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Allithiolanes - Nine Groups of a Newly Discovered Family of Sulfur Compounds Responsible for the Bitter Off-Taste of Processed Onion
Abstract
The compounds responsible for the bitter off-taste of processed onion (Allium cepa) were studied. Using a series of sensory-guided HPLC fractionations, the existence of nine groups of hitherto unknown sulfur compounds has been revealed. On the basis of spectroscopic data (MS, NMR, IR), it was found that these compounds, trivially named allithiolanes A−I, are members of a large family of structurally closely related derivatives of 3,4-dimethylthiolane S-oxide with the general formulas of CxHyO2S4, CxHyO3S5, or CxHyO4S6 (x = 10−18, y = 18−30). The presence of multiple stereoisomers was observed for each group of allithiolanes. Allithiolanes possess an unpleasantly bitter taste with detection thresholds in the range of 15−30 ppm. Formation pathways of these newly discovered sulfur compounds were proposed.
... Thiosulfinates formed from sulfenic acids are also highly reactive species and undergo further spontaneous reactions including [3,3]-sigmatropic rearrangement, intramolecular cycloaddition, the Diels-Alder reaction, and the nucleophilic attack of sulfenic acid or other small sulfur-containing compounds to generate a variety of sulfur-containing compounds. The formed compounds include acyclic sulfides, dithiines, and thiolanes, to most of which the various bioactivities of Allium plants are attributable ( Fig. 7; Block, 2010;Nohara et al., 2017;Block et al., 2018;Kubec et al., 2018). ...
... Thiolane-type cyclic sulfides are spontaneously generated from thiosulfinates (Nohara et al., 2017;Block et al., 2018;Kubec et al., 2018). Among them, onionin A 1 , which was isolated from onions, shows promising anticancer activity by modulating macrophage polarization (El-Aasr et al., 2010). ...
S-Alk(en)ylcysteine sulfoxides are sulfur-containing natural products characteristic of the genus Allium. Both the flavor and medicinal properties of Allium plants are attributed to a wide variety of sulfur-containing compounds that are generated from S-alk(en)ylcysteine sulfoxides. Previous radiotracer experiments proposed that S-alk(en)ylcysteine sulfoxides are biosynthesized from glutathione. The recent identification of γ-glutamyl transpeptidases and a flavin-containing S-oxygenase involved in the biosynthesis of S-allylcysteine sulfoxide (alliin) in garlic (Allium sativum) provided insights into the reaction order of deglutamylation and S-oxygenation together with the localization of the biosynthesis, although the rest of the enzymes in the pathway still await discovery. In intact plants, S-alk(en)ylcysteine sulfoxides are stored in the cytosol of storage mesophyll cells. During tissue damage, the vacuolar enzyme alliinase contacts and hydrolyzes S-alk(en)ylcysteine sulfoxides to produce the corresponding sulfenic acids, which are further converted into various sulfur-containing bioactive compounds mainly via spontaneous reactions. The formed sulfur-containing compounds exhibit bioactivities related to pathogen defense, the prevention and alleviation of cancer and cardiovascular diseases, and neuroprotection. This review summarizes the current understanding of the occurrence, biosynthesis, and alliinase-triggered chemical conversion of S-alk(en)ylcysteine sulfoxides in Allium plants as well as the impact of S-alk(en)ylcysteine sulfoxides and their derivatives on medicinal, food, and agricultural sciences.
... Waste streams such as stalk and petiole have the lowest shallot flavor, which helps them to get better sensorial acceptability. Shallot flower found to be pungent may be due to containing a high amount of sulfur compounds which when comes in contact with air forms compounds such as allithiolanes imparting bitter taste [40]. This may be the reason for the bitter taste in cookies substituted with shallot flower. ...
Shallot harvesting and processing produce various waste streams, and the current study aims to investigate the effects of shallot bio-waste powder (SWP) substitution on different flour properties. Increased SWP to 50% substitution of stalk and petiole showed a rise in swelling capacity (43.33%) and water absorption (342.22%), and oil absorption (320.73%), respectively. Foaming capacity improved from 48.00% in control to 60.26% in 30% flower substitution and further decreases to 51.28% at 50%. Pasting properties reduced at higher SWP substitution and the highest drop in peak viscosity was observed at Stalk-50 (457.33 cP). Subsequently, developed functional cookies showed enhanced fiber, ash, total phenol, and total flavonoids with 3, 2, 7, and 5 fold, respectively. Cookies developed with higher substitution were of darker color and higher hardness and fracturability. Sensory evaluation with fuzzy analysis revealed better acceptance for stalk and petiole (10%) and peel (5%) of final cookies with elevated nutritional value.
... 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). ...
