Determination of the absolute configurations of natural products using TDDFT optical rotation calculations: the iridoid oruwacin.
We report the determination of the absolute configuration (AC) of the iridoid natural product oruwacin by comparison of the optical rotations, [alpha] D, of its two enantiomers, calculated using time-dependent density functional theory (TDDFT), to the experimental [alpha] D value, +193. Conformational analysis of oruwacin using density functional theory (DFT) identifies eight conformations which are significantly populated at room temperature. [alpha] 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 [alpha] D values of -193 for the (1 R,5 S,8 S,9 S,10 S)-enantiomer and +193 for the (1 S,5 R,8 R,9 R,10 R)-enantiomer. Comparison of the calculated [alpha] D values to the value of the natural product proves that naturally occurring oruwacin has the AC 1 S,5 R,8 R,9 R,10 R. This AC is opposite to that assigned by Adesogan by comparison of the [alpha] 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 [alpha] D to that of a chemically related molecule can be unreliable and should not be assumed to be definitive.
Stephens
P J
PJ
Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482, USA. pstephen@usc.edu
Pan
J J
JJ
Devlin
F J
FJ
Cheeseman
J R
JR
D001688:Biological Products / Q000737:chemistry*; D039823:Iridoids / Q000737:chemistry*; D015394:Molecular Structure; D032066:Morinda / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D013237:Stereoisomerism
D001688:Biological Products; D039823:Iridoids; C528204:oruwacin