Thiosulfinates sulfenic acids

The thermolysis of acyclic- and/or six- and larger ring sulfoxides to yield olefins and sulfenic acids is well documented . The formation of allylic sulfenic acids and thiosulfinates in the thermolysis of thiirane oxides containing hydrogen on the a-carbon of the ring substituent (which is syn to the S—O bond) has been discussed previously in terms of /i-elimination of hydrogen, which is facilitated by relief of strain in the three-membered ring (Section llI.C.l). 

Much attention has been devoted to the acid- and nucleophile-catalyzed racemization of thiosulfinates. As a result of the extensive studies by Kice and his co-workers (112) and by Fava (281), it is clear now that the easy racemization of thiosulfinates caused by acids and bases (e.g., pyridine) is related to the scission of the sulfur-sulfur bond and the formation of sulfenic acid or its anion as an achiral intermediate. As expected, introduction of steric hindrance... 

Another simple elimination reaction on the thiosulfinate ester makes another molecule of the sulfenic acid and a highly unstable unsaturated thioaldehyde, which promptly dimerizes to give a thioacetal found in garlic as a potent platelet aggregation inhibitor. 

In onions, things start much the same way but the initial amino acid is not quite the same. The skeleton is the same as that of the garlic compound but the double bond is conjugated with the sulfoxide. Elimination and dimerization of the sulfenic acid produce an isomeric thiosulfinate. 

Oxidation of the thiosulfinate ester up to the sulfonate level gives the compound responsible for the lell of raw onions, while a hydrogen shift on the conjugated sulfenic acid (not possible with the garlic impound) gives a sulfine, the sulfur analogue of a ketene. The compound has the Z configuration cted from the mechanism and is the lachrymator that makes you cry when you cut into a raw onion. 

When garlic is mechanically disrupted, alliinase or alliin lyase (EC 4.4.1.4.) catalyzes the conversion of the cysteine sulfoxides to the biologically active diallyl thiosulfinates via sulfenic acid intermediates (Block, 1992). Alliinase is localized to a few vascular bundle sheath cells around the veins or phloem, whereas alliin and other cysteine sulfoxides are found in the clove mesophyll storage cells. This enzyme is approximately 10 times more abundant in the cloves than in the leaves and accounts for at least 10% of the total protein in the cloves (Ellmore and Feldberg, 1994). Alliinase is temperature and pH dependent optimal activity is between pH 5.0-10.0, but allinase can be irreversibly deactivated at pH 1.5-3.0 (Krest and Keusgen, 1999). 

The reduction of the disulfide dication (36) to the disulfide can be achieved upon treatment with two equivalents of KI or Bu 4N I . However, treatment with KBr followed by aqueous workup gives acyclic dimers. The reaction mechanism outlined in Scheme 14 shows the formation of sulfenyl bromide (46) which is hydrolyzed into the sulfenic acid (47) which in turn dimerizes into the thiosulfinate intermediate. 

We have used chiral y-cyclodextrin GC columns under isothermal GC-MS conditions (column temperature 9 120 ) and found that enantiomers of /ran -zwiebelane (9a, Figure 2) and the thiosulfinates MeS(0)SMe, MeS(0)SPr-/i, and MeSS(0)Pr-/i (Figure 3) can be resolved and that individual enantiomers are stable under the analytical conditions (25). However, analysis of an onion extract on the chiral column showed that all of these con unds were present as racemic mixtures, su esting that asymmetric induction is not involved in their formation from achiral sulfenic acid ... 

The flavor precursors, 5 -alk(en)yl-L-cysteine sulfoxides, themselves do not have any specific flavor. However, when garlic or onion cells are damaged by cutting or crushing and the 5 -alk(en)yl-L-cysteine sulfoxides meet the C-S lyase (alliinase), they are converted into various volatile sulfuric compounds. Stoll and Seebeck (1951) first proposed the production of diallyl thiosulfinate (allicin) from the 5 -allyl-L-cysteine sulfoxide (alliin) by the C-S lyase. Through the reaction catalyzed by the C-S lyase, 5 -alk(en)yl-L-cysteine sulfoxides yield alk(en)yl sulfenic acid and aminoacrylic acid, the latter being spontaneously degraded... 