Greening is a major problem for garlic's quality. This phenomenon leads to discoloration of the product and is directly related to the alliinase-catalyzed conversion of isoalliin into 1-propenyl-containing thiosulfates. Garlic crushing, refrigeration, and storage in normal atmosphere, as well as in the presence of monocarboxylic acids, are established the main factors that promote its greening. In last decades, the study of biochemical pathway of this phenomenon has allowed to effectively understand the main steps and key enzymes involved, and to identify optimum conditions for chemical and enzymatic reactions leading to discoloration. These findings have, in some cases, determined the development of new tools for the control of garlic greening on large scale. After providing an updated description of the biochemistry of green pigments produced in garlic, this review reports an overview on the strategies for controlling discoloration of garlic at industrial level.
... [3,3]-Sigmatropic rearrangement of 2b gives 2c, which then undergoes intramolecular 1,3-dipolar [2 + 3] cycloaddition giving 3. Compounds 6b and 6c, also reported in extracts of LFS-suppressed onions, may originate from nucleophilic attack of H 2 S and H 2 S 2 , respectively, on 3. Compound 6d, structurally related to 4, 5, and 6a−c and recently reported to be present in extracts of ordinary onions, is thought to be formed from 1 by a more complex sequence of steps. 9 Cepathiolanes 4 were isolated as mixtures of tautomerically interconvertable stereoisomers. Interestingly, the antiplatelet activity measured by the IC 50 value for in vitro inhibition of cyclooxygenase-1 (COX-1) for 4 was 2 orders of magnitude smaller than the corresponding value for aspirin, a potent antiplatelet coagulation agent that inhibits COX-1. ...
Stereoisomers of 5-(allylsulfinyl)-3,4-dimethyltetrahydrothiolane-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 ultra performance liquid chromatography (UPLC), direct analysis in real time-mass spectrometry (DART-MS), and 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. INADEQUATE NMR methods were used to disprove the claim of nine contiguous carbons in these compounds, while X-ray atomic spectroscopy (XAS) along with computational modeling was used to disprove the claim that these compounds were thiolanesulfenic acids. Based on the similarity of their NMR spectra to those for the ajothiolanes, we propose that the structures of previously described, biologically active onionins A1-3 (C9H16O2S2), from extracts of onion 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.
As an important quality determinant of Toona sinensis, the unique aroma largely impacts the purchasing behavior of consumers. However, the underlying formation mechanism of the characteristic aroma of T. sinensis remains poorly understood. In this work, integrative volatile/nonvolatile compounds profiling and RNA sequencing were used to characterize six T. sinensis cultivars. Volatile sulfur compounds (VSCs) and terpenoids were the main volatile organic compounds (VOCs) in T. sinensis, accounting for 36.95-67.27% and 17.75-31.36% of the total VOC content, respectively. Notably, the VOCs originated from terpenoid biosynthesis, and the degradation of unsaturated fatty acids (UFAs) played important roles in reconciling the irritating odor of VSCs. The above differential metabolic profiles are the main sources of the specific aroma of different T. sinensis cultivars. Furthermore, 13 volatile organic compounds were identified as potential biomarkers to distinguish these T. sinensis cultivars by chemometric analysis. Based on the analysis of transcriptomic datasets, the potential biosynthetic pathways of the key VSCs were firstly confirmed in T. sinensis. It was found that 1-propenylsulfenic acid is a crucial precursor in the formation of characteristic VSCs in T. sinensis. Additionally, two potential mechanisms were proposed to explain the differences of the key VSCs among six T. sinensis cultivars. These results provide theoretical guidance for improving the aroma quality of T. sinensis.
Sulfur-containing compounds, such as cyclic compounds with a vinyl sulfane structure, exhibit a wide range of biological activities including anticancer activity. Therefore, the development of efficient strategies to synthesize such compounds is a remarkable achievement. We have developed a unique approach for the rapid and modular preparation of nature-inspired cyclic and acyclic sulfur-containing compounds using thioacrolein, a naturally occurring chemically unstable intermediate. We constructed thiopyranone derivatives through the regioselective sequential double Diels-Alder reaction of thioacrolein produced by allicin, a major component in garlic, and two molecules of silyl enol ether as the diene partner. The cytotoxicity toward cancer stem cells of the thiopyranones was equal to or higher than that of (Z)-ajoene (positive control) derived from garlic, and the thiopyranones had higher chemical stability than (Z)-ajoene.
The formation of pigment precursors was investigated systematically using green models containing arginine, lysine, alanine, glycine, serine, tyrosine, glutamic acid, and aspartic acid, respectively. Pigment precursor and blue pigments during garlic greening were investigated using ultra-performance liquid chromatography and tandem high-resolution mass spectrometry with a quadrupole time-of-flight analyser (UPLC–ESI-Q-TOF-MS). The intermediate products during the formation of a pigment precursor with a 3-oxopropenyl side chain were tentatively identified. N-substituted 3,4-dimethylpyrrole pigment precursors were found to react with 2-propenesulfenic acid first, and the propenesulfenic acid side-chain decomposed to a 3-oxopropenyl side chain which provided a hypothesis of the formation pathway. Density functional theory calculations combined with the experimental results led to the conclusion that the primary amino group located on the α-carbon reacted with 3,4-dimethylbutanedithial S-oxide to form pigment precursors. In contrast, the amino group in the amino acid R group did not participate in pigment precursors formation. The R-groups of amino acids containing hydroxyls or carboxyl groups have influential roles in the stability of N-substituted 3,4-dimethylpyrrole pigment precursors. In contrast to a previous report, larger R-groups made a more outstanding contribution to the production of blue pigments.
