Alpha Lipoic Acid The Ultimate Antioxidant
Dec 28, 2015
Alpha Lipoic AcidThe Ultimate Antioxidant
Identity & Structure• “Thioctic acid”• “Lipolate”• (For you IUPAC nerdies): (R/S)-5-(1,2-
dithiolan-3-yl)pentanoic acid
R-AlphaLipoic Acid
S-AlphaLipoic Acid
Dihydro-Lipoic Acid
Alpha Lipoic Acid. University of Maryland Medical Center. https://umm.edu/health/ medical/altmed/supplement/alphalipoic-acid.Maldonado-Rojas, W.; Olivero-Verbel, J.; Ortega-Zuniga, C.; J. Braz. Chem.
Soc. 2011, 22(12), 2250-2259.
Function: Antioxidant• “The Ultimate Antioxidant”• Both water- and fat- soluble• Multiple radical-fighting powers
Antioxidant
Scavenger
ChelateAntioxid
ant
Directly Removes
Free Radicals
Inhibits Free Rad. Generatio
n
Re-enables
Used Antioxidan
ts
ROS MetalRecycler
Rochette, L.; Ghibu, S.; Richard, C.; Zeller, M.; Cottin, Y.; Vergely, C. Molecular Nutrition and Food Research. 2013, 57(1), 114-125. Lipoic Acid. Linus Pauling Institute. Oregon State University. http://lpi.oregonstate.edu/
infocenter/othernuts/la/index.html#safety (accessed March 2, 2014).
R-Alpha Lipoic Acid
Lysine Residue
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.
Lipoic Acid. Linus Pauling Institute. Oregon State University. http://lpi.oregonstate.edu/ infocenter/othernuts/la/index.html#safety. Ziegler D. Treatments in Endocrinology. 2004, 3(3), 173-189.
Eat all the vitamins!
Recommended Amounts• No established dosage
recommendations or upper limit.• No adverse side effects.• Generally, 20-50 mg daily for
antioxidant support.
Alpha Lipoic Acid. University of Maryland Medical Center. https://umm.edu/health/ medical/altmed/supplement/alphalipoic-acid.
Characterization: IR• Broad 3000 cm-1 peak: Carboxylic
Acid• Strong 1700 cm-1 peak: Ring Moiety• Higher than typical aromatic.
SBDS-1H NMR 399.65 MHz. AIST:RIO-DB Spectral Database. http://sdbs.db.aist.go.jp/sdbs/cgi-bin/direct_frame_disp.cgi?sdbsno=52043.
Characterization: H-NMR• 10 Peaks• Splitting indicates hydrocarbon chain.• Group of peaks above 3 consistent
with sulfur.
SBDS-1H NMR 399.65 MHz. AIST:RIO-DB Spectral Database. http://sdbs.db.aist.go.jp/sdbs/cgi-bin/direct_frame_disp.cgi?sdbsno=52043.
Characterization: C-NMR• Shifting Downfield• Carbon 1 with carboxylic acid• Carbons 2, 3, and 4 adjacent to
sulfur atoms
SBDS-1H NMR 399.65 MHz. AIST:RIO-DB Spectral Database. http://sdbs.db.aist.go.jp/sdbs/cgi-bin/direct_frame_disp.cgi?sdbsno=52043.
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, 519-522.
Subhash P.; Kale, Ramesh R.; Pasupathy, K.; Synlett, 2005, 1129-1132.Kim, Hyeon Jin; Kwon, Seung-Ryong; Kim, Kyuwon; Electrochemistry Communications, 2012, v20, 52-55.
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, 1129-1132.Kim, Hyeon Jin; Kwon, Seung-Ryong; Kim, Kyuwon; Electrochemistry Communications, 2012, v20, 52-55.
Synthesis Methods• Method 2:• Tosylhydrazone Degenerations
• Reflux with NaOH• Highly complex• Many byproducts
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 acidEtO
Cl
Cl
O
EtO
SH
SH
O
Na2S, S, H2O
EtO
S
O
S
Bu4N+Br-, MeOH
HO
S
O
S
NaOH, HCl, H2O
Thank You!Alpha Lipoic Acid