Abstract: This invention relates to the purification of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester by slurrying a mixture containing N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester with organic or aqueous organic solvents.

Abstract: N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester is produced by hydrogenation of a mixture of 3,3-dimethylbutyraldehyde and a precursor of L-&agr;-aspartyl-L-phenylalanine 1-methyl ester. In particular, N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester is produced using an acid salt of L-&agr;-aspartyl-L-phenylalanine 1-methyl ester or N-protected L-&agr;-aspartyl-L-phenylalanine 1-methyl ester. The production method is efficient and low cost, as compared with conventional N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester synthesis.

Abstract: There is provided a novel mixed crystal comprising aspartame (APM) and N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine methyl ester, which can be used as a sweetener having considerably improved quality of sweetness, etc. The above mixed crystal can be easily produced industrially by subjecting a solution containing the above-mentioned APM and APM derivative to a crystallizing operation followed by the separation of the mixed crystal thus precipitated.

Abstract: N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester is produced using novel oxazolidinone derivatives.

Abstract: In the separation and purification of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine methyl ester produced in the reductive alkylation of aspartame (APM) with 3,3-dimethylbutylaldehyde, the APM used in the starting material for the alkylation, which is difficult to be separated by recrystallization only from the crude crystals of the reaction product, can be separated and removed by extraction or solution thereof with the specified organic solvent from the concentrated reaction solution of the reductive alkylation or from the crude crystals of the product therefrom, and further N,N-di(3,3-dimethylbutyl)-APM as the by-product can be separated and removed by means for separation and purification, such as crystallization, chromatography, extraction, treatment with the activated charcoal, etc.

Abstract: A purified N-t-butoxycarbonylphenylalanine ester preparation having an enhanced optical activity can be obtained by bringing an N-t-butoxycarbonylphenylalanine ester preparation containing an optically active compound into contact with an aliphatic hydrocarbon, extracting the optically active compound with the aliphatic hydrocarbon, and recovering the optically active compound from the resulting extract.

Abstract: A novel amorphous N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester compound is disclosed. Also disclosed are processes for preparing the compound. The novel compound has improved solubility and dissolution properties compared to the known monohydrate.

Abstract: The invention includes selected novel optically active &agr;-ketones which either are themselves useful or are intermediates for the preparation of known ketomethylene pseudopeptides useful as antibiotics, antibiotic enhancers, or enzyme inhibitors. Further, the present invention provides a method for dehydrogenation/asymmetrical hydrogenation to obtain essentially pure antipodes of ketomethylene pseudopeptides having two chiral centers.

Abstract: There is provided a process for purification of N-(3,3-dimethylbutyl)-&agr;-L-aspartyl-L-phenylalanine methyl ester comprising the step of contacting impure N-(3,3-dimethylbutyl)-&agr;-L-aspartyl-L-phenylalanine methyl ester containing at least &agr;-L-aspartyl-L-phenylalanine methyl ester as an impurity, with the mixed solvents having two layers of one layer given from at least one organic solvent which does not mix with water homogeneously and one layer of water to extract N-(3,3-dimethylbutyl)-&agr;-L-aspartyl-L-phenylalanine methyl ester in the organic solvent layer. In the present invention, the desired compound can be purified or recovered efficiently in a high yield without using burdensome steps or operations.

Abstract: The invention provides a method of preparing new crystal forms of aspartame utilizing microemulsions comprising: (a) introducing aspartame into a microemulsion formed from an oil phase, an aqueous phase and at least one emulsifier, (b) destabilizing the microemulsion to effect recrystallization of aspartame; (c) separating solid phase crystals from the liquid phase in which they are contained; and (d) cleaning the crystals to remove traces of the oil phase and surfactant.

Abstract: The invention relates to an improved process for the preparation of neotame by successively

Abstract: Dipeptide sweeteners are disclosed that are basic salts of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester represented by the formula wherein Xm+ is selected from the group consisting of Na+, K+, Al3+, Fe2+, Fe3+, Ca2+, Mg2+, NH4+ and Zn2+; Qs− absent or a physiologically acceptable counter anion; and m−s=n. Also disclosed is a liquid low-calorie sweetener containing such basic salts.