Secondary metabolites isolated from bioactive extracts of natural sources iteratively pioneer the research in drug discovery. Modern medicine is often inspired by bioactive natural products or the bio-functional motifs embedded in them. One of such consequential bio-functional motifs is the thiolane unit. Thiolane-based bioactive organic compounds have manifested a plethora of astonishing biological activities such as anti-viral, anti-cancer, anti-platelet, α-glucosidase inhibition, anti-HIV, immunosuppressive and anti-microbial activities which renders them excellent candidates in drug discovery. Hence, to scale up the accessibility of thiolane-based therapeutics its chemical syntheses is essential and in addition; a sneak peek in its biosynthesis would give a perspective for developing biomimetic syntheses. This review highlights the development of important thiolane-based therapeutics such as (i) Nuphar sesquiterpene thioalkaloids (ii) Thiosugar sulphonium salts from Salacia sp. (iii) Albomycins (iv) Thiolane-based therapeutics from Allium sp. (v) 4′-thionucleosides summarizing various synthetic strategies, biosynthesis and biological activity studies, covering literature till 2021. We anticipate that this review will inspire chemists and biochemists to take up the challenges encountered in the synthesis and development of thiolane-based therapeutics.
Sulfur is unusual in that it is a mineral that may be taken into the body in both inorganic and organic combinations. It has been available within the environment throughout the development of lifeforms and as such has become integrated into virtually every aspect of biochemical function. It is essential for the nature and maintenance of structure, assists in communication within the organism, is vital as a catalytic assistant in intermediary metabolism and the mechanism of energy flow as well as being involved in internal defense against potentially damaging reactive species and invading foreign chemicals.
Recent studies have suggested extended roles for sulfur-containing molecules within living systems. As such, questions have been raised as to whether or not humans are receiving sufficient sulfur within their diet. Sulfur appears to have been the “poor relation” with regards to mineral nutrition. This may be because of difficulties encountered over its multifarious functions, the many chemical guises in which it may be ingested and its complex biochemical interconversions once taken into the body. No established daily requirements have been determined, unlike many minerals, although suggestions have been proposed. Owing to its widespread distribution within dietary components its intake has almost been taken for granted. In the majority of individuals partaking of a balanced diet the supply is deemed adequate, but those opting for specialized or restrictive diets may experience occasional and low-level shortages. In these instances, the careful use of sulfur supplements may be of benefit.
Two novel bisthiolane polysulfides (compounds 1 and 2), trivially named thiolanotrisulfide and thiolanotetrasulfide, were isolated from a reaction model of tearless onion (in which lachrymatory factor synthase is suppressed), and the presence of another novel bisthiolane polysulfide (3), trivially named thiolanopentasulfide, was confirmed. On the basis of spectroscopic and mass spectrometric analyses, it was found that these bisthiolane polysulfides were bis(5-hydroxy-3,4-dimethylthiolan-2-yl)-tri/tetra/pentasulfide with the general formulas of C12H22O2S5 (tri-), C12H22O2S6 (tetra-) and C12H22O2S7 (penta-), and they were confirmed to exist in authentic tearless onion juice. Thiolanotrisulfide (1) and thiolanotetrasulfide (2) inhibited cyclooxygenase-1 activity with IC50 values of 720 ± 78 and 464 ± 48 μM respectively, compared with 3282 ± 188 μM for aspirin.
Several families of 3,4-dimethylthiolane-based compounds spontaneously formed upon cutting of onion (Allium cepa) were studied. We report the isolation of the first known example of a naturally-occurring dithiolactone, 5-hydroxy-3,4-dimethylthiolane-2-thione (cepadithiolactone A, C6H10OS2). Furthermore, on the basis of conceivable spectroscopic evidence (MS, NMR, IR), we could disprove the structure previously proposed for onionin A (C9H16O2S2), which is shown to be in fact (E)-3,4-dimethyl-5-(1-propenylsulfinyl)thiolane-2-ol. The identification of hitherto unknown methyl- and propyl-homologues of onionin A (dubbed onionins B and C, respectively) is also reported. Furthermore, the existence of the methyl- and propyl-homologues of cepathiolanes A (C9H16O2S3), trivially named cepathiolanes B and C, respectively, has been newly revealed. Organoleptic properties of these 3,4-dimethylthiolanes and their role in the formation of the pink discoloration of processed onion were also evaluated.
