The present invention relates to the calcium complex of (4RS)(4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl oxa-5,8,11-triazatridecan-13-oato(5-))pentahydrogen (BOPTA) in the form of a salt, to the process for its preparation and to a formulation comprising said salt.

The present invention relates to the calcium complex of (4RS)(4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl oxa-5,8,11-triazatridecan-13-oato(5-))pentahydrogen (BOPTA) in the form of a salt, to the process for its preparation and to a formulation comprising said salt.

A relaxation formulation structured to induce a deep state of relaxation in a person comprises amounts of tryptophan, melatonin, vitamin B3, and vitamin B6. Another relaxation formulation also includes an amount of tyrosine, and yet another formulation includes an amount of vitamin B12. At least one embodiment of a relaxation formula comprises a physiologically effective amount of gamma-aminobutyric acid (“GABA”). A delivery system is provided to facilitate administration of the relaxation formulation to a person. The delivery system may include an edible high carbohydrate matrix, such as a chocolate brownie. Alternatively, the delivery system may comprise an inert vaporizable compound to allow the components of the relaxation formulation to be inhaled directly into the lungs of a person. Other delivery systems include an aqueous sublingual spray and a beverage.

A relaxation formulation structured to induce a deep state of relaxation in a person comprises amounts of tryptophan, melatonin, vitamin B3, and vitamin B6. Another relaxation formulation also includes an amount of tyrosine, and yet another formulation includes an amount of vitamin B12. At least one embodiment of a relaxation formula comprises a physiologically effective amount of gamma-aminobutyric acid (“GABA”). A delivery system is provided to facilitate administration of the relaxation formulation to a person. The delivery system may include an edible high carbohydrate matrix, such as a chocolate brownie. Alternatively, the delivery system may comprise an inert vaporizable compound to allow the components of the relaxation formulation to be inhaled directly into the lungs of a person. Other delivery systems include an aqueous sublingual spray and a beverage.

The present invention relates to novel Ruthenium complexes of formulae A1-A4 and their use, inter alia, for (1) dehydrogenative coupling of alcohols to esters; (2) hydrogenation of esters to alcohols (including hydrogenation of cyclic esters (lactones) or cyclic di-esters (di-lactones), or polyesters); (3) preparing amides from alcohols and amines—(including the preparation of polyamides (e.g., polypeptides) by reacting dialcohols and diamines and/or polymerization of amino alcohols and/or forming cyclic dipeptides from p-aminoalcohols; (4) hydrogenation of amides (including cyclic dipeptides, polypeptides and polyamides) to alcohols and amines; (5) hydrogenation of organic carbonates (including polycarbonates) to alcohols or hydrogenation of carbamates (including polycarbamates) or urea derivatives to alcohols and amines; (6) dehydrogenation of secondary alcohols to ketones; (7) amidation of esters (i.e., synthesis of amides from esters and amines); (8) acylation of alcohols using esters; (9) coupling of alcohols with water and a base to form carboxylic acids; and (10) preparation of amino acids or their salts by coupling of amino alcohols with water and a base. The present, invention further relates to the use of certain known Ruthenium complexes for the preparation of amino acids or their salts from amino alcohols.

The present invention relates to novel Ruthenium complexes of formulae A1-A4 and their use, inter alia, for (1) dehydrogenative coupling of alcohols to esters; (2) hydrogenation of esters to alcohols (including hydrogenation of cyclic esters (lactones) or cyclic di-esters (di-lactones), or polyesters); (3) preparing amides from alcohols and amines—(including the preparation of polyamides (e.g., polypeptides) by reacting dialcohols and diamines and/or polymerization of amino alcohols and/or forming cyclic dipeptides from p-aminoalcohols; (4) hydrogenation of amides (including cyclic dipeptides, polypeptides and polyamides) to alcohols and amines; (5) hydrogenation of organic carbonates (including polycarbonates) to alcohols or hydrogenation of carbamates (including polycarbamates) or urea derivatives to alcohols and amines; (6) dehydrogenation of secondary alcohols to ketones; (7) amidation of esters (i.e., synthesis of amides from esters and amines); (8) acylation of alcohols using esters; (9) coupling of alcohols with water and a base to form carboxylic acids; and (10) preparation of amino acids or their salts by coupling of amino alcohols with water and a base. The present, invention further relates to the use of certain known Ruthenium complexes for the preparation of amino acids or their salts from amino alcohols.

