Methods for enriching alpha-tocotrienol from mixed tocol compositions
Provided herein are methods for making an alpha-tocotrienol enriched tocol mixture, such as from a plant or plant-derived material. Also provided herein are simulated moving bed purification methods for tocotrienol compounds such as alpha tocotrienol.
1. A method of purifying a tocotrienol from a feed solution comprising the steps of;
a. passing the feed solution through a chromatographic process comprising a stationary phase and a mobile phase stream, wherein said feed solution comprises the tocotrienol and one or more impurity compounds;
b. operating the chromatographic process as a simulated moving bed (SMB) process under conditions effective to purify the tocotrienol from at least one impurity compound;
c. collecting a stream from the SMB apparatus, wherein said stream comprises the purified tocotrienol; and
d. optionally repeating steps a.-c;
wherein the alpha-tocotrienol in the feed stream is prepared according to a method for making an alpha-tocotrienol-enriched tocol mixture, comprising:
(1) contacting a tocol mixture with an amino-alkylating agent, wherein the tocol mixture comprises at least one non-alpha-tocotrienol, at least one non-tocol, optionally alpha-tocotrienol, and optionally one or more tocopherols, whereby the at least one non-alpha-tocotrienol is amino-alkylated;
(2) reducing the amino-alkylated non-alpha-tocotrienols to alpha-tocotrienol with a reducing agent;
(3) removing one or more waxy impurities from the mixture;
(4) contacting the mixture with an agent that binds one or more polar impurities; and
(5) removing the agent that binds one or more polar impurities.
2. The method of claim 1 , wherein the amino-alkylating agent in step (1) comprises a secondary amine and a formaldehyde equivalent.
3. The method of claim 2 , wherein the secondary amine is N-methyl-piperazine.
4. The method of claim 1 , wherein the stream comprising the purified tocotrienol is the extract stream.
5. The method of claim 1 , wherein the stream comprising the purified tocotrienol is the raffinate stream.
6. The method of claim 1 , the stream comprising the purified tocotrienol is the extract stream in a first pass, and wherein the stream comprising the purified tocotrienol is the raffinate stream in a second or subsequent pass.
7. The method of claim 1 , wherein the stream comprising the purified tocotrienol is the raffinate stream in a first pass, and wherein the stream comprising the purified tocotrienol is the extract stream in a second or subsequent pass.
8. The method of claim 1 , wherein the tocotrienol is selected from the group consisting of alpha-tocotrienol, beta-tocotrienol, delta-tocotrienol, and gamma-tocotrienol.
9. The method of claim 8 , wherein the tocotrienol is alpha-tocotrienol.
10. The method of claim 1 , wherein the stationary phase is selected from the group consisting of silica gel, functionalized silica gel, reverse phase gel, or chiral phase gel.
11. The method of claim 1 , wherein the stationary phase has a particle size of about 2 to about 300 μm.
12. The method of claim 1 , wherein the mobile phase stream further comprises one or more solvents selected from the group consisting of: water, acetonitrile, t-AmOH, methanol, ethanol, n-proposal, isopropyl alcohol, butanol, ethyl acetate, isopropyl acetate, MtBE, diethyl ether, fluorinated solvents, alkanes, hexanes, n-hexane, heptanes, n-heptane, methyl-cyclopentane, pentane, methyl-cyclohexane, cyclohexane, toluene, and CO 2 .
13. The method of claim 12 , wherein the mobile phase stream comprises acetonitrile.
14. The method of claim 12 , wherein the mobile phase stream comprises methanol, ethanol, or isopropyl alcohol.
15. The method of claim 1 , wherein the reducing agent in step (2) is sodium cyanoborohydride.
16. The method of claim 1 , wherein a final product stream comprising purified tocotrienol comprises the tocotrienol with at least about 90 (A) % purity.
17. The method of claim 16 , wherein the final product stream comprising purified tocotrienol is concentrated to a tocotrienol concentration of at least about 90 wt %.
18. The method of claim 1 , wherein the chromatographic process comprises 2 to 30 columns serially connected.
19. The method of claim 1 , wherein the chromatographic process is operated at a rate of about 0.05 to about 5 kg feed stream per kg stationary phase per 24 hours.
20. The method of claim 1 , wherein the chromatographic process is operated at a pressure of about 2 bar to about 100 bar.
21. The method of claim 1 , wherein the chromatographic process is operated at a temperature of about 10° C. to about 50° C.
22. The method of claim 1 , wherein the tocol mixture is a palm oil or a material derived from palm oil.
23. The method of claim 1 , further comprising after step (1):
(1)(A) removing water formed from the reaction of step (1).
24. The method of claim 23 , wherein step (1)(A) comprises an azeotropic distillation in the presence of a solvent with a boiling point of at least 95° C. at 1 atm pressure.
25. The method of of claim 24 , wherein the solvent with a boiling point of at least 95° C. at 1 atm pressure is 2-methyl-2-butanol.
26. The method of claim 1 , wherein the solvent of step (2) is 2-methyl-2-butanol.