Synthesis of (-)-5,8-dihydroxy-3R-methyl-2R-(dipropylamino)-1,2,3,4-tetrahydronaphthalene: an inhibitor of beta-amyloid(1-42) aggregation

Bioorg Med Chem. 2002 Nov;10(11):3565-9. doi: 10.1016/s0968-0896(02)00251-1.

Abstract

A concise synthesis of the beta-amyloid(1-42 )aggregation inhibitor (-)-5,8-dihydroxy-3R-methyl-2R-(dipropylamino)-1,2,3,4-tetrahydronaphthalene [(-)-2] has been developed. The key step is a regio- and diastereoselective hydroboration-amination sequence to convert alkene into amine. Enantiomeric resolution was achieved by recrystallization of amine as the dibenzoyl-D-tartaric acid salt. Hydroquinone is a potent inhibitor of the fibrillar aggregation of beta-amyloid as determined in two different assay systems.

MeSH terms

  • Amyloid beta-Peptides / drug effects*
  • Antioxidants / pharmacology
  • Benzothiazoles
  • Chromatography, High Pressure Liquid
  • Crystallization
  • Crystallography, X-Ray
  • Fluorescent Dyes
  • Hydroquinones / pharmacology
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Peptide Fragments / drug effects*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / chemical synthesis*
  • Tetrahydronaphthalenes / pharmacology*
  • Thiazoles / chemistry

Substances

  • 5,8-dihydroxy-3-methyl-2-(dipropylamino)-1,2,3,4-tetrahydronaphthalene
  • Amyloid beta-Peptides
  • Antioxidants
  • Benzothiazoles
  • Fluorescent Dyes
  • Hydroquinones
  • Indicators and Reagents
  • Peptide Fragments
  • Tetrahydronaphthalenes
  • Thiazoles
  • amyloid beta-protein (1-42)
  • thioflavin T
  • hydroquinone