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 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.
Parker
Michael H
MH
Drug Discovery Division, Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477, USA.
Chen
Robert
R
Conway
Kelly A
KA
Lee
Daniel H S
DH
Luo
Chi
C
Boyd
Robert E
RE
Nortey
Samuel O
SO
Ross
Tina M
TM
Scott
Malcolm K
MK
Reitz
Allen B
AB
D016229:Amyloid beta-Peptides / Q000187:drug effects*; D000975:Antioxidants / Q000494:pharmacology; D052160:Benzothiazoles; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D018360:Crystallography, X-Ray; D005456:Fluorescent Dyes; D006873:Hydroquinones / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry
C471618:5,8-dihydroxy-3-methyl-2-(dipropylamino)-1,2,3,4-tetrahydronaphthalene; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D006873:Hydroquinones; D007202:Indicators and Reagents; D010446:Peptide Fragments; D013764:Tetrahydronaphthalenes; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T; C031927:hydroquinone