Α-Tocopherol
{{lowercase title}}
{{Chembox
| Watchedfields = changed
| verifiedrevid = 477319727
| Name = α-Tocopherol
| Reference = Merck Index, 11th Edition, 9931.
| ImageFile = Tocopherol, alpha-.svg
| ImageClass = skin-invert-image
| ImageSize = 300px
| ImageFile1 = Vitamin-E-from-xtal-3D-bs-17.png
| ImageClass1 = bg-transparent
| ImageSize1 = 300px
| ImageFile2 = Sample of alpha-tocopherol.jpg
| ImageSize2 = 300px
| PIN = (2R)-2,5,7,8-Tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-1-benzopyran-6-ol
| OtherNames =
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 14265
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 47
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = N9PR3490H9
| InChIKey = GVJHHUAWPYXKBD-IEOSBIPEBS
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C29H50O2/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GVJHHUAWPYXKBD-IEOSBIPESA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 59-02-9
| PubChem = 14985
| EINECS = 200-412-2
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 18145
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00163
| SMILES = Cc1c(O)c(C)c(CC[C@](CCC[C@@H](CCC[C@@H](CCCC(C)C)C)C)(C)O2)c2c1C
| InChI = 1/C29H50O2/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1
}}
|Section2={{Chembox Properties
| Formula = C29H50O2
| MolarMass = 430.71 g/mol
| Appearance = yellow-brown viscous liquid
| Density = 0.950 g/cm3
| MeltingPtC = 2.5 to 3.5
| BoilingPtC = 200 to 220
| BoilingPt_notes = at 0.1 mmHg
| Solubility = insoluble
| SolubleOther = soluble in alcohol, ether, acetone, oils
}}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = A11
| ATCCode_suffix = HA03
}}
|Section7={{Chembox Hazards
| NFPA-H = 1
| NFPA-F = 1
| NFPA-R = 0
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}
α-Tocopherol (alpha-tocopherol) is a type of vitamin E. Its E number is "E307". Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. All feature a chromane ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain, along with an aromatic ring is situated near the carbonyls in the fatty acyl chains of the phospholipid bilayer, allows for penetration into biological membranes.{{cite journal |last1=Burton |first1=G. W. |last2=Ingold |first2=K. U. |title=Vitamin E: application of the principles of physical organic chemistry to the exploration of its structure and function |journal=Accounts of Chemical Research |date=1 June 1986 |volume=19 |issue=7 |pages=194–201 |doi=10.1021/ar00127a001}} It is found most in the membrane's non-raft domains, associated with omega-3 and 6 fatty acids, to partially prevent oxidation.{{cite journal |last1=Atkinson |first1=Jeffrey |last2=Harroun |first2=Thad |last3=Wassall |first3=Stephen R. |last4=Stillwell |first4=William |last5=Katsaras |first5=John |title=The location and behavior of α‐tocopherol in membranes |journal=Molecular Nutrition & Food Research |date=May 2010 |volume=54 |issue=5 |pages=641–651 |doi=10.1002/mnfr.200900439}} The most prevalent form, α-tocopherol, is involved in molecular, cellular, biochemical processes closely related to overall lipoprotein and lipid homeostasis. Compared to the others, α-tocopherol is preferentially absorbed and accumulated in humans.
Vitamin E is found in a variety of tissues, being lipid-soluble, and taken up by the body in a wide variety of ways. Ongoing research is believed to be "critical for manipulation of vitamin E homeostasis in a variety of oxidative stress-related disease conditions in humans."{{cite journal | vauthors = Rigotti A | title = Absorption, transport, and tissue delivery of vitamin E | journal = Molecular Aspects of Medicine | volume = 28 | issue = 5–6 | pages = 423–36 | year = 2007 | pmid = 17320165 | doi = 10.1016/j.mam.2007.01.002 }} One of these disease conditions is the α-tocopherol role in the use by malaria parasites to protect themselves from the highly oxidative environment in erythrocytes.{{cite journal | vauthors = Shichiri M, Ishida N, Hagihara Y, Yoshida Y, Kume A, Suzuki H | title = Probucol induces the generation of lipid peroxidation products in erythrocytes and plasma of male cynomolgus macaques | journal = Journal of Clinical Biochemistry and Nutrition | volume = 64 | issue = 2 | pages = 129–142| year = 2019 | pmid = 30936625 |pmc = 6436040 | doi = 10.3164/jcbn.18-7}} A second of these disease conditions is the α-tocopherol antioxidant properties' role cardiovascular heart disease. In preventing LDL (low-density lipoprotein) oxidation, it is able to decrease chances of atherosclerosis and arterial build-up.{{cite journal |last1=Singh |first1=U. |last2=Devaraj |first2=S. |last3=Jialal |first3=I. |title=VITAMIN E, OXIDATIVE STRESS, AND INFLAMMATION |journal=Annual Review of Nutrition |date=21 August 2005 |volume=25 |issue=1 |pages=151–174 |doi=10.1146/annurev.nutr.24.012003.132446}}
