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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

Synthesis of key hydroxychromans for MitoE2, MitoE4 and MitoE6. Reagents and conditions: a HgO, Tf2O, CH3CN (10 min), tetramethylurea (5 min), H2O, CH2Cl2; b DHP, PPTS, CH2Cl2; c vinylMgCl, THF; d HCOOH, 10, reflux.
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sch1: Synthesis of key hydroxychromans for MitoE2, MitoE4 and MitoE6. Reagents and conditions: a HgO, Tf2O, CH3CN (10 min), tetramethylurea (5 min), H2O, CH2Cl2; b DHP, PPTS, CH2Cl2; c vinylMgCl, THF; d HCOOH, 10, reflux.

Mentions: The synthesis of MitoE6 (3) (Scheme 2), will be described in detail as an exemplar of the methodology. For this the required ω-hydroxy alkyne, 6-octyn-1-ol, (6) was treated with Hg(OTf)2·(TMU)2 in aqueous CH3CN34 to afford 8-hydroxy-2-octanone (7) in 95% yield (Scheme 1). The primary hydroxyl group was then converted into a THP ether (8) in 86% yield followed by reaction with vinylmagnesium chloride to readily afford the tertiary allylic alcohol 9, following chromatography with 0.1% Et3N in the elutant, in 96% yield. Reaction of 9 with 2,3,5-trimethyl-p-hydroquinone (10) in acid35—preferably formic acid36—afforded diol 11 in 53% yield.


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

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

Synthesis of key hydroxychromans for MitoE2, MitoE4 and MitoE6. Reagents and conditions: a HgO, Tf2O, CH3CN (10 min), tetramethylurea (5 min), H2O, CH2Cl2; b DHP, PPTS, CH2Cl2; c vinylMgCl, THF; d HCOOH, 10, reflux.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

sch1: Synthesis of key hydroxychromans for MitoE2, MitoE4 and MitoE6. Reagents and conditions: a HgO, Tf2O, CH3CN (10 min), tetramethylurea (5 min), H2O, CH2Cl2; b DHP, PPTS, CH2Cl2; c vinylMgCl, THF; d HCOOH, 10, reflux.
Mentions: The synthesis of MitoE6 (3) (Scheme 2), will be described in detail as an exemplar of the methodology. For this the required ω-hydroxy alkyne, 6-octyn-1-ol, (6) was treated with Hg(OTf)2·(TMU)2 in aqueous CH3CN34 to afford 8-hydroxy-2-octanone (7) in 95% yield (Scheme 1). The primary hydroxyl group was then converted into a THP ether (8) in 86% yield followed by reaction with vinylmagnesium chloride to readily afford the tertiary allylic alcohol 9, following chromatography with 0.1% Et3N in the elutant, in 96% yield. Reaction of 9 with 2,3,5-trimethyl-p-hydroquinone (10) in acid35—preferably formic acid36—afforded diol 11 in 53% yield.

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