jo050740w_si_001.pdf (1.28 MB)
Stereoselective Synthesis of Constrained Azacyclic Hydroxyethylene Isosteres as Aspartic Protease Inhibitors: Dipolar Cycloaddition and Related Methodologies toward Branched Pyrrolidine and Pyrrolidinone Carboxylic Acids
journal contribution
posted on 2005-08-19, 00:00 authored by Stephen Hanessian, Hongying Yun, Yihua Hou, Marina Tintelnot-BlomleyThe synthesis of three vicinally substituted azacyclic carboxylic acids in enantiopure form was
achieved from a common α-amino aldehyde originating from l-leucine. Pyrrolidines and pyrrolidinones were elaborated from α,β-unsaturated γ-hydroxy-δ-amino acids via azomethine ylide 1,3-dipolar addition and conjugate addition/cyclization strategies, respectively. The azacyclic amino
acids were incorporated in a pseudopeptide now encompassing a hydroxyethylene isostere. Low
nanomolar inhibition of BACE1, an enzyme implicated in the cascade of events leading to plaque
formation in Alzheimer's disease, was found with a pyrrolidinone analogue.
History
Usage metrics
Categories
Keywords
hydroxyethylene isostereBranched PyrrolidineBACEAspartic Protease Inhibitorsenantiopure formazacyclic carboxylic acidsStereoselective Synthesisplaque formationConstrained Azacyclic Hydroxyethylene Isosterespyrrolidinone analogueLow nanomolar inhibitionDipolar CycloadditionPyrrolidinone Carboxylic AcidsRelated Methodologies
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC