Abstract:
Vitamin E is considered as the most effective lipophilic chain breaking
antioxidant. a-Tocopherol and its analogues have been studied thoroughly with
regards to its biokinetics and bioavailabily. Deuterated tocopherols have been
synthesized and utilized in such studies. Tocotrienols are arousing more and more
interest because of their high efficiency as antioxidants. However, to date, there is no
effective synthetic method reported for deuterated tocotrienols.
This thesis is focused on the investigation of the synthetic methods of deuterated
tocotrienols and their analogues: 5-trideuteromethyl-a-tocotrienol, 5-
trideuteromethyl-p-tocotrienol, tocotrienol acetate, silyl tocotrienol ether,
etc. Several synthetic procedures for the preparation of poly-deuterated tocopherols
are known. Mainly the deuterium is introduced by use of labelled formaldehyde and
deuterated hydrogen chloride under Lewis acid catalysis. However, these methods are
not effective in tocotrienols due to exchange of protons for deuterium at other sites
under the acidic conditions. We developed several different approaches to generate
polydeuterated tocotrienols by using both morpholinomethylation followed by
reduction with NaCNBDs as deuterated reducing reagents and transmetalation
strategy. The 5-trideuteromethyl-a-tocotrienol was finally obtained in a satisfactory
yield of 60%. In addition, this thesis also discussed the study of structural
comparison and the chemical property difference of tocopherols and tocotrienols,
which provides hints to explain the reactivity difference of them towards oxidation at
the C3-C4 positions.Furthermore, the methodology of halogenation and dehydrohalogenation of
tocotrienol was explored to prepare a hexaene tocotrienol derivative as a florescent
reporter of tocopherol.
