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

Abstract

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.