated from P. retrofractum was determined to be (4S,5S) and (4R,5S)-isomers (2 and 4). The ratio of the epimers was present as 1:0.7 (4:2).

Keywords: 4R,5S-dihydroxypiperine; Alzheimer’s disease; P. retrofractum; asymmetric synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Aluminum Chloride
  • Animals
  • Behavior Therapy
  • Benzodioxoles / chemistry
  • Benzodioxoles / isolation & purification
  • Benzodioxoles / pharmacology*
  • Dementia / chemically induced
  • Dementia / drug therapy*
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Piperaceae / chemistry*
  • Piperidines / chemistry
  • Piperidines / isolation & purification
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / chemistry
  • Polyunsaturated Alkamides / isolation & purification
  • Polyunsaturated Alkamides / pharmacology*
  • Structure-Activity Relationship
  • Zebrafish

Substances

  • Alkaloids
  • Benzodioxoles
  • Piperidines
  • Polyunsaturated Alkamides
  • Aluminum Chloride
  • piperine