Abstract: Methods and compositions are provided for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing (SMaRT™) that result in expression of a splicing isoform or variant thereof. The methods and compositions are based upon pre-trans-splicing molecules (PTMs) designed to interact with a target pre-mRNA molecule and mediate a trans-splicing reaction generating a novel chimeric RNA molecule encoding a splicing isoform for the treatment of a variety of gene isoform induced diseases such as cancer.

Abstract: A process for the preparation of N-monosubstituted ?-aminoalcohol sulfonates of formula (1a), (1b): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues; including a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, said organic solvent which can include water to provide N-monosubstituted ?-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and b) asymmetrically hydrogenating.

Abstract: A process for the preparation of N-monosubstituted ?-aminoalcohol sulfonates of formula (1a), (1b): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues; including a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, said organic solvent which can include water to provide N-monosubstituted ?-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and b) asymmetrically hydrogenating.

Abstract: A process for the preparation of N-monosubstituted ?-aminoalcohol sulfonates of formula (Ia), (Ib): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues. The process has the steps of (a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, the organic solvent optionally containing water, to afford N-monosubstituted ?-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and (b) asymmetrically hydrogenating.

Abstract: A salt of a carboxylic acid with an aminoketone of formula II.

Abstract: A salt of a carboxylic acid with an aminoalcohol of formula I.

Abstract: A process for purifying at least one product from a substrate containing at least one product, includes subjecting the substrate to centrifugal partition chromatography in an ion exchange displacement mode to purify the at least one product from the substrate, the at least one product being an amphoteric product.

Abstract: Provided is a process for the preparation of enantiomerically pure 1-substituted-3-aminoalcohols, particularly of (S)-(?)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of formula (II), wherein R1 is selected from the group consisting of 2-thienyl, 2-furanyl and phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein the corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Furthermore provided are salts of a carboxylic acid with said aminoketones and the aminoalcohols obtained by asymmetrically hydrogenating said aminoketones, respectively.

Abstract: Provided is a process for the preparation of enantiomerically pure 1-substituted-3-aminoalcohols, particularly of (S)-(?)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of formula (II), wherein R1 is selected from the group consisting of 2-thienyl, 2-furanyl and phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein the corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Furthermore provided are salts of a carboxylic acid with said aminoketones and the aminoalcohols obtained by asymmetriacally hydrogenating said aminoketones, respectively.

Abstract: A process for the preparation of enantiomerically pure 1-substituted-3-amino-alcohols, particularly of (S)-(?)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of the formula: wherein R1 is 2-thienyl, 2-furanyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups. The corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Salts of a carboxylic acid with the aminoketones and the aminoalcohols obtained by asymmetrically hydrogenating the aminoketones, respectively.

Abstract: Tertiary alcohols are prepared by reacting carboxylic esters with Grignard reagents in ethereal solvents in the presence of lanthanum trichloride and lithium chloride. The method is particularly suitable for the production of (?S)-?-[3-[(1E)-2-(7-chloro-2-quino-linyl)ethenyl]phenyl]-2-(1-hydroxy-1-methylethyl)benzenepropanol of formula (A) which is an intermediate in the production of montelukast.

Abstract: The tertiary alcohol ?-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-2-(1-hydroxy-1-methylethyl)benzene-propanol, the (?S)-enantioner of which is an intermediate in the production of montelukast, is produced by reacting the novel lactone of formula (II) with a methylmagnesium halide in an ethereal solvent in the presence of lanthanum trichloride and lithium chloride. The lactone II can be prepared by reacting a corresponding hydroxyester with a Grignard reagent in the absence of a lanthanoid compound or with a strong base.

Abstract: In one aspect, the present invention relates to a process for the preparation of an optically active alcohol of formula or its mirror image, wherein R1 is unsubstituted or substituted heteroaryl and R2 is phenyl or substituted aryl, by asymmetrically hydrogenating the corresponding ketones in the presence of specific platinum metal complex catalysts, particularly ruthenium.

Abstract: A process for the preparation of N-monosubstituted ?-aminoalcohol sulfonates of formula (Ia), (Ib): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues. The process has the steps of (a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, the organic solvent optionally containing water, to afford N-monosubstituted ?-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and (b) asymmetrically hydrogenating.

Abstract: A process for the preparation of enantiomerically pure 1-substituted-3-amino-alcohols, particularly of (S)-(?)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of the formula: wherein R1 is 2-thienyl, 2-furanyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups. The corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Salts of a carboxylic acid with the aminoketones and the aminoalcohols obtained by asymmetrically hydrogenating the aminoketones, respectively.

Abstract: A process for the preparation of dihydroxypyrimidine derivatives of the general formula: in which R1 and R2 are identical or different and are a hydrogen atom, aryl group, or a C1-C4-alkyl group or an aryl group, starting from a compound of the general formula: in which R2 has the meaning mentioned above and R3 is —CN or COOR4, in which R4 is a C1-C4-alkyl group.

Abstract: A process for the asymmetric hydrogenation of the furoimidazole derivatives of the general formula: ##STR1## wherein R.sub.1 is a protective group, which is cleavable in a known way, and R.sub.2 is hydrogen or a protective group, which is cleavable in a known way, with hydrogen in the presence of a homogeneous catalyst to the corresponding diastereomeric tetrahydrofuroimidazole derivatives of the general formula: ##STR2## The tetrahydrofuroimidazole derivatives of the general formula II are intermediate products for the production of vitamin (+) biotin.

Abstract: A process for the asymmetric hydrogenation of the furoimidazole derivatives of the general formula: ##STR1## wherein R.sub.1 is a protective group, which is cleavable in a known way, and R.sub.2 is hydrogen or a protective group, which is cleavable in a known way, with hydrogen in the presence of a homogeneous catalyst to the corresponding diastereomeric tetrahydrofuroimidazole derivatives of the general formula: ##STR2## The tetrahydrofuroimidazole derivatives of the general formula II are intermediate products for the production of vitamin (+) biotin.

Abstract: .gamma.-Mercaptocarboxylic acids and their derivatives, in particular esters and amides, are prepared from .gamma.-butyrolactones via the corresponding thiolactones. The thiolactones are obtained by reaction of a .gamma.-lactone with thiocarboxylates in polar solvents and are converted by ring opening using nucleophilic reagents, such as, alkali metal alkoxides, into the .gamma.-mercaptocarboxylic acid derivatives. These are intermediates, for example, for the synthesis of leucotriene antagonists.

Abstract: A process for the asymmetric hydrogenation of furoimidazole derivatives of the general formula: ##STR1## wherein R.sub.1 is a protective group and R.sub.2 is hydrogen or a protective group, with hydrogen in the presence of a homogeneous catalyst to give the corresponding diastereomeric dihydrofuroimidazole derivatives of the general formula: ##STR2## The dihydrofuroimidazole derivatives of the general formula II are intermediates for the preparation of the vitamin (+)-biotin.