A previous report showed that the consumption of glutathione through oxidative stress activates the glutathione synthetic pathway, which is accompanied by production of ophthalmic acid from 2-aminobutyric acid (2-AB). We conducted a comprehensive quantification of serum metabolites using gas chromatography-mass spectrometry in patients with atrial septal defect to find clues for understanding myocardial metabolic regulation, and demonstrated that circulating 2-AB levels reflect hemodynamic changes. However, the metabolism and pathophysiological role of 2-AB remains unclear. We revealed that 2-AB is generated by an amino group transfer reaction to 2-oxobutyric acid, a byproduct of cysteine biosynthesis from cystathionine. Because cysteine is a rate-limiting substrate for glutathione synthesis, we hypothesized that 2-AB reflects glutathione compensation against oxidative stress. A murine cardiomyopathy model induced by doxorubicin supported our hypothesis, i.e., increased reactive oxygen species are accompanied by 2-AB accumulation and compensatory maintenance of myocardial glutathione levels. Intriguingly, we also found that 2-AB increases intracellular glutathione levels by activating AMPK and exerts protective effects against oxidative stress. Finally, we demonstrated that oral administration of 2-AB efficiently raises both circulating and myocardial glutathione levels and protects against doxorubicin-induced cardiomyopathy in mice. This is the first study to demonstrate that 2-AB modulates glutathione homeostasis in the myocardium.

A new synthetic method for the preparation of benzofurans has been developed. The key step of this method is the [3,3]‐sigmatropic rearrangement of N‐trifluoroacetyl‐ene‐hydroxylamines, which was triggered by acylation of oxime ethers. TFAA has been proved to be the best reagent to induce [3,3]‐sigmatropic rearrangement for the synthesis of cyclic oracyclic dihydrobenzofurans. On the other hand, the TFAT‐DMAP system is found to be the most effective for constructing various benzofurans. Synthetic utility of this reaction is demonstrated by the short synthesis of natural benzofurans without protection of the hydroxy group. The synthesis of Stemofuran A was accomplished via condensation of ketones with aryloxyamine and subsequent reaction with TFAT‐DMAP in a four‐step synthesis with 72 % overall yield. Similarly, Eupomatenoid 6 and Coumestan were synthesized through the reaction of oxime ether with TFAT‐DMAP. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Alkynyl oxime ether underwent a gold-catalyzed domino reaction involving cyclization and subsequent Claisen-type rearrangement to afford trisubstituted isoxazoles in a direct, efficient, and regioselective manner. The products were successfully applied to the synthesis of unusual heterocycles as an illustration of the potential utility of the reaction.

A new and efficient synthesis of 2-arylbenzofurans has been achieved via a route involving acylation and subsequent [3,3]-sigmatropic rearrangement of oxime ethers. Its synthetic utility is demonstrated by a short synthesis of stemofuran A and eupomatenoid 6 in which no procedure for protection of the phenolic hydroxyl groups is needed. [reaction--see text]

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