Synthesis and Preliminary Biological Evaluation of Fluorescent Glycofused Tricyclic Derivatives of Amyloid [beta]-Peptide Ligands

Fluorescent glycofused tricyclic compounds were synthesized through the domino conjugate oxa-Michael addition/aldol condensation of 2-hydroxybenzaldehydes with protected 3-oxoglucal by exploiting activation with an organocatalyst. Stereoselectivity was obtained by using (R)-(+)-[alpha],[alpha]-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether as the catalyst. All synthesized compounds presented good optical properties. All compounds were able to bind to synthetic amyloid [beta] 1-42 peptide aggregates and to label amyloid plaques from brain sections of transgenic mice affected with Alzheimer's disease with staining properties comparable to thioflavin T.