53 results about "D-Phenylalanine" patented technology

A peptide of the formula IX-A-D-Trp-Ywherein X is hydrogen, glycine, alanine, leucine, isoleucine, valine, N-valine, proline, tyrosine, phenylalanine, tryptophan, D-alanine, D-leucine, D-isoleucine, D-valine, D-N-valine, D-proline, D-tyrosine, D-phenylalanine, D-tryptophan, gamma -aminobutyric acid or xi -aminocaproic acid; A is D-gluptamic acid or D-y-glutamic acid; and Y is glycine, alanine, leucine, isoleucine, valine, N-valine, proline, tyrosine, phenylalanine, tryptophan, D-alanine, D-leucine, D-isoleucine, D-valine, D-N-valine, D-proline, D-tyrosine, D-phenylalanine, D-tryptophn, gamma -aminobutyric acid, xi -aminocaproic acid, hydroxyl, or an amide group.

Provided is a process for preparation of an intermediate in the synthesis of nateglinide. Trans-4-isopropylcyclohexane acid chloride is formed by reacting 4-isopropylcyclohexanecarboxyl acid with thionyl chloride in the presence of an effective amount of an organic amide.

Also provided are processes for preparation of nateglinide by acylation of a suitable salt of D-phenylalanine with trans-4-isopropylcyclohexane acid chloride in both a single and a two phase system, and in water free of a co-solvent.

The method for preparing D-phenylalanine by using DL-phenylalanine includes the following steps: firstly, mixing DL-phenylalanine and D-tartaric acid according to the mole ratio of 1:1.5-1.5:1 and dissolving them in organic solvent, adding 1.0-5.0% of aromatic alolehyde catalyst and making reaction for 6-8 hr. at 70-90 deg.C, cooling by using ice water bath, filtering, using anhydrous ethyl etherto wash and drying to obtain D-tartaric acid: D-phenylalanine salt, then dissolving the above-mentioned product in solvent, adding ammonization agent to make ammonization while stirring, after 1 hr. cooling to 5 deg.C-10 deg.C, filtering and washing with solvent so as to obtain the invented D-phenylalanine.

The invention belongs to the field of organic chemical synthesis, and discloses cyclic pentapeptide with a novel structure, as well as a synthetic method and application thereof. The cyclic pentapeptide with the novel structure is cyclo-(N-Me-D-Phe-D-Leu-N-Me-D-Leu-D-Leu-L-Leu), the molecular formula is C35H57N5O5, and the structural formula is shown in the description. The cyclic pentapeptide adopts D-Leu, L-Leu, D-Phe and D-Leu benzyl ester tosilate as raw materials, a tripeptide midbody and a dipeptide midbody are respectively prepared through a proper technology, and a cyclization locus is selected at the amido linkage position adjacent to D and L configurations, so that the cyclization efficiency is effectively increased. The cyclic pentapeptide has the advantages of simple synthetic process, low raw material cost, mild reaction conditions, high purity and easy industrial production, and can fully meet the requirements of medical experiments and clinical application.

The invention relates to a method for producing D-phenylalanine by using L-phenylalanine as a raw material. The method comprises the following steps: preparing the L-phenylalanine into 0.3-0.4kg/L aqueous solution; adjusting the pH value to 8-13 with sodium hydroxide solution; dropping acetic anhydride for acylating; controlling the reaction temperature below 40DEG C until no color displays in a ninhydrin reaction; adjusting the pH value of the acylated acetyl-L-phenylalanine to 4-6 by using hydrochloric acid; when the temperature is raised to 60-90DEG C, dropping the anhydride for racemizing; when a rotation value of a racemic liquid is less than or equal to 0.1, adjusting the pH value of the racemic liquid to 1-4 with the hydrochloric acid and cooling and crystallizing to obtain an acetyl-DL-phenylalanine crystal; preparing the obtained acetyl-DL-phenylalanine crystal into 0.04kg/L resolution liquid, adjusting the pH value to 7.8-8.2, adding 15mg/L enzyme D, preserving the heat of 40DEG C for 24 hours and stopping resolution; and extracting the resolution liquid through cation exchange resin to obtain the D-phenylalanine. The method disclosed by the invention has the advantages of simple process flow, capability of obtain high-purity products and low cost.

