Stephens P J, Pan J J, Devlin F J, Cheeseman J R
Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482, USA.
J Nat Prod. 2008 Feb;71(2):285-8. doi: 10.1021/np070502r. Epub 2008 Jan 23.
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.
我们报告了通过比较环烯醚萜天然产物奥鲁瓦辛两种对映体的旋光度[α]D（使用含时密度泛函理论（TDDFT）计算）与实验[α]D值+193，来确定其绝对构型（AC）。使用密度泛函理论（DFT）对奥鲁瓦辛进行构象分析，确定了在室温下大量存在的八种构象。在B3LYP/aug-cc-pVDZ//B3LYP/6-31G*水平上使用TDDFT计算这八种构象的[α]D值，得到（1R,5S,8S,9S,10S）-对映体的构象平均[α]D值为-193，（1S,5R,8R,9R,10R）-对映体的为+193。将计算得到的[α]D值与天然产物的值进行比较，证明天然存在的奥鲁瓦辛具有AC 1S,5R,8R,9R,10R。该AC与阿德索根通过比较奥鲁瓦辛和环烯醚萜类化合物羽扇豆素的[α]D所指定的AC相反。我们的结果表明，通过将天然产物的[α]D与化学相关分子的[α]D进行比较来确定其AC可能不可靠，不应被认为是确定的。
