Reconsidering the Structures of Tetillapyrone, Nortetillapyrone, Ochraceopyronide, and Rhizoaspergillin A

In this study, we revise the structures of the marine
sponge-derived
pyrone-deoxyribosides tetillapyrone and nortetillapyrone, as well
as the semisynthetic derivative tetillapyrone diacetate, to the nucleosides:
thymidine, deoxyuridine, and thymidine diacetate, respectively. These
revisions are proposed based on reanalysis of reported spectroscopic
and mass spectrometric data, comparisons to authentic standards, and
DFT calculations of NMR chemical shifts. We similarly propose revisions
for the structurally related natural products ochraceopyronide and
rhizoaspergillin A as well as for the semisynthetic derivative rhizoaspergillin
A tripivalate, assigning them as spongouridine, kipukasin O, and kipukasin
O tripivalate, respectively. Notably, the originally proposed structures
of tetillapyrone and rhizoaspergillin A tripivalate were based on
single-crystal X-ray diffraction experiments, widely regarded as the
gold standard technique in small-molecule structure determination.
Our findings highlight some of the key limitations of X-ray crystallographic
analysis and emphasize the importance of cautious data interpretation,
especially when discrepancies arise with spectroscopic or spectrometric
results.