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Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants.

Jameson VJ, Cochemé HM, Logan A, Hanton LR, Smith RA, Murphy MP - Tetrahedron (2015)

Bottom Line: A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared.The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities.This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.

ABSTRACT

A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared. The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities. This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

No MeSH data available.


Related in: MedlinePlus

Retrosynthetic analysis of MitoEn.
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fig1: Retrosynthetic analysis of MitoEn.

Mentions: The previous synthesis23,25 of MitoE2 involved a large number of steps, was not amenable to the creation of analogues, and was not adaptable to scale-up. Retrosynthetic analysis of a generic MitoEn with chain length n (A) (Fig. 1) shows it can be formed from B by displacement of a leaving group Y. The structure B is the key intermediate in the synthetic scheme as this establishes the basic carbon framework of the target molecule. The substituted heterocyclic ring in B can be derived from 2,3,5-trimethyl-p-hydroquinone (C) and a tertiary allylic alcohol (D) which in turn can be derived from a methyl ketone (E) and a vinyl organometallic species (F). The appropriate methyl ketone (E) can be formed from the corresponding ω-hydroxy alkyne (G).


Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants.

Jameson VJ, Cochemé HM, Logan A, Hanton LR, Smith RA, Murphy MP - Tetrahedron (2015)

Retrosynthetic analysis of MitoEn.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596152&req=5

fig1: Retrosynthetic analysis of MitoEn.
Mentions: The previous synthesis23,25 of MitoE2 involved a large number of steps, was not amenable to the creation of analogues, and was not adaptable to scale-up. Retrosynthetic analysis of a generic MitoEn with chain length n (A) (Fig. 1) shows it can be formed from B by displacement of a leaving group Y. The structure B is the key intermediate in the synthetic scheme as this establishes the basic carbon framework of the target molecule. The substituted heterocyclic ring in B can be derived from 2,3,5-trimethyl-p-hydroquinone (C) and a tertiary allylic alcohol (D) which in turn can be derived from a methyl ketone (E) and a vinyl organometallic species (F). The appropriate methyl ketone (E) can be formed from the corresponding ω-hydroxy alkyne (G).

Bottom Line: A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared.The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities.This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.

ABSTRACT

A series of mitochondria-targeted antioxidants comprising a lipophilic triphenylphosphonium cation attached to the antioxidant chroman moiety of vitamin E by an alkyl linker have been prepared. The synthesis of a series of mitochondria-targeted vitamin E derivatives with a range of alkyl linkers gave compounds of different hydrophobicities. This work will enable the dependence of antioxidant defence on hydrophobicity to be determined in vivo.

No MeSH data available.


Related in: MedlinePlus