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

Abstract

Stereoisomers of 5-(2-allylsulfinyl)-3,4-dimethylthiolane-2-ol, a family of 3,4-dimethylthiolanes of formula CHOS 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 B (CHOS), whose structures we demonstrate have been misassigned. 2D C-C 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 A (CHOS), from extracts of onion ( Allium cepa) and Allium fistulosum, and garlicnin A (CHOS), 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 (CHOS), 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.

Isoalliin-Derived Thiolanes Formed in Homogenized Onion

“…A similar conclusion was recently made by Block et al, who disproved the structure proposed by Nohara’s group , for garlicnins B ( 11a ) isolated from garlic (Allium sativum). It has been shown that these compounds are in fact allyl isomers of onionins A ( 11b , Figure ).…”

“…Several groups of 3,4-dimethylthiolane-based compounds have been found in homogenized onion: i.e., cepadithiolactones A, onionins B and C, and cepathiolanes B and C. These newly discovered groups have significantly extended the number of organosulfur compounds identified in onion previously. Other examples of 3,4-dimethylthiolane-containing species recently found in onion and related Allium species include cepathiolanes A, , onionins A, , and allithiolanes A–I from onion, garlicnins A, , garlicnins B , (syn. ajothiolanes), garlicnins C, , and garlicnins M from garlic and Allium sulfoxides A , from A.…”

Thiolane-type sulfides from garlic, onion, and Welsh onion

“…In relation to the structure of onionin A 1 , we determined the structure of garlicnin B 1 ( 2’ ) isolated from garlicin in 2012. However, in 2018, Block et al corrected the structure of garlicnin B 1 as 3,4-dimethyl-5-allylsulfinylthiolane- 2-ol ( 2 ) [ 25 ] as shown in Fig. 1 .…”

Garlic greening: Pigments biosynthesis and control strategies

“…Thiosulfinates are highly reactive, and thus they easily undergo nonenzymatic reactions yielding numerous sulfur-containing compounds responsible for sensorial attributes and bioactivities of Allium plants (Yoshimoto et al, 2019). Examples are acyclic sulfides, dithiines, and thiolanes that demonstrate bioactive properties similar to those of allicin (Block et al, 2018;Kubec et al, 2018;Martins et al, 2016;Štefanova et al, 2019).…”