1. The Ultimate Antioxidant
Alpha Lipoic Acid
The Ultimate Antioxidant

2. Identity & Structure R-Alpha S-Alpha Dihydro- Lipoic Acid Lipoic Acid
“Thioctic acid”
“Lipolate”
(For you IUPAC nerdies): (R/S)-5-(1,2-dithiolan-3-yl)pentanoic acid
Alpha Lipoic Acid (ALA), also known as lipoic acid, thioctic acid, lipolate or (R/S)-5-(1,2-dithiolan-3-yl)pentanoic acid, is an antioxidant species made up of a five-carbon carboxylic acid bound to a five-carbon cyclic disulfide. It exists as two enantiomers, R- and S- forms, as well as a reduced form called dihydrolipoic acid (DHLA) in which the disulfide bond is broken into two thiols (Scheme 1).
R-Alpha
S-Alpha
Dihydro-
Lipoic Acid
Lipoic Acid
Lipoic Acid
Alpha Lipoic Acid. University of Maryland Medical Center. medical/altmed/supplement/alphalipoic-acid.
Maldonado-Rojas, W.; Olivero-Verbel, J.; Ortega-Zuniga, C.; J. Braz. Chem. Soc. 2011, 22(12),

3. Function: Antioxidant
“The Ultimate Antioxidant”
Both water- and fat- soluble
Multiple radical-fighting powers
Antioxidant
ROS
Metal
Antioxidant
Scavenger
Chelate
Recycler
ALA primarily functions as a powerful antioxidant, and is uniquely both water- and fat-soluble making it effective throughout the body.1 In this capacity, lipoic acid is able to directly scavenge reactive oxygen species which cause oxidative stress on cell membranes and DNA, and it is also capable of transition metal chelation which inhibits metal-catalyzed generation of free radicals within the body. DHLA is a potent reducing agent, and compounds its effectiveness by recycling other antioxidants such as vitamin C, glutathione, and coenzyme Q-10. 
Directly Removes Free Radicals
Inhibits Free Rad. Generation
Re-enables Used Antioxidants
Rochette, L.; Ghibu, S.; Richard, C.; Zeller, M.; Cottin, Y.; Vergely, C. Molecular Nutrition and Food Research. 2013, 57(1),
Lipoic Acid. Linus Pauling Institute. Oregon State University. infocenter/othernuts/la/index.html#safety (accessed March 2, 2014).

4. Function: Enzyme Cofactor
Biologically active R- enantiomer binds to a specific lysine residue.
Example: Stimulation of glucose metabolism via insulin-signaling pathway.
Effective treatment for type 2 Diabetes.
R-Alpha Lipoic Acid
Lysine Residue
Another important role of ALA is its action as a cofactor for various enzymatic process. This mechanism requires the biologically active R- enantiomer to bind to a specific lysine residue within individual enzyme complexes (Scheme 2).4 One example of this is the stimulation of glucose uptake by lipoic acid's interaction with the insulin-signaling pathway which is sensitive to redox status.3 This makes ALA an effective treatment for type 2 diabetes, in which impaired insulin uptake may lead to vascular disease and peripheral neuropathy.
Lipoic Acid. Linus Pauling Institute. Oregon State University. infocenter/othernuts/la/index.html#safety.
Ziegler D. Treatments in Endocrinology. 2004, 3(3),

5. Recommended Amounts
No established dosage recommendations or upper limit.
No adverse side effects.
Generally, mg daily for antioxidant support.
Eat all the vitamins!
There are currently no established dosage recommendations for alpha-lipoic acid although mg daily is considered adequate to gain general antioxidant support.1 For specific treatment, varying higher doses may be prescribed and doses as high as 1800 mg daily show no adverse side effects, yet there are risks of allergic reactions or harmful drug interactions.4
Alpha Lipoic Acid. University of Maryland Medical Center. medical/altmed/supplement/alphalipoic-acid.

6. Characterization: IR Broad 3000 cm-1 peak: Carboxylic Acid
Strong 1700 cm-1 peak: Ring Moiety
Higher than typical aromatic.
SBDS-1H NMR MHz. AIST:RIO-DB Spectral Database.

7. Characterization: H-NMR
10 Peaks
Splitting indicates hydrocarbon chain.
Group of peaks above 3 consistent with sulfur.
SBDS-1H NMR MHz. AIST:RIO-DB Spectral Database.

8. Characterization: C-NMR
Shifting Downfield
Carbon 1 with carboxylic acid
Carbons 2, 3, and 4 adjacent to sulfur atoms
SBDS-1H NMR MHz. AIST:RIO-DB Spectral Database.

9. Characterization: UV/Vis
Absorbance due to Carboxylic Acid
UV range
203 nm, 302 nm
Goti, P.; Savsani, J.; Patel, P. International Journal of Pharmacy and Pharmaceutical Sciences, 2012, 4,

10. Synthesis Methods Fairly simple compound, Variety of sources.
Easier to synthesize than to extract.
Method 1:
Octanoic Acid
Reflux with Potassium Permanganate
Ethanol solvent
8 Hours
Subhash P.; Kale, Ramesh R.; Pasupathy, K.; Synlett, 2005,
Kim, Hyeon Jin; Kwon, Seung-Ryong; Kim, Kyuwon; Electrochemistry Communications, 2012, v20,

11. Synthesis Methods Method 2: Tosylhydrazone Degenerations
Reflux with NaOH
Highly complex
Many byproducts
Subhash P.; Kale, Ramesh R.; Pasupathy, K.; Synlett, 2005,
Kim, Hyeon Jin; Kwon, Seung-Ryong; Kim, Kyuwon; Electrochemistry Communications, 2012, v20,

12. Synthesis Methods Method 3: (BEST!)
Substitute octanoic acid using Na2S to form thiols
Bu4N+Br- catalyst in methanol to form sulfur ring
Hydrolyze to carboxylic acid

13. Alpha Lipoic Acid
Thank You!