The onion lachrymatory factor (LF) is produced from trans-S-1-propenyl-L-cysteine sulfoxide (PRENCSO) through successive reactions catalyzed by alliinase (EC 4.4.1.4) and lachrymatory factor synthase (LFS), and is responsible for the tear inducing-property and the pungency of fresh onions. We developed tearless, non-pungent onions non-transgenically by irradiating seeds with neon-ion at 20 Gy. The bulbs obtained from the irradiated seeds and their offspring bulbs produced by selfing were screened by organoleptic assessment of tear-inducing property or HPLC analysis of LF production. After repeated screening and seed production by selfing, two tearless, non-pungent bulbs were identified in the third generation (M3) bulbs. Twenty M4 bulbs obtained from each of them showed no tear-inducing property or pungency when evaluated by 20 sensory panelists. The LF production levels in these bulbs were approximately 7.5-fold lower than those of the normal onion. The low LF production levels were due to reduction in alliinase activity, which was a result of low alliinase mRNA expression (less than 1% of that in the normal onion) and consequent low amounts of the alliinase protein. These tearless, non-pungent onions should be welcomed by all who tear while chopping onions and those who work in facilities where fresh onions are processed.
The lachrymatory factor in onions was isolated by gas chromatography of a raw onion extract. By means of spectral analysis, the isolate was identified as thiopropanal S-oxide. Synthesis confirmed this identification. Thioethanal, thioacetone, thiobutanal, and thiohexanal S-oxides were also synthesized and their lachrymogenic properties were evaluated.
Allicin (diallylthiosulfinate) is the main biologically active component of freshly crushed garlic cloves. It is produced upon the interaction of the nonprotein amino acid alliin with the enzyme alliinase (alliin lyase, EC 4.4.1.4). A simple and rapid spectrophotometric procedure for determination of allicin and alliinase activity, based on the reaction between 2-nitro-5-thiobenzoate (NTB) and allicin, is described. NTB reacts with the activated disulfide bond --S(O)-S--; of allicin, forming the mixed-disulfide allylmercapto-NTB, as characterized by NMR. The method can be used for determination of allicin and total thiosulfinates in garlic preparations and garlic-derived products. The method was applied for determination of pure alliinase activity and for the activity of the enzyme in crude garlic extracts.
Allicin (diallylthiosulfinate) is the best known active compound of garlic. It is generated upon the interaction of the nonprotein amino acid alliin with the enzyme alliinase (alliin lyase, EC 4.4.1.4). Previously, we described a simple spectrophotometric assay for the determination of allicin and alliinase activity, based on the reaction between 2-nitro-5-thiobenzoate (NTB) and allicin. This reagent is not commercially available and must be synthesized. In this paper we describe the quantitative analysis of alliin and allicin, as well as of alliinase activity with 4-mercaptopyridine (4-MP), a commercially available chromogenic thiol. The assay is based on the reaction of 4-MP (lambda(max)=324nm) with the activated disulfide bond of thiosulfinates -S(O)-S-, forming the mixed disulfide, 4-allylmercaptothiopyridine, which has no absorbance at this region. The structure of 4-allylmercaptothiopyridine was confirmed by mass spectrometry. The method was used for the determination of alliin and allicin concentrations in their pure form as well as of alliin and total thiosulfinates concentrations in crude garlic preparations and garlic-derived products, at micromolar concentrations. The 4-MP assay is an easy, sensitive, fast, noncostly, and highly efficient throughput assay of allicin, alliin, and alliinase in garlic preparations.
The irritating lachrymatory factor that is released by onions when they are chopped up has been presumed to be produced spontaneously following the action of the enzyme alliinase, which operates in the biochemical pathway that produces the compounds responsible for the onion's characteristic flavour. Here we show that this factor is not formed as a by-product of this reaction, but that it is specifically synthesized by a previously undiscovered enzyme, lachrymatory-factor synthase. It may be possible to develop a non-lachrymatory onion that still retains its characteristic flavour and high nutritional value by downregulating the activity of this synthase enzyme.
The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF. To shed light on the mechanism of LF production in the onion, we solved crystal structures of LFS in an apo-form and in complex with a substrate analogue, crotyl alcohol. The enzyme closely resembles the helix-grip fold characteristic for plant representatives of START (star-related lipid transfer) domain-containing protein superfamily. By comparing the structures of LFS to that of the abscisic acid receptor, PYL10, a representative of the START protein superfamily, we elucidated structural adaptations underlying the catalytic activity of LFS. We also delineated the architecture of the active site, and based on the orientation of the ligand, we propose a mechanism of catalysis that involves sequential proton transfer accompanied by formation of a carbanion intermediate. These findings reconcile chemical and biochemical information regarding thioaldehyde S-oxide formation and close a long-lasting gap in understanding of the mechanism responsible for LF production in the onion.
