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

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 res...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2002-11, Vol.10 (11), p.3565
Main Authors: Parker, Michael H, Chen, Robert, Conway, Kelly A, Lee, Daniel H S, Luo, Chi, Boyd, Robert E, Nortey, Samuel O, Ross, Tina M, Scott, Malcolm K, Reitz, Allen B
Format: Article
Language:English
Subjects:
Amyloid beta-Peptides - drug effects
Antioxidants - pharmacology
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
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Summary: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.
ISSN:0968-0896
DOI:10.1016/S0968-0896(02)00251-1