Abstract: A process for preparing 2-amino malonic acid derivatives of formula (1): wherein A is linear or branched chain alkylene having from 1 to 10 carbon atoms, R1 is linear or branched chain alkyl having from 2 to 20 carbon atoms, R2 and R3 are the same or different, and are lower alkyl or aralkyl, and R4 is a protecting group, which process comprises the steps of reducing a compound of formula (6): wherein A is linear or branched chain alkylene having from 1 to 10 carbon atoms, R1 is linear or branched chain alkyl having from 2 to 20 carbon atoms, R2 and R3 are the same or different, and are lower alkyl or aralkyl, and R4 is a protecting group.

Abstract: N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester is produced by reductive alkylation and crystallization/isolation in methanol and water. The production method is efficient and low cost, as compared with conventional N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester synthesis and results in high purity N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester.

Abstract: A process for preparing 2-amino malonic acid derivatives of formula (1): 1

Abstract: A novel class of tripeptide &agr;-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M1—AA—AA—AA—CO—NR3R4.

Abstract: This invention relates to the purification of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester by resolving a mixture of the alpha- and beta-isomers of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester using metal ions.

Abstract: This disclosure relates to the co-crystallization of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester with sugar in various ratios. The sugar co-crystallized sweetener is very soluble in water and has no dusting problems.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis.

Abstract: The present invention relates to conjugates of 3-carboxy-4,4′-dihydroxyphosphorylbutenoic acids with alkylating agents, derivatives are endowed with marked antitumor activity, especially against multiple myeloma. The present invention relates as well to a process for the preparation thereof and to pharmaceutical compositions containing them.

Abstract: Disclosed are compounds which inhibit &bgr;-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits &bgr;-amyloid peptide release and/or its synthesis.

Abstract: A process for preparing an agglomerate of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester and a carrier including the steps of: (a) providing a premix solution comprising N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester and a binding agent; (b) fluidizing a carrier; and (c) applying the premix solution of step (a) onto said fluidized carrier to form an agglomerate of said N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester and said carrier. Also the novel agglomerates prepared by the process of this invention.

Abstract: This invention is directed to a process for preparing a pseudotetrapeptide of formula I or a salt or prodrug thereof wherein is optionally nitrogen protected azaheterocyclyl; is a single or double bond; q is 1-5; B is alkyl, cycloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, aryl, aralkyl, alkylaryl, or alkylaralkyl; Q2 is H or a carboxylic acid protecting group; J is —H, alkyl, cycloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl; L is OR1, or NR1R2, where R1 and R2 are independently —H, alkyl, cycloalkyl, cycloalkylalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, aryl, aralkyl, alkylaryl or alkylaralkyl; and p is 1 or 2 which comprises the coupling of two dipeptides or psuedopeptides.

Abstract: Dipeptide sweeteners are disclosed that are salts of N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester represented by the formula wherein X− is selected from the group consisting of Cl−, HSO4−, H2PO3−, citrate, HCO3−, furmarate, malate, maleiate, tartarate, acetate, benzoate or gluconate. Also disclosed is a liquid low-calorie sweetener containing such salts.

Abstract: An amide compound of the formula (I): wherein R is amino and the like, A is alkylene and the like, X is O, S and the like, M is arylene and the like, R1, R2, R3 and R4 are H, hydroxy and the like, R5 is H, alkyl and the like, m is an integer of 0-6, R6 is an optionally substituted aryl and the like, and R7 is H, an optionally substituted alkyl and the like, a pharmaceutically acceptable acid addition salt thereof and a pharmaceutical containing same as an active ingredient. The amide compounds exhibit superior suppressive effects on cytokines directly or indirectly involved in inflammations, such as IL-8, IL-1, IL-6, TNF-&agr;, GM-CSF and the like, and are useful for the prophylaxis and treatment of rheumatic diseases, arthritis due to gout and the like.

Abstract: The present invention is directed to novel dipeptides represented by the general Formula I: ##STR1## where R.sub.1 -R.sub.2 and AA are defined herein. The present invention relates to the discovery that compounds having Formula I are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.

Abstract: Dipeptide sweeteners are disclosed that are metal complexes of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester represented by the formula ##STR1## wherein X.sup.p+ is selected from the group consisting of Al.sup.3+, Fe.sup.2+, Fe.sup.3+, Ca.sup.2+, Mg.sup.2+ and Zn.sup.2+ ; Y.sup.q- is selected from the group consisting of Cl.sup.-, SO.sub.4.sup.2-, PO.sub.4.sup.3- and CH.sub.3 COO.sup.- ; x is a number from 1 to 4 and pn=qm. Also disclosed is a liquid low-calorie sweetener containing such metal complexes.