Several novel sulfides from acetone extracts of bulbs of garlic (Allium sativum L.), were identified and investigated. These were named garlicnins B1 (1), C1 (2), and D (3), and they were found to have the ability to control macrophage activation. Garlicnins B1 (1) and C1 (2) possess a new skeleton of cyclic sulfoxide and their structures of garlicnins B1 (1) and C1 (2) were characterized as 3,4-dimethyltetrahydrothiophene-S-oxide derivatives carrying the substitutions of a propenyl and a sulfenic acid, and an allyldithiine and a 1-propene-sulfenic acid (a), respectively. The mechanism of the proposed production of these compounds is discussed. Garlicnin D (3), dithiine-type, was estimated to be derived by addition of (a)+allyl thiosulfenic acid (b) derived from allicin. The identification of these novel sufoxides from onion and garlic accumulates a great deal of new chemistry to the Allium sulfide field, and future pharmacological investigations aid the development of natural, healthy foods and anti-cancer agents that could potentially prevent or combat disease.
In this study, the new stable sulfur-containing compounds onionins A2 (1) and A3 (2) were isolated from the acetone extracts of the bulbs of Allium cepa L. and identified as the stereoisomers of onionin A1 discovered in our previous study. Their chemical structures, 3,4-dimethyl-5-(1E-propenyl)-tetrahydrothiophene-2-sulfenic acid-S-oxides, were characterized using various spectroscopic techniques. In addition, 1 and 2 together with onionin A1 were successfully isolated from the leaves of the Welsh onion, Allium fistulosum L. The onion-extracted fractions showed good potential to inhibit the polarization of M2 activated macrophages, indicating their possible ability to inhibit tumor cell proliferation.
Five new sulphur-containing compounds and five diastereoisomers which indicated potent inhibitory efrects for collagen-induced aggregation of human platelets in vitro as well as ADP- or arachidonate-induced aggregation were isolated from onion. All isolated compounds have a 1-(methylsulphinyl)-propyl alkyl (or alkenyl) disulphide skeleton. It was predicted that they were formed by the interaction of the onion lachrymatory factor, thiopropanal S-oxide, with alkane (or alkene) sulphenic acids produced in crushed onion.
Reduction (LiAlH4) of propyl 1-propynyl sulfide (8) to (E)-1-propenyl propyl sulfide ((E)-10), C−S cleavage (Li/NH3) to lithium (E)-1-propenethiolate (Li (E)-11), and reaction with MeSO2Cl gives (E,E)-bis(1-propenyl) disulfide ((E,E)-2); i-Bu2AlH reduction of 8 to (Z)-10 and reaction with Li/NH3 and then MeSO2Cl gives (Z,Z)-2 via Li (Z)-11. Reaction of MeSO2SR (R = Me (12a), n-Pr (12b), CH2CHCH2 (12c), CHCHMe (12d)) with K (E)-11 gives (E,Z)-2 from (Z)-12d; Li (E,Z)-11 gives alkyl (E)- and (Z)-1-propenyl disulfides (MeCHCHSSR, R = Me (3a), n-Pr (3b), CH2CHCH2 (3c)) from 12a−c, respectively. Oxidation at −60 °C of (E,E)-, (Z,Z)-, and (E,Z)-2 gives (E)-1-propenesulfinothioic acid S-(E)-1-propenyl ester ((E,E)-13, (E,E)-MeCHCHS(O)SCHCHMe) from (E,E)-2, (Z,Z)-13 from (Z,Z)-2, and ca. 2:1 (E,Z)-13)/(Z,E)-13 from (E,Z)-2. Warming (Z,Z)-13 gives (±)-(1α,2α,3β,4α,5β)-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxide (1a), endo-5-methyl-exo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane (14a), and exo-5-methyl-endo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane (14b). Warming (E,E)-13 gives 14a and 14b; (E,Z)-13/(Z,E)-13 gives (1α,2α,3α,4α,5β)-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxide (1b), exo-5-methyl-exo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane (14c), and endo-5-methyl-endo-6-methyl-2-oxa-3,7-dithiabicyclo[2.2.1]heptane (14d). Oxidation of 3a−c gives MeCHCHSS(O)R (4) and MeCHCHS(O)SR (5). At −60 °C, m-CPBA (2 equiv) converts (E,E)-2 into (Z,Z)-d,l-2,3-dimethyl-1,4-butanedithial 1,4-dioxide (26) while (Z,Z)-2 gives meso- and d,l-26. With NaIO4, 4/5 (R = Me) gives (E)- or (Z)-12a and MeCHCHSO2SMe (6a); with m-CPBA (Z)-MeS(O)CHMeCHS+O- (25a) forms. At 85 °C 2 gives 1:1 cis- and trans-2-mercapto-3,4-dimethyl-2,3-dihydrothiophene (29).
