Diallyl disulfide

Diallyl disulfide
IUPAC name

4,5-dithia-1,7-octadiene
Diallyldisulfide
Other names

Garlicin, DADS
Identifiers
CAS number 2179-57-9 Y
PubChem 16590
ChemSpider 15730 Y
KEGG C08369 Y
ChEBI CHEBI:4488 Y
ChEMBL CHEMBL366603 Y
Jmol-3D images Image 1
Properties
Molecular formula C6H10S2
Molar mass 146.28 g/mol
Appearance yellowish clear liquid with an intense garlic smell[1]
Density 1.01 g/cm3[2]
Boiling point

180 °C
Solubility in water soluble in ethanol and oils[1]
Hazards
R-phrases 22-36/37/38
S-phrases 22-36/37/38
 Y (verify) (what is: Y/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Diallyl disulfide (DADS or 4,5-dithia-1,7-octadiene) is an organosulfur compound found in plants of the genus Allium. Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the distilled oil of garlic. It is a yellowish liquid which is insoluble in water and has a strong garlic odor. It is produced during the decomposition of allicin, which is released during incision of garlic and other plants of the Alliaceae family. Diallyl disulfide has many health benefits of garlic, but it also an allergen causing the garlic allergy. Highly diluted, it is used as a flavoring in the food.

Contents

History

In 1844, Theodor Wertheim separated by steam distillation a pungent-smelling substance from garlic and named it "allyl", however only in 1892 Friedrich Wilhelm Semmler could identify diallyl disulfide as one of the components of the product. Its precursor, allicin, was discovered in 1944 by Chester J. Cavallito and John Hays Bailey. In 1947, A. Stoll and E. Seebeck found that DADS and allicin can be produced from derivatives of cysteine (such as alliin) using the enzyme alliinase.[3]

Occurrence

Diallyl disulfide is produced by decomposition of allicin, which is released upon breaking the cells of the Alliaceae plants, especially garlic, onion and leek. The DADS yield is the highest for the steam distillation of garlic bulbs which contain about 2 wt.% of DADS-rich oil. DADS can also be extracted from garlic leaves, but their oil content is significantly lower at 0.06 wt.%.[4][5]

Extraction and representation

On industrial scale, diallyl disulfide is produced from sodium disulfide and allyl bromide or allyl chloride at temperatures of 40–60 °C in an inert gas atmosphere; sodium disulfide is generated in situ by reacting sodium sulfide with sulfur. The reaction is exothermic and its theoretical efficiency of 88% has been achieved in practice.[6]


Smaller quantities can be synthesized from the same starting materials, but in air and using tetrabutylammonium as a catalyst. The corresponding yield is below 82%.[7] The major problem, both in the industrial synthesis and in the extraction from plants, is separation of diallyl disulfide from higher sulfides (diallyl trisulfide (DATS), etc.). They have very similar physical properties and therefore, a typical commercial product contains only 80% of diallyl disulfide. The reduction of allicin to diallyl disulfide takes place particularly rapidly above 37 °C.[8]

Properties

Physical characteristics

DADS has a strong garlic smell. It is a clear, yellowish liquid which boils at 138–139 °C (for the typical 80% purity) and has its flash point at 50 °C, a density of about 1.0 g/mL and a vapor pressure of 1 mmHg at 20 °C. It is non-polar; therefore, DADS is insoluble in water and is soluble in fats, oils, lipids, and non-polar solvents such as hexane or toluene.[1][2]

Chemical reactions

Diallyl disulfide can oxidize to allicin, which can dissociate back to the diallyl disulfide (top right in the figure). In presence of a catalyst, it can combine with alkyl halide forming 1-alkylthio-3-1-propene and 1,3-di(alkylthio)propene (left).[9] With a ruthenium-based catalyst, DADS can produce sulfur-containing hetero-polycycles.[10]

Applications

In presence of iron chloride or copper chloride catalyst, DADS can be used as a precursor for the synthesis of higher diallyl polysulfides. It is also a starting material for the synthesis of allicin. In food industry, DADS is used to improve the taste of meat, vegetables and fruits.[1][11]

Biological importance

Smell and taste

The unpleasant smell of DADS is perceived through the transient receptor potential cation channel, member A1 (TRPA1). This ion channel had long been present not only in humans and animals, but even in fungi. Thus, Alliaceae plants have likely developed the DADS-TRPA1 protection mechanism against predators at the early stages of the evolution.[12][13]

