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Determination of the Absolute Configurations of Natural Products Using TDDFT Optical Rotation Calculations: The Iridoid Oruwacin

2008; American Chemical Society; Volume: 71; Issue: 2 Linguagem: Inglês

10.1021/np070502r

1520-6025

Philip J. Stephens, Jian‐Jung Pan, F. J. Devlin, James R. Cheeseman,

Analytical Chemistry and Chromatography

We report the determination of the absolute configuration (AC) of the iridoid natural product oruwacin by comparison of the optical rotations, [α]D, of its two enantiomers, calculated using time-dependent density functional theory (TDDFT), to the experimental [α]D value, +193. Conformational analysis of oruwacin using density functional theory (DFT) identifies eight conformations which are significantly populated at room temperature. [α]D values of these eight conformations are calculated using TDDFT at the B3LYP/aug-cc-pVDZ//B3LYP/6–31G* level, leading to the conformationally averaged [α]D values of −193 for the (1R,5S,8S,9S,10S)-enantiomer and +193 for the (1S,5R,8R,9R,10R)-enantiomer. Comparison of the calculated [α]D values to the value of the natural product proves that naturally occurring oruwacin has the AC 1S,5R,8R,9R,10R. This AC is opposite to that assigned by Adesogan by comparison of the [α]D of oruwacin to that of the iridoid plumericin. Our results show that the assignment of the AC of a natural product by comparison of its [α]D to that of a chemically related molecule can be unreliable and should not be assumed to be definitive.