α-Lipoic Acid

α-Lipoic Acid Property

Melting point:

60-62 °C

Boiling point:

160-165 °C(lit.)

Density 

1.2888 (rough estimate)

bulk density

260kg/m3

refractive index 

1.5200 (estimate)

Flash point:

160-165°C

storage temp. 

2-8°C

solubility 

ethanol: 50 mg/mL

pka

4.75±0.10(Predicted)

form 

Crystals or Crystalline Powder

color 

Yellow

biological source

synthetic

Water Solubility 

0.9 g/L (20 ºC)

Merck 

14,9326

BRN 

81853

Stability:

Stable. Incompatible with strong oxidizing agents.

Cosmetics Ingredients Functions

ANTIOXIDANT

InChI

1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10)

InChIKey

AGBQKNBQESQNJD-UHFFFAOYSA-N

SMILES

OC(=O)CCCCC1CCSS1

LogP

2.530 (est)

CAS DataBase Reference

1077-28-7(CAS DataBase Reference)

NIST Chemistry Reference

Dl-thioctic acid(1077-28-7)

Safety

Hazard Codes 

Xn

Risk Statements 

22-20/21/22

Safety Statements 

37/39-26-24/25-36-36/37/39

WGK Germany 

3

RTECS 

JP1192000

HS Code 

29349990

Storage Class

11 - Combustible Solids

Hazard Classifications

Acute Tox. 4 Oral
Aquatic Chronic 2
Eye Irrit. 2
Skin Irrit. 2
Skin Sens. 1

Hazardous Substances Data

1077-28-7(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H317May cause an allergic skin reaction

H319Causes serious eye irritation

H411Toxic to aquatic life with long lasting effects

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

α-Lipoic Acid Chemical Properties,Usage,Production

Description

DL-α-Lipoic acid is a cyclic disulfide antioxidant that interconverts with its reduced dithiol form. It is an essential cofactor for decarboxylation reactions of the citric acid cycle, and acts as a general antioxidant. DL-α-lipoic acid can act as a direct radical scavenger, as a cofactor to regenerate reduced glutathione, and as a metal chelator.

Chemical Properties

Light-Yellow Solid

Originator

Neurium,Hexal

Uses

Lipoic acid [CAS: 1077-28-7] (6,8-dimercaptooctanoic acid), a lipophilic endogenous disulfide that can be reduced to the dithiol dihydrolipoic acid, protects against free-radical-mediated injury both in vivo and in vitro.

Uses

A fat-metabolism stimulator

Uses

thioctic acid is also known as alpha lipoic acid. It is an anti-oxidant.

Uses

(±)-α-Lipoic acid has been used in in vitro lipoylation studies and in the pyruvate dehydrogenase complex (PDC)-pyruvate dehydrogenase kinase (PDHK) functional assay. It has also been used to investigate its antioxidative effect on developing cerebellum of rats exposed to arsenic during postnatal period.

Definition

ChEBI: Lipoic acid is a heterocyclic thia fatty acid comprising pentanoic acid with a 1,2-dithiolan-3-yl group at the 5-position. It has a role as a fundamental metabolite and a geroprotector. It is a member of dithiolanes, a heterocyclic fatty acid and a thia fatty acid. It is functionally related to an octanoic acid. It is a conjugate acid of a lipoate.

Manufacturing Process

To a suspension of 106 g of anhydrous aluminum chloride in 450 ml of carbontetrachloride is added dropwise, with vigorous stirring, 70 g of ethyl 8- chloroformylvalerate (H. Bergs, C. Wittfeld and H. Frank, Ber., 67B, 1622 (1947)). The temperature is maintained at 25°C. The cooling bath is removed and ethylene is passed in for a period of 2 hours. The reaction mixture is poured onto cracked ice, the organic layer separated, and the aqueous layer extracted with 200 ml of chloroform. The combined organic extracts are dried over anhydrous sodium sulfate and the solvent removed in vacuo. The dark colored oil remaining, crude ethyl 8-chloro-6-oxooctanoate is distilled in vacuo through a 6 in. Vigreaux column. After small forerun, the main fraction, 48-54 g (72-80%), B.P. 112-114°C (2 mm.); n25 D1-4485, is collected.
Redistilled thiolacetic acid (14.7 g) is cooled in an ice-bath and neutralized to the phenolphthalein end-point with a 10% solution of potassium hydroxide in ethanol (approximately 135 ml required). To this solution is added 29 g of ethyl-6,8-dibromooctanoate and the mixture is stirred and heated under reflux in an atmosphere of nitrogen for 5 hours. The reaction mixture, which contains ethyl 6,8-diacetyl-mercaptooctanoate, is cooled and 35 g of potassium hydroxide (85%) is added. The reaction mixture is stirred at room temperature in an atmosphere of nitrogen for 17 hours, then acidified (pH less than 1) with 6 N hydrochloric acid. Ethanol is removed in vacuo, sufficient water is added to dissolve the inorganic solids and the mixture is extracted with two 150 ml portions of chloroform. To the combined organic extracts, which contain 6,8-dimercaptooctanoic acid , is added 575 ml of chloroform and 210 ml of water. This mixture is stirred vigorously in an atmosphere of nitrogen While sufficient iodoform reagent (R. L. Shriner and R. C. Fuson, "Identification of Organic Compounds," 2nd. Ed., John Wiley and Sons, New York, N.Y., 1940, p. 53) is added dropwise during a 6 hour period to give a permanent brown color. Approximately 185 ml of iodoform reagent is required. The organic layer is separated, washed with 500 ml of 1% sodium thiosulfate solution, and then extracted with two 250 ml portions of 5% sodium bicarbonate solution. The aqueous extracts are acidified (pH less than 1) with 6 N hydrochloric acid and extarcted with two 125 ml portions of chloroform. The combined chloroform extracts are dried over anhydrous sodium sulfate and the solvent is then removed in vacuo. The yellow viscous oil remaining solidifies when cooled and scratched. This solid material is extracted with three 300 ml portions of boiling Skelly B solvent (essentially nhexane). The combined extracts are seeded with crystalline DL-α-lipoic acid and allowed to stand at room temperature overnight and then in a refrigerator for several hours. Large yellow crystals separate, M.P. 60.5-61.5°C. The yield of product is 10.8-12.3 g (60-68%). 1,2-Dithiolane-3-pentanoic acid was recrystallized from Skelly B solvent, M.P. 61-62°C.

