The online assignment of the absolute configuration of natural products: HPLC-CD in combination with quantum chemical CD calculations.
The application of modern online methods, e.g., HPLC-MS/MS and HPLC-NMR, allows the elucidation of constitutions and relative configurations of new natural products directly from crude extracts. To additionally establish the full absolute configurations of such secondary metabolites without the necessity of first isolating the compounds, we have introduced HPLC-CD coupling (CD = circular dichroism) into natural product analysis, taking advantage of the different chiroptical properties of stereoisomers, in particular of enantiomers. In combination with quantum chemical CD calculations this method allows the stereochemical characterization of (even structurally unprecedented) chiral molecules, thus avoiding the--often risky--merely empirical assignment by comparison with the CD spectra of related compounds with known absolute stereostructures, or by other methods such as, e.g., the exciton chirality approach. This review presents the experimental requirements for the hyphenation and the theoretical background of the calculation of UV and CD spectra, which is then exemplified by some recent HPLC-CD applications to the elucidation of absolute configurations of most diverse compounds of mainly natural origin.
Bringmann
Gerhard
G
Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany. bringman@chemie.uni-wuerzburg.de
Gulder
Tobias A M
TA
Reichert
Matthias
M
Gulder
Tanja
T
D016227:Benzoquinones / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002942:Circular Dichroism / Q000379:methods*; D007546:Isoquinolines / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry; D011789:Quantum Theory; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013816:Thermodynamics
D016227:Benzoquinones; D001688:Biological Products; D001713:Biphenyl Compounds; D007546:Isoquinolines; D009281:Naphthalenes; D011166:Porphyrins; C514855:ancisheynine; C522870:ancistrocladinium B; C492703:isoplagiochin C