The invention relates to methods of separating Trolox isomers (R)-Trolox and (S)-Trolox, comprising: (a) contacting a mixture of (R) and (S)-Trolox with a resolving agent selected from the group consisting of (1S,2S)-(+)-Pseudoephedrine, (R)-(+)-2-Amino-3-phenyl-1-propanol, (1R,2R)-(−)-Pseudoephedrine, and (S)-(−)-2-Amino-3-phenyl-1-propanol, wherein the resolving agent forms a solid salt with one of (R)-Trolox and (S)-Trolox, and substantially does not form a solid salt with the other; and (b) separating the solid salt from the Trolox isomer that did not form the solid salt with the resolving agent.

The invention relates to methods of separating Trolox isomers (R)-Trolox and (S)-Trolox, comprising: (a) contacting a mixture of (R) and (S)-Trolox with a resolving agent selected from the group consisting of (1S,2S)-(+)-Pseudoephedrine, (R)-(+)-2-Amino-3-phenyl-1-propanol, (1R,2R)-(−)-Pseudoephedrine, and (S)-(−)-2-Amino-3-phenyl-1-propanol, wherein the resolving agent forms a solid salt with one of (R)-Trolox and (S)-Trolox, and substantially does not form a solid salt with the other; and (b) separating the solid salt from the Trolox isomer that did not form the solid salt with the resolving agent.

The present invention provides a method for chiral resolution of Trolox. The present disclosure relates to a method for producing a solid salt of a compound of formula I, wherein an amide-based solvent is added to a sample, which contains a compound of formula I, while being assumed to contain a compound of formula II, in the presence of an optical resolution agent:

##STR00001## Formula I: (R)-6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (hereinafter referred to R Trolox)

##STR00002## Formula II: (S)-6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (hereinafter referred to S Trolox).

The present invention provides a method for chiral resolution of Trolox. The present disclosure relates to a method for producing a solid salt of a compound of formula I, wherein an amide-based solvent is added to a sample, which contains a compound of formula I, while being assumed to contain a compound of formula II, in the presence of an optical resolution agent:

##STR00001## Formula I: (R)-6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (hereinafter referred to R Trolox)

##STR00002## Formula II: (S)-6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (hereinafter referred to S Trolox).

The invention relates to novel compounds that are useful for modulating cellular ROS. The compounds are amide-derivatives of 2-hydroxy-2-methyl-4-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-butanoic acid. The compounds of the invention are formulated into pharmaceutical or cosmetic compositions. The invention further relates to methods wherein the compounds of the invention are used for treating or preventing diseases associated with increased ROS levels mitochondrial disorders and/or conditions associated with mitochondrial dysfunction, including adverse drug effects. The invention also relates to cosmetic methods for treating or delaying further aging of the skin and veterinary applications.

The invention relates to novel compounds that are useful for modulating cellular ROS. The compounds are amide-derivatives of 2-hydroxy-2-methyl-4-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-butanoic acid. The compounds of the invention are formulated into pharmaceutical or cosmetic compositions. The invention further relates to methods wherein the compounds of the invention are used for treating or preventing diseases associated with increased ROS levels mitochondrial disorders and/or conditions associated with mitochondrial dysfunction, including adverse drug effects. The invention also relates to cosmetic methods for treating or delaying further aging of the skin and veterinary applications.

The invention relates to certain chromanol, quinone or hydroquinone compounds and derivatives thereof for treatment of sepsis and sepsis-induced organ dysfunction. Specifically, the present invention relates to chromanol compounds chosen from S-(6-hydroxy-2,5,7,8-tetramethylchroman-2yl)(piperazin-1-yl)methanone and S-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone, and pharmaceutically acceptable salts thereof.

The invention relates to certain chromanol, quinone or hydroquinone compounds and derivatives thereof for treatment of sepsis and sepsis-induced organ dysfunction. Specifically, the present invention relates to chromanol compounds chosen from S-(6-hydroxy-2,5,7,8-tetramethylchroman-2yl)(piperazin-1-yl)methanone and S-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(4-(2-hydroxyethyl)piperazin-1-yl)methanone, and pharmaceutically acceptable salts thereof.

The invention relates to amide-derivatives of 2-hydroxy-2-methyl-4-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-butanoic acid for use in a treatment for preventing or suppressing symptoms mediated by enhanced mPGES-1 expression or activity. In particular the invention relates the use of these compounds for treating diseases and conditions in which the inhibition of the enzyme mPGES-1 activity and/or expression would be beneficial such as inflammatory diseases, nociceptive pain, auto-immune diseases, breathing disorders, fever, cancer, inflammation related anorexia, Alzheimer's disease and cardiovascular disease.

Methods, compositions, and kits are provided for synthesizing bioactive chromane, the method including: constructing a tertiary ether stereocenter enantioselectively by catalyzed alkynylation of a substituted chromenone to obtain a chromanone; reducing alkyne and ketone in the chromanone to obtain a chroman; and converting ester to methyl group thereby obtaining chromane.