Synthesis
To synthesize the ⍺-diastereomer selectively, tocol acetate is transformed to the naturally occurring, kinetically favored α-tocopherol after being catalyzed by the lipase enzyme. This reaction occurs under biological conditions, commonly in the digestive system.{{cite journal |last1=Mizuguchi |first1=Eisaku |last2=Takemoto |first2=Masumi |last3=Achiwa |first3=Kazuo |title=An enzyme-catalyzed synthesis of natural α-tocopherol |journal=Tetrahedron: Asymmetry |date=January 1993 |volume=4 |issue=9 |pages=1961–1964 |doi=10.1016/s0957-4166(00)82239-9}}
Stereoisomers
α-Tocopherol has three stereocenters, so it is a chiral molecule.{{cite journal | vauthors = Jensen SK, Lauridsen C | title = Alpha-tocopherol stereoisomers | journal = Vitamins and Hormones | volume = 76 | pages = 281–308 | year = 2007 | pmid = 17628178 | doi = 10.1016/S0083-6729(07)76010-7 | isbn = 9780123735928 }} The eight stereoisomers of α-tocopherol differ in the configuration of these stereocenters. RRR-α-tocopherol is the natural one.{{cite journal | vauthors = Brigelius-Flohé R, Traber MG | title = Vitamin E: function and metabolism | journal = FASEB Journal | volume = 13 | issue = 10 | pages = 1145–55 | date = July 1999 | pmid = 10385606 | doi = 10.1096/fasebj.13.10.1145 | s2cid = 7031925 | url = http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=10385606 | doi-access = free }} The older name of RRR-α-tocopherol is d-α-tocopherol, but this d/l naming should no longer be used, because whether l-α-tocopherol should mean SSS enantiomer or the SRR diastereomer is not clear, from historical reasons. The SRR may be named 2-epi-α-tocopherol, the diastereomeric mixture of RRR-α-tocopherol and 2-epi-α-tocopherol may be called 2-ambo-α-tocopherol (formerly named dl-α-tocopherol). The mixture of all eight diastereomers is called all-rac-α-tocopherol.[https://web.archive.org/web/20201122071533/https://www.qmul.ac.uk/sbcs/iupac/misc/toc.html IUPAC Nomenclature of Tocopherols and Related Compounds], from https://www.degruyter.com/document/doi/10.1351/pac198254081507/pdf The α-Tocopherol is the most active diastereomer biologically, while being maintained at a high level in plasma and tissues of many different animal species.{{cite journal |last1=Jensen |first1=Søren K. |last2=Nørgaard |first2=Jan V. |last3=Lauridsen |first3=Charlotte |title=Bioavailability of α-tocopherol stereoisomers in rats depends on dietary doses of all-rac - or RRR-α-tocopheryl acetate |journal=British Journal of Nutrition |date=March 2006 |volume=95 |issue=3 |pages=477–487 |doi=10.1079/bjn20051667 |url=https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/bioavailability-of-tocopherol-stereoisomers-in-rats-depends-on-dietary-doses-of-allrac-or-rrrtocopheryl-acetate/921CFDBA1B7B2923CD5937F2069BE1BA |access-date=31 October 2024}}
One IU of tocopherol is defined as {{frac|2|3}} milligram of RRR-α-tocopherol (formerly named d-α-tocopherol). 1 IU is also defined as 0.9 mg of an equal mix of the eight stereoisomers, which is a racemic mixture, all-rac-α-tocopheryl acetate. This mix of stereoisomers is often called dl-α-tocopheryl acetate.{{cite web|archive-url=https://web.archive.org/web/20120219164132/http://www.nal.usda.gov/fnic/foodcomp/Data/SR20/SR20_doc.pdf |archive-date=2012-02-19 |url=https://www.ars.usda.gov/ARSUserFiles/80400525/Data/SR20/SR20_doc.pdf |title=Composition of Foods Raw, Processed, Prepared USDA National Nutrient Database for Standard Reference, Release 20 |publisher=USDA |date=February 2008 |url-status=dead }} Starting with May 2016, the IU unit is made obsolete, such that 1 mg of "Vitamin E" is 1 mg of d-alpha-tocopherol or 2 mg of dl-alpha-tocopherol.{{cite web |title=Unit Conversions |url=https://dietarysupplementdatabase.usda.nih.gov/Conversions.php |publisher=National Institutes of Health |access-date=2018-11-21}}