Determination of the absolute configurations at stereogenic centers in the presence of axial chirality.
Cephalochromin, a homodimeric naphthpyranone natural product, contains both axial chirality due to the hindered rotation along the biaryl axis and central chirality due to the C-2, C-2' stereogenic centers of the fused pyranone ring. For determining the absolute configurations (ACs) of central chirality elements, different chiroptical spectroscopic methods, namely vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotation (OR), have been used. From these experimental data, in conjunction with corresponding quantum chemical predictions at B3LYP/6-311G* level, it is found that the ECD spectra of cephalochromin are dominated by its axial chirality and are not suitable to distinguish the (aS,2S,2'S) and (aS,2R,2'R) diastereomers and hence to determine the ACs of the central chirality elements. OR signs also did not distinguish the (aS,2S,2'S) and (aS,2R,2'R) diastereomers. On other hand, VCD spectrum of cephalochromin exhibited separate spectral features attributable to axial chirality and stereogenic centers, thereby allowing the determination of both types of chirality elements. This is the first investigation demonstrating that, because of vibrations specific to the studied stereogenic centers, VCD spectroscopy can be used to simultaneously determine the ACs of axial and central chirality elements whenever other chiroptical methods (ECD and OR) fail to report on them.
Polavarapu
Prasad L
PL
Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA. polavarapu@vanderbilt.edu
Jeirath
Neha
N
Kurtán
Tibor
T
Pescitelli
Gennaro
G
Krohn
Karsten
K
D000900:Anti-Bacterial Agents / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry; D002511:Cephalosporins / Q000737:chemistry; D002942:Circular Dichroism; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009904:Optical Rotation; D011789:Quantum Theory; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014732:Vibration
D000900:Anti-Bacterial Agents; D001688:Biological Products; D002511:Cephalosporins; C011417:cephalochromin