Similar to the S-allyl-L-cysteine sulfoxide in garlic, the C-S lyase can also catalyze the flavor formation from the 5 -methyl-L-cysteine sulfoxide. Therefore, when garlic is cut or crushed, methyl sulfenic acid and allyl sulfenic acid can be produced from 5 -methyl-L-cysteine sulfoxide and S-allyl-L-cysteine sulfoxide, respectively (Figure 18.5). As sulfenic acids are quite reactive, methyl sulfenic acid and allyl sulfenic acid will quickly form the metiiyl 2-propenethiosulfinate and allyl methaneth-iosulfinate. With the similar reaction to that from diallyl thiosulfinate, these thiosulfinates produce allyl methyl disulfide and allyl methyl trisulfide. 

When onion is cut or cmshed, ( )-5 -l-propenyl-L-cysteine sulfoxide (isoalliin) is converted into ( )-l-propene-l-sulfenic acid. Different from garlic, (Z)-thiopropanal S-oxide, a lachrymatory factor, is formed from the sulfenic acid by lachrymatory factor synthase (Figure 18.6). The remaining ( )-l-propene-l-sulfenic acid and methyl sulfenic acid produced from 5 -methyl-L-eysteine sulfoxide ean form methyl 1-pro-pene-thiosulfinate and 1-propenyl methane thiosulfinate that are further converted to sulfides such as 1-propenyl methyl disulfide and 1-prope-nyl methyl trisulfide. 

Even considering the difference in the amount of 5 -alk(en)yl-L-cysteine sulfoxide, the total amount of thiosulfinates produced from onion is significantly lower than that from garlic being approximately 0.01-0.035 mg/g-fresh weight (Table 18.2). The reason for this is because most of the ( )-l-propene-l-sulfenic acid produced from E)-S-1-propenyl-L-cysteine sulfoxide is converted into a lachrymatory factor, and not so much can be used for the production of thiosulfinates. 

The mechanism of flavor formation from the alkyl cysteine sulfoxide (alhin) is outlined in Figure 4.13. While the initial steps of this pathway are enzymatic, reactions beyond sulfenic acid are purely chemical in nature. Sulfenic acid is extremely reactive, readily forming the unstable thiosulfinate intermediate by reaction with a second sulfenic acid molecule. This thiosulfinate decomposes to form a relatively stable thiosulfonate and mono, di- and trisulfldes. Considering that several different aUcyl precursors are available in each Allium species, a host of different mono-, di-, and trisulfides can be formed via different sulfenic acid combinations. It is these mono-, di-, and trisulfides that are most important in determining typical Allium flavor. 

On standing, the sulfenic acid (34) dimerized to the thiosulfinate (35) (Chou et al., 1976), which then rearranged on brief heating via a cyclic elimination process to the thione (36). 

An alternate synthesis of the thione isomer (37) resulted from the reaction of the sulfenic acid (31) with ct-propylmercaptan from which the disulfide (38) was isolated. This was then converted to the thiosulfinate (39) with w-chloroperbenzoic acid. Thermal treatment of 39 gave the thione (37). 

Buffer catalysis of the hydrolysis of phenyl (311 R = Ph) and methyl (311 R = Me) benzenesulfinates to give the sulfinic acid (312) and alcohol ROH is strongly accelerated by both carboxylate and amine components of the buffer which give Bronsted /i values of approximately unity on separate lines. The carboxylates are about 44 tunes more effective than amines of similar basicity. A concerted. S n2 mechanism with a hypervalent intermediate (313) is proposed for the nucleophilic reaction of these esters.286 The reaction of the thiosulfinate esters (314) with sulfenyl chlorides RSCI and sulfenate esters (315) to give sulfinyl chlorides and disulfides and sulfinate esters and disulfides, respectively, has been studied.287 Hydrolysis of 2-(3-aminophenyl)sulfonyl-ethanol hydrogensulfate gives under different conditions various products such as the ether (316) and the sulfone (317).288... 

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