Open AccessSubstituted Imidazoline Synthesis: A Diastereo- and Enantioselective aza-Henry Route to a Human Proteasome Modulator
Author(s) -
Daniel J. Sprague,
Jeffrey N. Johnston
Publication year - 2020
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.0c03096
Subject(s) - chemistry , amidine , imidazoline receptor , enantioselective synthesis , adduct , nucleophile , yield (engineering) , proteasome , stereoisomerism , stereochemistry , combinatorial chemistry , catalysis , organic chemistry , biochemistry , pharmacology , medicine , materials science , metallurgy
The first enantio- and diastereoselective synthesis of Tepe's human proteasome modulator is described. Routes to this and other highly substituted chiral imidazolines generally produce racemic material. Key to the route disclosed here is a gram-scale anti -selective aza-Henry reaction of an α-alkyl α-nitro ester nucleophile, catalyzed by a Bis(Amidine) [BAM] chiral proton complex, delivering the key intermediate in high yield as a single stereoisomer. The adduct is reduced to the amino ester and converted to an imidazoline.