Assignment of absolute configuration of chiral carboxylic acids via exciton-coupled CD treatment: 4-phenylthioproline as a case study.
The 4-hydroxybenzoate chromophore was used as an exciton reporter group for the assignment of the absolute configuration of a chiral carboxylic acid of pharmaceutical interest, (-)-(2S,4S)-4-phenylthioproline, precursor of the ACE-inhibitor zofenopril. The nondegenerate coupling with the preexisting phenylthio chromophore was observed. A detailed conformational analysis, accomplished by means of (1)H-NMR NOESY and semiempirical PM3 computational methods, and quantitative CD calculations were necessary to substantiate the assignment based on a weak experimental couplet.
Centro di Studio del CNR per le Macromolecole Stereordinate e Otticamente Attive, Dipartimento di Chimica e Chimica Industriale, Pisa, Italy.
Lorenzo
L
Di Bari
Serena
S
Mannucci
Gennaro
G
Pescitelli
Piero
P
Salvadori