In the past, optically active alpha-tocooherol and derivatives thereof which are the 2R,4'R,8'R isomers of compounds of the formula: ##STR1## have been prepared through isolation from natural sources such as vegetable oil. This procedure suffers from many drawbacks due to the fact that the tocopherol content of these oils is very small. Therefore, a great amount of oil must be processed in order to isolate a small amount of natural tocopherol. Additionally, the process whereby various tocopherols are isolated from vegetable oil is extremely cumbersome.
In U.S. patent application Ser. No. 417,465, filed Nov. 19, 1973, Scott et al., vitamin E active compounds have been synthesized by utilizing a compound of the formula: ##STR2## wherein R forms with its attached oxygen moiety an ether protecting group removable by hydrogenolysis or acid catalyzed cleavage; and
R' is lower alkyl; and a compound of the formula: ##STR3## The compound of formula II can be a racemate or a 2R or 2S isomer, depending upon the desired isomeric form of the compound of formula I. (Please note, the compound of the formula VII in U.S. patent application Ser. No. 417,465, filed Nov. 19, 1973). PA1 X is a halogen; or a compound of the formula: ##STR6## via the condensation of a compound of the formula: ##STR7## wherein R and X are as above, with a compound of the formula: ##STR8## wherein A and B are hydrogen or taken together form a carbon to carbon bond; or via the condensation of a compound of the formula: ##STR9## with a compound of the formula: ##STR10## wherein A and B are as above; PA1 one of R.sub.4 or R.sub.5 is --CH.sub.2 MgX and the other is --CH.sub.2 OR.sub.6 ; PA1 X is as above; PA1 --OR.sub.6 is a leaving group; PA1 and m and n are integers from 0 to 1 with the proviso that the sum of m and n is equal to 1. PA1 R.sub.1 ' taken together with its attached oxygen atoms forms an ether protecting group removable by acid catalyzed cleavage. PA1 R', taken together with its attached oxygen atom forms an ether protecting group removable by acid catalyzed cleavage.
The compound of formula III can also be a racemate or various 2 and 5, R and S isomers. (Please note compound XLIV in U.S. patent application Ser. No. 417,465, filed Nov. 19, 1973). Where the compound of the formula III has a 2R, 6R configuration, i.e., a compound of the formula: ##STR4## then natural .alpha.-tocopherol is produced when the compound of the formula III-A and the 2S isomer of the compound of formula II are utilized.
In accordance with this process, it has been desired to provide a simple and economic method for preparing the compound of formula III and III-A, natural vitamin E and isomers derived therefrom from relatively cheap and economic starting materials.
USPTO Backgrounds
USPTO Backgrounds