Thermal treatment of aqueous solutions of xylose and primary amino acids led to rapid development of a bitter taste of the reaction mixture. To characterize the key compound causing this bitter taste, a novel bioassay, which is based on the determination of the taste threshold of reaction products in serial dilutions of HPLC fractions, was developed to select the most intense taste compounds in the complex mixture of Maillard reaction products. By application of this so-called taste dilution analysis (TDA) 21 fractions were obtained, among which 1 fraction was evaluated with by far the highest taste impact. Carefully planned LC-MS as well as 1D and 2D NMR experiments were, therefore, focused on the compound contributing the most to the intense bitter taste of the Maillard mixture and led to its unequivocal identification as the previously unknown 3-(2-furyl)-8-[(2-furyl)methyl]4-hydroxymethyl-1-oxo-1H,4H-quinolizinium-7-olate. This novel compound, which we name quinizolate, exhibited an intense bitter taste at an extraordinarily low detection threshold of 0.00025 mmol/kg of water. As this novel taste compound was found to have 2000- and 28-fold lower threshold concentrations than the standard bitter compounds caffeine and quinine hydrochloride, respectively, quinizolate might be one;of the most intense bitter compounds reported so far.
A Cook's tour is presented of the organosulfur chemistry of the genus Allium, as represented, inter alia, by garlic (Allium sativum L.) and onion (Allium cepa L.). We report on the biosynthesis of the S-alk(en)yl-L-cysteine S-oxides (aroma and flavor precursors) in intact plants and on how upon cutting or crushing the plants these precursors are cleaved by allinase enzymes, giving sulfenic acids—highly reactive organosulfur intermediates. In garlic, 2-propenesulfenic acid gives allicin, a thiosulfinate with antibiotic properties, while in onion 1-propenesulfenic acid rearranges to the sulfine (Z)-propanethial S-oxide, the lachrymatory factor (LF) of onion. Highlights of onion chemistry include the assignment of stereochemistry to the LF and determination of the mechanism of its dimerization; the isolation, characterization, and synthesis of thiosulfinates which most closely duplicate the taste and aroma of the freshly cut bulb, and additional unusual compounds such as zwiebelanes (dithiabicyclo[2.1.1]hexanes), a bis-sulfine (a 1,4-butanedithial S,S′-dioxide), antithrombotic and antiasthmatic cepaenes (α-sulfinyl disulfides), and vic-disulfoxides. Especially noteworthy in the chemistry of garlic are the discovery of ajoene, a potent antithrombotic agent from garlic, and the elucidation of the unique sequence of reactions that occur when diallyl disulfide, which is present in steam-distilled garlic oil, is heated. Reaction mechanisms under discussion include [3, 3]- and [2, 3]-sigma-tropic rearrangements involving sulfur (e.g. sulfoxide-accelerated thio- and dithio-Claisen rearrangements) and cycloadditions involving thiocarbonyl systems. In view of the culinary importance of alliaceous plants as well as the unique history of their use in folk medicine, this survey concludes with a discussion of the physiological activity of the components of these plants: cancer prevention, antimicrobial activity, insect and animal attractive/repulsive activity, olfactory–gustatory–lachrymatory properties, effect on lipid metabolism, platelet aggregation inhibitory activity and properties associated with ajoene. And naturally, comments about onion and garlic induced bad breath and heartburn may not be overlooked.
Fast MS techniques have been applied to the analysis of sulfur volatiles in Allium species and varieties to distinguish phenotypes. Headspace sampling by proton transfer reaction (PTR) MS and surface sampling by desorption electrospray ionization (DESI) MS were used to distinguish lachrymatory factor synthase (LFS)-silenced (tearless; LFS-) onions from normal, LFS active (tear-inducing; LFS+), onions. PTR-MS showed lower concentrations of the lachrymatory factor (LF, 3) and dipropyl disulfide 12 from tearless onions. DESI-MS of the tearless onions confirmed the decreased LF 3, and revealed much higher concentrations of the sulfenic acid condensates. Using DESI-MS with MS2 could distinguish zwiebelane ions from thiosulfinate ions. DESI-MS gave reliable fast phenotyping of LFS+ versus LFS- onions by simply scratching leaves and recording the extractable ions for <0.5 min. DESI-MS leaf compound profiles also allowed the rapid distinction of a variety of Allium cultivars to aid plant breeding selections.
A series of 1-[alk(en)ylsulfinyl]propyl alk(en)yl disulfides (α-sulfinyl disulfides) of structure RS(O)CHEtSSR‘, R, R‘ = Me, (E,Z)-MeCHCH, n-Pr, and CH2CHCH2, termed cepaenes, have been synthesized by a variety of routes including oxidation of 1-[alk(en)ylthio]propyl alk(en)yl disulfides, RSCHEtSSR‘, termed deoxycepaenes. The cepaenes are identical to compounds isolated from homogenates of onion (Allium cepa) and to compounds identified in these homogenates by liquid chromatography/mass spectrometry, while the deoxycepaenes are identical to compounds found in Allium distilled oils and in other materials. The antithrombotic activities for several cepaenes are reported. Keywords: Allium chemistry; onion (Allium cepa); a-sulfinyl disulfides; cepaenes; antithrombotic compounds
Trans-(+)-S-1-Propenyl-l-cysteine S-oxide, hitherto reported to be enzymatically transformed into the lachrymatory substance of freshly comminuted onion tissue, has now also been found to be the sole precursor of the substance responsible for the bitter taste in onion macerates. From a consideration of its concentration in onion, its properties as a substrate for enzyme action, and the relatively strong sensory responses elicited from such enzyme action, it is concluded this propenyl derivative is to a large degree responsible for the development of all of the sensory attributes perceived upon comminution of onion tissue.
