Proof that the absolute configuration of natural α-lipoic acid is R by the synthesis of its enantiomer [(S)-(–)-α-lipoic acid] from (S)-malic acid

Brookes, Michael H.; Golding, Bernard T.; Howes, D. A.; Hudson, A. T.

doi:10.1039/c39830001051

Cited by 39 publications

(19 citation statements)

References 1 publication

(1 reference statement)

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“…R -α-lipoic acid (RLA) is biosynthesized from octanoic acid in mitochondria [ 8 , 9 , 10 , 11 ]. It is a natural form of LA [ 12 ], and works as a cofactor of various mitochondrial respiratory chain enzymes such as pyruvate, α-ketoglutarate, and branched-chain α-ketoacid dehydrogenases [ 13 ]. Both forms of LA seem to have different potencies.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

Uchida

Okamoto

Ikuta

et al. 2015

IJMS

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α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C0), AUC, and half-life (T1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg) and hepatic availability (Fh), and not from the total clearance.

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Section: Introductionmentioning

confidence: 99%

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

Uchida

Okamoto

Ikuta

et al. 2015

IJMS

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“…Under normal physiological conditions, it is supplied by biosynthesis and food ingestion. On the other hand, S-α-lipoic acid (SLA) is not a naturally occurring compound [ 8 ]. Both forms seem to have different potencies.…”

Section: Introductionmentioning

confidence: 99%

Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats

Uchida

Iwamoto

Nagayama

et al. 2015

IJMS

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R-α-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of RLA with α-, β- or γ-cyclodextrins (CD) were prepared and orally administered as a suspension to rats. Among them, RLA/γ-CD showed the highest plasma exposure, and its area under the plasma concentration-time curve (AUC) of RLA was 2.2 times higher than that after oral administration of non-inclusion RLA. On the other hand, the AUC after oral administration of non-inclusion RLA and RLA/γ-CD to pylorus-ligated rats did not differ. However, the AUC after intraduodenal administration of RLA/γ-CD was 5.1 times higher than that of non-inclusion RLA, and was almost comparable to the AUC after intraduodenal administration of RLA-Na solution. Furthermore, the AUC after intraduodenal administration of RLA/γ-CD was not affected by biliary ligation or co-administration of an amylase inhibitor. These findings demonstrated that RLA was absorbed from the small intestine effectively when orally administered as a γ-CD inclusion complex, which could be easily dissolved in the lumen of the intestine. In conclusion, γ-CD inclusion complex is an appropriate formulation for supplying RLA as a drug or nutritional supplement with respect to absorption.

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“…As an important cofactor involved in many enzyme-catalyzed reactions [1], α-lipoic acid has already been used to treat many diseases [2,3,4]. Since ( R )-α-lipoic acid exhibits higher biological activity than its ( S )-enantiomer [5], great attention has been focused on the stereoselective synthesis of its ( R )-enantiomer. There are two main routes to synthesize ( R )-α-lipoic acid, including the chemical synthesis and biocatalytic process.…”

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted Resolution of α-Lipoic Acid Catalyzed by an Ionic Liquid Co-Lyophilized Lipase

Liu

Wang

et al. 2015

Molecules

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Abstract:The combination of the ionic liquid co-lyophilized lipase and microwave irradiation was used to improve enzyme performance in enantioselective esterification of α-lipoic acid. Effects of various reaction conditions on enzyme activity and enantioselectivity were investigated. Under optimal condition, the highest enantioselectivity (E = 41.2) was observed with a high enzyme activity (178.1 μmol/h/mg) when using the ionic liquid co-lyophilized lipase with microwave assistance. Furthermore, the ionic liquid co-lyophilized lipase exhibited excellent reusability under low power microwave.

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Proof that the absolute configuration of natural α-lipoic acid is R by the synthesis of its enantiomer [(S)-(–)-α-lipoic acid] from (S)-malic acid

Cited by 39 publications

References 1 publication

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats

Microwave-Assisted Resolution of α-Lipoic Acid Catalyzed by an Ionic Liquid Co-Lyophilized Lipase

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