【讨论】推荐文章The Danger of Overdependence on NMR Spectroscopy

感谢楼主提供.
文章大部分叙述合成某天然大分子化合物. 叙述本关键核磁命题的内容如下:

Earlier, we described a total synthesis of the structure 3 for ulapualide A, whose stereochemistry we assigned on
the basis of a molecular mechanics study of a hypothetical metal-chelated complex.[1b] The synthetic ulapualide A
showed identical chromatographic behavior, as well as chiroptical and 1H NMR spectroscopic data with those of
naturally derived material, but very small differences were observed in the 13C NMR spectra associated with the
C32-C34 portions of the structures. The stereochemistry of natural ulapualide A (1), determined from an X-ray
analysis of its complex with actin, differs from that of the diastereoisomer 3 at the stereocenters C3, C28, C29,
C30, and C32. This situation makes it all the more bewildering, therefore, as to why the synthetic
diastereoisomer 3 gave 1H NMR spectroscopic and other data which were superimposable on those of the natural
product. We have, therefore, undertaken a conceptually new, second generation, total synthesis of ulapualide
A[4] to resolve any remaining ambiguities with regards to the stereochemistry of the free metabolite, which was
isolated from the egg masses of the nudibranch Hexabranchus sanguineus.[5]
The synthetic ulapualide A displayed 1H and 13C NMR spectroscopic data which were indistinguishable from those
obtained for naturally derived material.[26] Significantly, whereas the synthetic diastereoisomer 3 displayed
small differences in the chemical shifts of the 13C NMR spectra with the natural product for the C32 atom
( =81.0 ppm; cf. =81.8 ppm for natural), the C34 atom ( =26.6 ppm; cf. =27.6 ppm for natural), and for the
C33-methyl group ( =14.2 ppm; cf. =15.5 ppm for natural), the synthetic ulapualide A (1) showed matching chemical shift data for these absorptions, that is, =81.8 (C32), 27.7 (C34), and 15.6 ppm (C33-Me). This total synthesis
of (-)-ulapualide A complements the X-ray studies made by Rayment and co-workers[3b] on an actin-ulapualide A
complex. It also emphasizes how cautious synthetic chemists should be in relying on NMR spectroscopy when
comparing data for some complex natural products and their synthetic counterparts. As this study has shown,
profound changes in the stereochemistry of a natural product (compare 1 and 3) are not always reflected in a
significant way in their NMR spectroscopic data.