The lachrymatory factor of the onion is shown by NMR analysis to be a 19 to 1 mixture of (Z)- and (E)-propanethial S-oxide.
Several novel sulfides from acetone extracts of bulbs of garlic (Allium sativum L.), were identified and investigated. These were named garlicnins B(1) (1), C(1) (2), and D (3), and they were found to have the ability to control macrophage activation. Garlicnins B(1) (1) and C(1) (2) possess a new skeleton of cyclic sulfoxide and their structures of garlicnins B(1) (1) and C(1) (2) were characterized as 3,4-dimethyltetrahydrothiophene-S-oxide derivatives carrying the substitutions of a propenyl and a sulfenic acid, and an allyldithiine and a 1-propene-sulfenic acid (a), respectively. The mechanism of the proposed production of these compounds is discussed. Garlicnin D (3), dithiine-type, was estimated to be derived by addition of (a)+allyl thiosulfenic acid (b) derived from allicin. The identification of these novel sufoxides from onion and garlic accumulates a great deal of new chemistry to the Allium sulfide field, and future pharmacological investigations aid the development of natural, healthy foods and anti-cancer agents that could potentially prevent or combat disease.
From the chloroform extract of onion juice five partially new thiosulphinates and six hitherto unknown α-sulphinyldisulphides (‘cepaenes‘) were isolated and their structures elucidated as trans-and cis-methylsulphinothioic acid-S- 1-propenyl ester, cis- and trans- n-propylsulphinothioic acid-S-1-propenyl ester, n-propylsulphinothioic acid-S-n-propyl ester and trans-5-ethyl-4,6,7-trithia-2-decene 4-S-oxide, trans, trans and trans, cis 5-ethyl-4,6,7-trithia-2,8-decadiene 4-S-oxide and the diastereoisomers of the latter three compounds. Structure elucidation was performed mainly by CI/EIMS and highfield NMR spectroscopy. The α-β-unsaturated thiosulphinates exert antiasthmatic activity in vivo and both thiosulphinates and α-sulphinyldisulphides were found to be dual inhibitors of cyclooxygenase and 5-lipoxygenase in vitro.
In normal onion (Allium cepa), trans-S-1-propenyl-L-cysteine sulfoxide is transformed via 1-propenesulfenic acid into propanethial S-oxide, a lachrymatory factor, through successive reactions catalyzed by alliinase and lachrymatory factor synthase (LFS). A recent report showed that suppression of the LFS activity caused a dramatic increase in thiosulfinates previously reported as "zwiebelane isomers". After purification by recycle high-performance liquid chromatography and subsequent analyses, we established the planar structure of the putative "zwiebelane isomers" as S-3,4-dimethyl-5-hydroxythiolane-2-yl 1-propenethiosulfinate, in which two of the three molecules of 1-propenesulfenic acid involved in the formation gave the thiolane backbone, and the third molecule gave the thiosulfinate structure. Of at least three stereoisomers observed, one in the (2'R,3'R,4'R,5'R)-configuration was collected as an isolated fraction, and the other isomers were collected as a combined fraction because spontaneous tautomerization prevented further purification. Both fractions showed inhibitory activities against cyclooxygenase-1 and α-glucosidase in vitro.
Onionin A (1), a new, stable, sulfur-containing compound, was isolated from acetone extracts of bulbs of onion (Allium cepa), and its structure was characterized as 3,4-dimethyl-5-(1E-propenyl)-tetrahydrothiophen-2-sulfoxide-S- oxide, on the basis of the results of spectroscopic analysis. This compound showed the potential to suppress tumor-cell proliferation by inhibiting the polarization of M2 alternatively activated macrophages. © 2010 The American Chemical Society and American Society of Pharmacognosy.
A novel HPLC method for determination of a wide variety of S-substituted cysteine derivatives in Allium species has been developed and validated. This method allows simultaneous separation and quantification of S-alk(en)ylcysteine S-oxides, gamma-glutamyl-S-alk(en)ylcysteines and gamma-glutamyl-S-alk(en)ylcysteine S-oxides in a single run. The procedure is based on extraction of these amino acids and dipeptides by methanol, their derivatization by dansyl chloride and subsequent separation by reversed phase HPLC. The main advantages of the new method are simplicity, excellent stability of derivatives, high sensitivity, specificity and the ability to simultaneously analyze the whole range of S-substituted cysteine derivatives. This method was critically compared with other chromatographic procedures used for quantification of S-substituted cysteine derivatives, namely with two other HPLC methods (derivatization by o-phthaldialdehyde/tert-butylthiol and fluorenylmethyl chloroformate), and with determination by gas chromatography or capillary electrophoresis. Major advantages and drawbacks of these analytical procedures are discussed. Employing these various chromatographic methods, the content and relative proportions of individual S-substituted cysteine derivatives were determined in four most frequently consumed alliaceous vegetables (garlic, onion, shallot, and leek).
