Synthesis, resolution and assignment of absolute configuration of trans 3-amino-1-oxyl-2,2,5,5-tetramethylpyrrolidine-4-carboxylic acid (POAC), a cyclic, spin-labelled β-amino acid

摘要: Abstract Racemic trans 3-(9-fluorenylmethyloxycarbonylamino)-1-oxyl-2,2,5,5-tetramethylpyrrolidine-4-carboxylic acid (Fmoc-POAC-OH), prepared by conventional methods, was resolved upon esterification with (aR)-2,2′-dihydroxy-1,1′-binaphthyl. Separation of the obtained diastereomeric monoesters Fmoc-(±)-trans-POAC-O-(aR)-binaphthol crystallization/chromatography, and removal chiral auxiliary saponification aryl ester function furnished both enantiomers (+)-(3R,4R)-Fmoc-POAC-OH (−)-(3S,4S)-Fmoc-POAC-OH. The absolute configuration asymmetric C3, C4 carbons POAC were assigned from induced circular dichroism a flexible biphenyl probe present in terminally protected dipeptide derivatives Boc-Bip-(+)-POAC-OMe Boc-Bip-(−)-POAC-OMe (Bip, 2′,1′:1,2;1″,2″:3,4-dibenzcyclohepta-1,3-diene-6-amino-6-carboxylic acid). This assignment confirmed X-ray diffraction analysis monoester Fmoc-(+)-trans-POAC-O-(aR)-binaphthol, shown to be (aR,3R,4R). Solution synthesis peptides hexamer level, based on (3R,4R)-POAC enantiomer combined (1S,2S)-2-aminocyclopentane-1-carboxylic acid, carried out examine coupling conditions at C- N-termini residue, view further syntheses 3D-structural investigations.