Ajothiolanes: 3,4-Dimethylthiolane Natural Products from Garlic ( Allium sativum)

Stereoisomers of 5-(2-allylsulfinyl)-3,4-dimethylthiolane-2-ol, a family of 3,4-dimethylthiolanes of formula C9H16O2S2 we name ajothiolanes, were isolated from garlic ( Allium sativum) macerates and characterized by a variety of analytical and spectroscopic techniques, including ultraperformance liquid chromatography (UPLC), direct analysis in real time-mass spectrometry (DART-MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Ajothiolanes were found to be spectroscopically identical to a family of previously described compounds named garlicnins B1-4 (C9H16O2S2), whose structures we demonstrate have been misassigned. 2D 13C-13C NMR incredible natural abundance double quantum transfer experiments (INADEQUATE) were used to disprove the claim of nine contiguous carbons in these compounds, while X-ray absorption spectroscopy (XAS) along with computational modeling was used to disprove the claim that these compounds were thiolanesulfenic acids. On the basis of the similarity of their NMR spectra to those of the ajothiolanes, we propose that the structures of previously described, biologically active onionins A1-3 (C9H16O2S2), from extracts of onion ( Allium cepa) and Allium fistulosum, and garlicnin A (C12H20O2S4), from garlic extracts, should also be reassigned, in each case as isomeric mixtures of 5-substituted-3,4-dimethylthiolane-2-ols. We conclude that 3,4-dimethylthiolanes may be a common motif in Allium chemistry. Finally, we show that another garlic extract component, garlicnin D (C7H12O2S3), claimed to have an unprecedented structure, is in fact a known compound from garlic with a structure different from that proposed, namely, 2( E)-3-(methylsulfinyl)-2-propenyl 2-propenyl disulfide.