Thermal treatment of aqueous solutions of xylose and primary amino acids led to rapid development of a bitter taste of the reaction mixture. To characterize the key compound causing this bitter taste, a novel bioassay, which is based on the determination of the taste threshold of reaction products in serial dilutions of HPLC fractions, was developed to select the most intense taste compounds in the complex mixture of Maillard reaction products. By application of this so-called taste dilution analysis (TDA) 21 fractions were obtained, among which 1 fraction was evaluated with by far the highest taste impact. Carefully planned LC-MS as well as 1D and 2D NMR experiments were, therefore, focused on the compound contributing the most to the intense bitter taste of the Maillard mixture and led to its unequivocal identification as the previously unknown 3-(2-furyl)-8-[(2-furyl)methyl]-4-hydroxymethyl-1-oxo-1H,4H-quinolizinium-7-olate. This novel compound, which we name quinizolate, exhibited an intense bitter taste at an extraordinarily low detection threshold of 0.00025 mmol/kg of water. As this novel taste compound was found to have 2000- and 28-fold lower threshold concentrations than the standard bitter compounds caffeine and quinine hydrochloride, respectively, quinizolate might be one of the most intense bitter compounds reported so far.
A model reaction system was developed for generating pure thiosulfinates and propanethial-S-oxide (PTSO) using an isolated alliinase (EC 4.4.1.4) and isolated or synthetic alk(en)yl-L-cysteine sulfoxides (ACSO). Reaction yields ranged from 30 to 60% after 3 h at 21-23 degrees C, and organosulfur reaction products were extracted into CHCl3 to yield product preparations of controlled composition. A pure thiosulfinate or PTSO was derived from a single ACSO, and a preparation containing a mixture of four thiosulfinate species was derived from reaction mixtures employing binary ACSO substrate systems. Identities of homologous thiosulfinates and PTSO were confirmed by 1H NMR. This approach has the potential to be used as a preparative tool for yielding pure thiosulfinates and PTSO to facilitate the study of chemical and biological properties of this group of compounds or as a means to study the dynamics of organosulfur chemistry in preparations from Allium spp.
Identification and isolation of (R(S)R(C))-S-(methylthiomethyl)cysteine-4-oxide from rhizomes of Tulbaghia violacea Harv. is reported. The structure and absolute configuration of the amino acid have been determined by NMR, MALDI-HRMS, IR, and CD spectroscopy. Its content varied in different parts of the plant (rhizomes, leaves, and stems) between 0.12 and 0.24 mg g(-1) fr. wt, being almost equal in the stems and rhizomes. In addition, S-methyl- and S-ethylcysteine derivatives have been detected in minute amounts (<3 microg g(-1) fr. wt) in all parts of the plant. The enzymatic cleavage of the amino acid and subsequent odor formation are discussed. 2,4,5,7-Tetrathiaoctane-4-oxide, the primary breakdown product, has been detected and isolated for the first time.
Isolation and identification of (S(S)R(C))-S-n-butylcysteine sulfoxide (1) from the bulbs of Allium siculum is reported. This compound was found in all parts of the plant (bulbs, stem, leaves, and flowers) along with known compounds (S(S)R(C))-S-methyl- and (R(S)R(C))-(E)-S-(1-propenyl)cysteine sulfoxides (2 and 3, respectively). In addition, six n-butyl-containing thiosulfinates (4-9) have been found in a CH2Cl2 extract of the bulbs. Structures were determined by a combination of spectral methods (primarily NMR and MS) and by comparison with authentic compounds obtained by synthesis. Antimicrobial activities of 4-7 and 9 are reported.
Precursors involved in the formation of pink and green-blue pigments generated during onion and garlic processing, respectively, have been studied. It has been confirmed that the formations of both pigments are of very similar natures, with (E)-S-(1-propenyl)cysteine sulfoxide (isoalliin) serving as the primary precursor. Upon disruption of the tissue, isoalliin and other S-alk(en)ylcysteine sulfoxides are enzymatically cleaved, yielding 1-propenyl-containing thiosulfinates [CH3CH=CHS(O)SR; R = methyl, allyl, propyl, 1-propenyl] among others. The latter compounds have been shown to subsequently react with amino acids to produce the pigments. Whereas the propyl, 1-propenyl, and methyl derivatives form pink, pink-red, and magenta compounds, those containing the allyl group give rise to blue products after reacting with glycine at pH 5.0. The role of other thiosulfinates [RS(O)SR'] (R, R' = methyl, allyl, propyl) and (Z)-thiopropanal S-oxide (the onion lachrymatory principle) in the formation of the pigments is also discussed.
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