brand name

Liposan;Thioactacid.

Therapeutic Function

Growth factor, Lipotropic, Detoxicant

Synthesis Reference(s)

Journal of the American Chemical Society, 79, p. 6483, 1957 DOI: 10.1021/ja01581a033

General Description

Oxidized form. Has antioxidant properties. Growth factor for many bacteria and protozoa.

Flammability and Explosibility

Not classified

Pharmaceutical Applications

Lipoic acid(ALA), also known as α-lipoic acid (alpha-lipoic acid) or thioctic acid, has the formula C₈H₁₄S₂O₂ and systematic name 5-(1,2-dithiolan-3-yl)pentanoic acid. It contains a disulfide group, which can be transformed in the body to a dithiol group.
ALA has been on the market since the 1950s as a dietary supplement. It is a natural antioxidant usually made by the body. The advantage of ALA over other antioxidants such as vitamin C and E is that it is soluble both in water and in fat. Researchers in the former Soviet Union found that ALA can chelate mercury once it is transformed into the dithiol-containing compound. ALA can penetrate both the blood–brain barrier and the cell membrane and therefore would be a very interesting chelating agent. Nevertheless, there is much debate about its mode of action, side effects and effectiveness. Other antidotes, such as BAL and DMSA, are more efficient in the removal of heavy metals. ALA has not received FDA approval as a chelating agent, but it is still sold as a food supplement.

Biological Activity

α-Lipoic Acid (ALA) is the only known antioxidant with both water and lipid solubility, known as the "universal antioxidant". This unique property enables ALA to enhance the body's antioxidant capacity through various mechanisms, including the direct scavenging of free radicals, regeneration of endogenous antioxidants, chelation of metal ions, and modulation of inflammatory responses.

Biochem/physiol Actions

Antioxidant and coenzyme needed for the activity of enzyme complexes such as those of pyruvate dehydrogenase and glycine decarboxylase. Exogenous thioctic acid is reduced intracellularly by two or more enzymes. The reduced form then influences a number of cell processes by direct radical scavenging, recycling of other antioxidants, increasing glutathione synthesis, and modulating transcription factor activity particularly that of NF-κB. Decreases the phagocytosis of myelin by macrophages.

Source

Animal products like red meat and organ meats are great sources of α-Lipoic Acid, but plant foods like broccoli, tomatoes, spinach, and Brussels sprouts also contain it.

storage

Store at +4°C

Purification Methods

It forms yellow needles from cyclohexane or hexane and has been distilled at high vacuum; and sublimes at ~90o and very high vacuum. It is insoluble in H2O but dissolves in alkaline solution. [Lewis & Raphael J Chem Soc 4263 1962, Soper et al. J Am Chem Soc 76 4109, Reed & Niu J Am Chem Soc 77 416 1955, Tsuji et al. J Org Chem 43 3606 1978, Calvin Fed Proc USA 13 703 1954.] The S-benzylisothiuronium salt has m 153-154o (evacuated capillary, from MeOH), 132-134o, 135-137o (from EtOH). The dand lforms have m 45-47.5o and [] D 23 ±113o (c 1.88, *C6H6) and have UV in MeOH with max at 330nm ( 140). [Beilstein 19/7 V 237.] The reduced form, (±)-6,8-dimercaptooctanoic acid, [7516-48-5] M 208.3, is a light yellow liquid which is sold in sealed ampoules.

References

[1] GERREKE PH. BIEWENGA  Aalt B  Guido R M M Haenen. The pharmacology of the antioxidant lipoic acid[J]. General Pharmacology-the Vascular System, 1997, 29 3: Pages 315-331. DOI: 10.1016/s0306-3623(96)00474-0
[2] RANDLE P J. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years[J]. Diabetes/Metabolism Research and Reviews, 1999, 14 4: 263-283. DOI: 10.1002/(sici)1099-0895(199812)14:4<263::aid-dmr233>3.0.co;2-c
[3] G BIEWENGA  A B  G R Haenen. The role of lipoic acid in the treatment of diabetic polyneuropathy.[J]. Drug Metabolism Reviews, 1997, 29 4: 1025-1054. DOI: 10.3109/03602539709002242