1077-28-7 Usage
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
Different sources of media describe the Uses of 1077-28-7 differently. You can refer to the following data:
1. 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.
2. thioctic acid is also known as alpha lipoic acid. It is an anti-oxidant.
3. (±)-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.
4. A fat-metabolism stimulator
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
Notclassified
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.
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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 1077-28-7 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,0,7 and 7 respectively; the second part has 2 digits, 2 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1077-28:
(6*1)+(5*0)+(4*7)+(3*7)+(2*2)+(1*8)=67
67 % 10 = 7
So 1077-28-7 is a valid CAS Registry Number.
1077-28-7Relevant articles and documents
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Bullock et al.
, p. 1828,1830 (1954)
-
A Reagent for Reduction of Disulfide Bonds in Proteins That Reduces Disulfide Bonds Faster Than Does Dithiothreitol
Singh, Rajeeva,Whitesides, George M.
, p. 2332 - 2337 (1991)
We have synthesized a new reagent - N,N'-dimethyl-N,N'-bis(mercaptoacetyl)hydrazine (DMH) - for the reduction of disulfide bonds in proteins.DMH reduces disulfide bonds 7 times faster than does dithiothreitol (DTT) in water at pH 7.DMH reduces mixed disulfides of cysteine proteases (papain and ficin) especially rapidly (30 times faster than DTT).DMH (ε0 = -0.300 V) reduces noncyclic disulfides completely, although it is less strongly reducing than DTT (ε0 = -0.356 V).
-
Thomas,Reed
, p. 5446 (1955)
-
Thiolates of arsenic(III), antimony(III), and bismuth(III) with dl-α-dihydrolipoic acid
Ioannou, Panayiotis V.,Tsivgoulis, Gerasimos M.
, p. 897 - 909 (2014)
Lipoic acid can be reduced to dihydrolipoic acid free of lipoic acid without using deoxygenated solvents. Dihydrolipoic acid reacted with phenylarsine oxide, As2O3, and AsCl3, SbCl 3 but not Sb2O3, and Bi2O 3, BiCl3, and Bi(NO3)3· 5H2O in various solvents giving thiolates. When the reactions were done in methanol, the HCl and HNO3 released caused esterification of the -COOH group. The reaction with As(III) compounds was sensitive to dioxygen, leading to production of lipoic acid derivatives as well, arsenite being particularly active for the autoxidation. Physical (1H NMR) and chemical [reactivity of >M-Cl and >Bi(NO3)] properties of the adducts are described. The six-membered dihydrolipoic acid complexes reacted with stoichiometric amounts of British Anti-Lewisite releasing the dihydrolipoic acid by forming the corresponding complexes of British Anti-Lewisite. Graphical Abstract: [Figure not available: see fulltext.]
Preparation method of R-(+)-lipoic acid
-
Paragraph 0038; 0043; 0044; 0046; 0050; 0052; 0054, (2018/06/23)
The invention discloses a preparation method of R-(+)-lipoic acid. The method comprises the following steps: performing salt formation on a raw material of racemic lipoic acid and a resolving agent ofR-phenylethylamine, so as to obtain diastereoisomeric R-phenylethylamine racemic lipoic acid salt; performing recrystallization separation on a raw material of the salt, so as to obtain a single enantiomer of R-phenylethylamine R-(+)-lipoic acid salt; finally, acidizing the single enantiomer of R-phenylethylamine R-(+)-lipoic acid salt, so as to obtain the target compound R-(+)-lipoic acid in a structure of the formula (I) at a yield of 40%. The method is simple in operation, lower in requirements on equipment, mild in conditions and higher in yield, so that the method is suitable for industrial production.
Chirality induction and chiron approaches to enantioselective total synthesis of α-lipoic acid
Chavan, Subhash P.,Pawar, Kailash P.,Praveen, Ch.,Patil, Niteen B.
, p. 4213 - 4218 (2015/06/02)
Abstract An efficient, short and convenient asymmetric synthesis of (R)-(+)-lipoic acid in seven steps from chiral hydroxy aldehyde with 32.5% overall yield is described. Synthesis of S and R enantiomers of α-lipoic acid from cis-1,4-butene diol derived chiral lactone is reported with 34 % overall yield. The present synthesis involves use of simple reaction conditions making it a convenient synthesis.