The present invention involves preparing compounds represented by the following formula:

##STR00001##

from a compound of the following formula:

##STR00002##

In these formulae: R.sup.1 represents a Br group, an iodine group, a Cl group, an NO.sub.2 group, or an NH.sub.2 group; R.sup.2 represents a halogen group, an NO.sub.2 group, an NH.sub.2 group, Sn(R.sup.6).sub.3, N═N—NR.sup.7R.sup.8, OSO.sub.2R.sup.9, N R.sup.10R.sup.11, phenyliodonium, a heterocyclic group iodine, boric acid, or a borate ester; R.sup.30 represents a protective group PG.sup.1; R.sup.40 or R.sup.50 represent hydrogen, a protective group PG.sup.2, or C.sub.6H.sub.5(C.sub.6H.sub.5)C═N, in which NR.sup.40R.sup.50 are together.

The present invention involves preparing compounds represented by the following formula:

##STR00001##

from a compound of the following formula:

##STR00002##

In these formulae: R.sup.1 represents a Br group, an iodine group, a Cl group, an NO.sub.2 group, or an NH.sub.2 group; R.sup.2 represents a halogen group, an NO.sub.2 group, an NH.sub.2 group, Sn(R.sup.6).sub.3, N═N—NR.sup.7R.sup.8, OSO.sub.2R.sup.9, N R.sup.10R.sup.11, phenyliodonium, a heterocyclic group iodine, boric acid, or a borate ester; R.sup.30 represents a protective group PG.sup.1; R.sup.40 or R.sup.50 represent hydrogen, a protective group PG.sup.2, or C.sub.6H.sub.5(C.sub.6H.sub.5)C═N, in which NR.sup.40R.sup.50 are together.

Provided is a stable isotope-labeled aliphatic amino acid enabling the assignment of the signal of an amino acid residue side chain by increasing to the maximum the observation sensitivity to an NMR signal of the same amino acid residue side chain, and allowing NOE (nuclear Overhauser effect) between protons in the amino acid residue to be observed. The stable isotope-labeled aliphatic amino acid is for constituting a protein and satisfies all of the following conditions (1) to (3): (1) two or more carbon atoms are labeled with .sup.13C; (2) of two or more carbon atoms labeled with .sup.13C, a carbon atom other than a carbon atom of a methyl group, which is capable of bonding to a hydrogen atom, has one .sup.1H directly bonded thereto, while the carbon atom of the methyl group has at least one .sup.1H directly bonded thereto; and (3) other carbon atoms adjacent to all the .sup.13C are all .sup.12C.

Provided is a stable isotope-labeled aliphatic amino acid enabling the assignment of the signal of an amino acid residue side chain by increasing to the maximum the observation sensitivity to an NMR signal of the same amino acid residue side chain, and allowing NOE (nuclear Overhauser effect) between protons in the amino acid residue to be observed. The stable isotope-labeled aliphatic amino acid is for constituting a protein and satisfies all of the following conditions (1) to (3): (1) two or more carbon atoms are labeled with .sup.13C; (2) of two or more carbon atoms labeled with .sup.13C, a carbon atom other than a carbon atom of a methyl group, which is capable of bonding to a hydrogen atom, has one .sup.1H directly bonded thereto, while the carbon atom of the methyl group has at least one .sup.1H directly bonded thereto; and (3) other carbon atoms adjacent to all the .sup.13C are all .sup.12C.