Abstract: This invention relates to analogs of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.

Abstract: Dipeptide sweeteners are disclosed that are sweetener salts of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester represented by the formula ##STR1## wherein X.sup.m- is a conjugate base derived by deprotonation of an acidic sweetener, preferably saccharin, acesulfame, cyclamic acid and glycyrrhizic acid; and m=n. Also disclosed is a liquid low-calorie sweetener containing such basic salts.

Abstract: The invention includes selected novel optically active .alpha.-amino ketones which either are themselves useful or are intermediates for the preparation of known ketomethylene pseudopeptides useful as antibiotics, antibiotic enhancers, or enzyme inhibitors. Further, the present invention provides a method for dehydrogenation/asymmetrical hydrogenation to obtain essentially pure antipodes of ketomethylene pseudopeptides having two chiral centers.

Abstract: A process for the preparation of optically active phenylcyclohexylglycolate esters is described. The process utilizes carboxylic acid activation to couple (R)-- or (S)-cyclohexylphenylglycolic acid (CHPGA) with 4-N,N-diethylamino butynol or other propargyl alcohol derivatives. The preparation of the hydrochloride salt is also described. In addition, a resolution process employing tyrosine methyl ester enantiomers for preparing a single enantiomer of CHPGA from racemic CHPGA is disclosed.

Abstract: The present invention relates to oligopeptidic compounds having the general formula (I):K--[--A--].sub.z --[--B--].sub.w --L (I)The compounds having general formula (I) are antifungals for agricultural purposes.

Abstract: The invention provides novel PGF analogs. In particular, the present invention relates to compounds having a structure according to the following formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, X, and Z are as defined. This invention also includes optical isomers, diastereomers and enantiomers of the formula above, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof.The compounds of the present invention are useful for the treatment of a variety of diseases and conditions, such as bone disorders and glaucoma. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment for bone disorders and glaucoma using theses compounds or the compositions containing them.

Abstract: The present invention provides compounds having the Formula I ##STR1## The present invention also provides methods of treating atherosclerosis, coronary heart disease, and restenosis using the compounds of Formula I, and pharmaceutical compositions comprising the compounds of Formula I.

Abstract: A method for producing an optically active amino acid or derivative thereof having a high optical purity from an optically active amino acid comprising optical isomers or derivative thereof, which comprises any one of processes (A), (B), and (C), wherein the process (A) comprises the steps: (1) previously preparing an optically active amino acid or derivative thereof having an optical purity higher than a convergent value of a mutual solubility of the optical isomers and (2) crystallizing the optically active amino acid or the derivative thereof that exists in excess, said convergent value being a ratio of the desired optical isomer in the optical isomers dissolved in a mother liquor in which crystals of a racemate and an optically active compound coexist at equilibrium (the optical purity in a mother liquor). The processes (B) and (C) are described in the specification.

Abstract: A process for the synthesis of hydroxyethylene dipeptide isosteres from .alpha.-N,N-di(protected)amino(alkyl or substituted alkyl) methyl ketones that can be efficiently carried out on an industrial scale. The process proceeds with excellent diastereoselectivity and chemical efficiency, and can be used to prepare a wide variety of hydroxyethylene dipeptide isosteres for a variety of uses, including as HIV-1 protease inhibitors and renin inhibitors.

Abstract: Provided is a novel active oxygen-resisting agent which has an excellent active oxygen resistance and which exhibits a good solubility in an oil solvent. An active oxygen-resisting agent containing as an active ingredient an amino acid derivative represented by the following formula (I) ##STR1## wherein Ar represents a substituted or substituted 2-hydroxyphenyl group or a pyridyl group, said substitution being selected from the group consisting of a halogen atom, a C.sub.1-6 alkyl group, a hydroxyl group, a hydroxy C.sub.1-6 alkyl group, a nitro group, a C.sub.1-6 alkoxyl group or a carboxyl group, R.sup.1 represents a side chain of an amino acid, X represents --O-- or --NH--, R.sup.2 represents a C.sub.8-22 alkyl group, and n represents 0 or 1, or its salt.

Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitrites thereof, and are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, as anti-viral and anti-fungal agents or pro-drugs of such agents.

Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof, and are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, as anti-viral and anti-fungal agents or pro-drugs of such agents.

Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof.These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.5.

Abstract: A process for the preparation of disodium Z-L-aspartate from fumaric acid, in whicha) fumaric acid is reacted with ammonia in an inert diluent in the presence of aspartase or aspartase-producing microorganisms to give ammonium L-aspartate thenb) the ammonium L-aspartate-containing solution is treated with sodium hydroxide, forming, depending on the amount of sodium hydroxide used, the mono- or disodium L-aspartate or a mixture thereof, andc) the eliminated ammonia is returned to a fumaric acid suspension, which is used as starting solution for further enzymatic reactions, and thend) the residual mono and/or disodium L-aspartate-containing solution is reacted with benzyloxycarbonyl chloride at a pH of between 9 and 14, with the simultaneous addition of sodium hydroxide, to form disodium Z-L-aspartate.

Abstract: Compounds based on derivatives of .beta.-aminopropionic acid having the general formula (I): ##STR1## The compounds having general formula (I) have a high antifungal activity.

Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof.These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.5.

Abstract: A method is disclosed for preparing and purifying N-?N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl!-L-phenylalanine 1-methyl ester from aspartame and 3,3-dimethylbutyraldehyde by hydrogenation in an organic solvent solution followed by the formation of an aqueous/organic solvent solution having an organic solvent content of about 17% to about 30% by weight of the aqueous/organic solvent solution.

Abstract: The invention relates to a process for the preparation of N-protected-L-aspartyl-L-phenylalanine methyl ester by enzymatic coupling of an N-protected-L-aspartic acid and L- or DL-phenylalanine methyl ester in an aqueous solution with formation of a precipitate using a thermolysin-like protease enzyme, wherein a water-immiscible organic solvent is added to and blended with the reaction system during the formation of the precipitate in the course of the coupling reaction, which organic solvent has a relatively high affinity for the precipitate. The process is particularly suitable as a continuous process. The method results in lower enzyme deactivation during and after the enzymatic coupling reaction and in larger and thicker precipitated crystals.

Abstract: Diethylenetriaminepentaacetic acid monoamide derivatives, their complexes and complex salts, containing an element of atomic numbers 21-29, 31, 32, 39, 42-44, 49 or 57-83, pharmaceutical agents containing these compounds, their use as contrast media and process for their production.

Abstract: The invention relates to a process for the production of diethylenetriaminepentacarboxylic acid tetraesters of general formula I ##STR1## in which R.sup.1 and Z have different meanings.

Abstract: A method for preparing diphenol compounds, which method includes the steps of coupling a hydroxyphenyl carboxylic acid with a L-tyrosine ester in a water-miscible organic reaction solvent containing a carbodiimide capable of forming a water-soluble urea by-product, thereby forming a diphenol reaction product; and combining the reaction mixture with an amount of water effective to precipitate the diphenol as a water-immiscible organic phase, so that a water-immiscible organic phase is formed containing the diphenol reaction product. New diphenol monomers and polymers polymerized therefrom are also disclosed.

Abstract: Random block copolymers having the formula: ##STR1## wherein R.sub.1 is --CH.dbd.CH-- or (--CH.sub.2 --).sub.j, in which j is zero or an integer from one to eight; R.sub.2 is selected from hydrogen, straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and derivatives or biologically and pharmaceutically active compounds covalently bonded to said copolymer; each R.sub.3 is independently an alkylene group containing up to 4 carbon atoms; y is an integer between about 5 and about 3000; and f is the percent molar fraction of alkylene oxide in the copolymer and ranges between about 1 and about 99 mole percent. Implantable medical devices and drug delivery implants containing the random block copolymers are also disclosed, along with methods for drug delivery and for preventing the formation of adhesions between injured tissues employing the random block copolymers. Polyarylate random block copolymers are also described.

Abstract: A method for preparing diphenol compounds, which method includes the steps of coupling a hydroxyphenyl carboxylic acid with a L-tyrosine ester in a water-miscible organic reaction solvent containing a carbodiimide capable of forming a water-solvent urea by-product, thereby forming a diphenol reaction product; and combining the reaction mixture with an amount of water effective to precipitate the diphenol as a water-immiscible organic phase, so that a water-immiscible organic phase is formed containing the diphenol reaction product. New diphenol monomers and polymers polymerized therefrom are also disclosed.