Poisoning and detoxification

Diallyl disulfide is an efficient agent for detoxication of the cells. It significantly increases the production of the enzyme glutathione S-transferase (GST), which binds electrophilic toxins in the cell. Garlic therefore supports, for example, the detoxification function of liver cells in vitro and protects nerve cells from oxidative stress, also in vitro.[14][15][16][17][18][19][20][21] The detoxification effect may prevent symptoms of inflammation. This was confirmed a study on rats where prolonged administration of DADS protected poisoning of their intestinal cells. This study also showed that certain side effects of high doses of garlic oil are not attributable to the diallyl disulfide.[22] By supporting the detoxification activity in the liver, diallyl disulfide might offer liver protection during the chemotherapy, e.g. against cyanide detoxification.[23][24]

Antimicrobial effect

The release of organosulfur compounds upon destruction of Alliaceae plant cells has great importance, because of the antimicrobial, insecticidal and larvicidal properties of those compounds.[25] In particular, DADS is the main reason for inhibiting the growth of molds and bacteria by garlic oil. It is also acts against the stomach ulcer germ Helicobacter pylori, however not as efficiently as allicin.[26][27] Because of its antimicrobial effects, diallyl disulfide, together with tobramycin, is included to preparations which are used for selective decontamination of the organs (e.g. gut) before surgical operations. A clinical study showed that such preparations prevent endotoxemia in heart valve operations.[28]

Protection against colon cancer

Garlic can prevent the colorectal cancer,[29] and several studies revealed that diallyl disulfide is a major component responsible for this action. The effect is dose dependent as demonstrated on mice.[30][31] DADS affects cancer cells much stronger than normal cells.[32] It also results in a strong and dose-dependent accumulation of several agents, such as reactive oxygen species, which activate enzyme and lead to destruction of cancer cells.[33]

Protection against cardiovascular disease

There is evidence that garlic may prevent the development of cardiovascular diseases. A possible reason for some of these diseases, such as atherosclerosis or coronary heart disease is oxidative stress. The latter is reduced by diallyl disulfide by assisting in the detoxification of the cell, as well as some other mechanisms.[3] By activating the TRPA1 ion channel, DADS leads to a short-term lowering of blood pressure.[12]

Safety

DADS is a skin irritant and an allergen. In particular, it is the main cause of garlic allergy (allergic contact dermatitis to garlic), which especially affects chefs and housewives. The allergy usually starts at the fingertips and can not be prevented by wearing gloves because DADS penetrates through most commercial glove types.[34][35][36][37]

The median lethal dose (LD50) for oral intake in rats is 260 mg per kg of body weight and it is 3.6 g/kg for dermal intake. High doses of 5 g/kg placed on the skin of cats cause death through hemolytic anemia.[1][38]

DADS can be easily detected in the air or in the blood with gas chromatography.[39][40]

See also

References

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  2. ^ a b Diallyl disulfide at Sigma Aldrich
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  6. ^ WIPO Patent WO/2006/16881
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  9. ^ Amosova SV et al. :Synthesis of 1-alkylthio-3-allylthio-1-propene by the reaction of allyl halides with dialllyl disulfide in the alkali-metal hydroxide-DMSO system super basic J. Org. Chem USSR (Engl Transl.) Vol. 22 No. 5, 1986, pp. 957–963. Abstract
  10. ^ Kondo T. et al.Cyclization Ruthenium Complex-Catalyzed Novel Addition Reaction of Allylic Disulfide with 2 -norbornene.Nippon Kagakkai Koen Yokoshu. 76/21999, p. 922 Abstract
  11. ^ U.S. Patent 5,231,114
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  36. ^ Garlic
  37. ^ Moyle, M; Frowen, K; Nixon, R (2004). "Use of gloves in protection from diallyl disulphide allergy". The Australasian journal of dermatology 45 (4): 223–5. doi:10.1111/j.1440-0960.2004.00102.x. PMID 15527433. 
  38. ^ EPA documents
  39. ^ documents of the U.S. Department of Labor Occupational Safety & Health
  40. ^ Sun, X; Guo, T; He, J; Zhao, M; Yan, M; Cui, F; Deng, Y (2006). "Simultaneous determination of diallyl trisulfide and diallyl disulfide in rat blood by gas chromatography with electron-capture detection". Die Pharmazie 61 (12): 985–8. PMID 17283653. 

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