American Journal of Clinical Nutrition, Vol 27, 1105-1109, Copyright © 1974 by The American Society for Clinical Nutrition, Inc.

Problems in the stereochemical designation of tocopherals and related compounds

¹ From the Ludwig-Boltzmann-Forschungsstelle für Biochemie, and Institut für Allgemeine Biochemie der Universität Wien, Vienna, Austria

Whereas there are no serious problems concerning the nomenclature and the stereochemical designation of the natural tocopherols and tocotrienols, there exist considerable difficulties in naming the synthetic products with vitamin E activity. These natural compounds and the synthetic materials seem to differ only quantitatively in their biological effects. In the tocopherols, there are three chiral centers, the position 2, 4', and 8'; it is known that in natural -tocopherol the configuration is 2R, 4'R, 8'R. Owing to a slight dextrorotatory effect exhibited by the natural compound on plane-polarized light in certain solvents, it has been called d--tocopherol, whereas the product obtained by condensation of trimethylquinol with natural phytol or phytylbromide, respectively, originally got the name dl--tocopherol. This material is not a racemate but a mixture of the two epimer -tocopherols with the configurations 2R,4'R,8'R and 2S,4'S,8'S. This mixture is probably not equimolar because the mentioned condensation is an asymmetric synthesis that only by chance could lead to the formation of equal amounts of the two epimers. The acetate of this material is the present International Standard for Vitamin E Activity. In recent years a product obtained by condensation of trimethylquinol and synthetic phytol or isophytol, respectively, is extensively used wherever vitamin E activity is desired. This material also has usually been referred to as dl--tocopherol, although it is a mixture of all eight possible stereoisomers in the form of four racemates. Considering the facts that a) the symbols d and dl are not in accord with the present IUPAC-Rules of stereochemistry and b) the old system does not provide distinguishing names for the two, chemically different, synthetic materials having the structure of -tocopherol, a new rational system for the designation of these products is badly needed. We deal here with mixtures of stereoisomers. So far, no system for such mixtures has ever been devised, but the importance of the tocopherols makes the creation of such a system necessary. The IUPAC-IUB Commission on Biochemical Nomenclature proposes the following designations for the most important vitamin E-active materials: a) The natural -tocopherol should be called RRR--tocopherol. b) The diastereoisomer of RRR--tocopherol, being its epimer at C-2, thus having the configuration 2S,4'R,8'R, should be called 2-epi--tocopherol. c) The mixture of RRR--tocopherol and 2-epi--tocopherol, obtained by synthesis using natural phytol or phytylbromide, respectively, should be called 2-ambo--tocopherol. d) The totally synthetic product, obtained by synthesis from synthetic phytol or isophytol, respectively, as starting material, being a mixture of four racemates, should be called all-rac--tocopherol.