The invention discloses a method for preparing D-phenylalanine through dynamic kinetic resolution. The method comprises the following steps of: reacting L-phenylalanine serving as raw materials with hydrochloric acid to generate L-phenylalanine hydrochloride; racemizing and resolving under the action of a solvent and a racemization catalyst by taking the L-phenylalanine hydrochloride as a substrate and dibenzoyl tartaric acid (L-DBTA) as a resolving agent to obtain D-phenylalanine.L-DBTA disalt; and finally performing triethylamine resolution to prepare the target product D-phenylalanine. Compared with the prior art, the method directly takes the L-phenylalanine as the resolving substrate, mild alcohol as the solvent and an aldehyde pyridine compound as the racemization catalyst, racemizes and resolves the L-phenylalanine into the D-phenylalanine.L-DBTA disalt, has a theoretical conversion rate of about 100 percent, greatly improves the resolution yield, reduces the operating cost, ensures stable product quality and is suitable for industrial production.

There is provided methods for producing nateglinide crystals, which comprises the steps of adding an acid(s) to a reaction mixture containing nateglinide to make it acidic, the reaction mixture being obtained by reacting trans-4-isopropylcyclohexylcarbonyl chloride with D-phenylalanine in a mixed solvent of ketone solvent and water in the presence of an alkali; and then adjusting the temperature of the mixture to 58° C. to 72° C. and the concentration of ketone solvent to more than 8 wt % and less than 22 wt % to conduct precipitation of nateglinide crystals. This producing method is the industrially beneficial methods for crystallization of nateglinide.

Compounds that modulate natural β amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a β amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a β amyloid peptide, preferably a retro-inverso isomer of Aβ_17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

The present invention relates to a process for the preparation of nateglinide, preferably in B-form, substantially free from the H-form, comprising three steps starting from D-phenylalanine methyl ester or a salt thereof.

The invention relates to a chemical synthesis method for preparing chiral D-phenylalanine. The chemical synthesis method comprises the following reaction steps: (a) carrying out hydrogenation reduction on acetamidocinnamic acid and derivatives thereof (I) in the presence of a chiral catalyst to obtain acetamido-D-phenylalanine (II), and (b) carrying out hydrolysis reaction on the acetamido-D-phenylalanine to remove acetyl, thus obtaining D-phenylalanine (III).

The invention relates to a biological bioactive peptide, and the molecular formula thereof is C42H67N7O10. When in preparation, tetrapeptide fragment N-(t-butoxycarbonyl)-L-isoleucine-N-methyl-D-phenylalanine-L-proline methyl ester is firstly prepared (t-butoxycarbonyl: BOC); then N-(9-fluorenylmethyloxycarbonyl)-N-methyl-glutamine is prepared (fluorenylmethyloxycarbonyl: Fmoc); then dipeptide fragment L-2-hydroxyl-3-methyl phocenic acid-O-benzyl salicylate-leucine is prepared; finally, the tetrapeptide fragment is detached from protecting groups and goes through condensation with N-(9-Fmoc)-N-methyl-glutamine, thus obtaining pentapeptide fragment N-(9-Fmoc)-N-methyl-glutamine-L-isoleucine-N-methyl-D-phenylalanine-L-proline methyl ester which goes through condensation after the dipeptide fragment and the pentapeptide fragment are detached from protecting groups. The biological bioactive peptide can provide sufficient raw materials and effective synthetic routes for the research of anti-tumor medicines and has a simple and convenient preparation method and easily controllable conditions.

The invention discloses a method for synthesizing an AHU377 calcium salt. The method comprises the following steps: reacting 4-bromo-D-phenylalanine with thionyl chloride, reacting obtained methyl 4-bromo-D-phenylalaninate hydrochloride with BOC acid anhydride, reacting the obtained reaction product with phenylmagnesium bromide to obtain N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methylester, reacting the N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methyl ester with sodium borohydride, reacting the obtained reaction product with ethyl 2-(triphenylphosphoranylidene)propionate to obtain ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoate, reacting the ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoatewith lithium hydroxide, performing catalytic hydrogenation, reacting the obtained catalytic hydrogenation product with thionyl chloride to obtain ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, and stirring and reacting the ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, calcium chloride and succinic anhydride to obtain the target product.The method has the advantages of simple steps, mild reaction conditions, high purity and high yield.

The invention discloses a preparation method for chiral L-alanyl-phenylalanine, belonging to the technical field of synthesis of organic matters. The method comprises the following steps: subjecting L-phenylalanine, D-phenylalanine or DL-phenylalanine and D-2-chloropropionyl chloride to condensation so as to obtain 2-chloropropionyl-phenylalanine with a corresponding configuration; carrying out ammoniation on 2-chloropropionyl-phenylalanine so as to obtain a crude L-alanyl-phenylalanine product with a corresponding configuration; and purifying the crude product so as to obtain finished L-alanyl-L-phenylalanine, L-alanyl-D-phenylalanine or L-alanyl-DL-phenylalanine. The method provided by the invention is low in raw material consumption and high in yield; and prepared chiral L-alanyl-phenylalanine has high quality and can meet requirements of industrial production.

The invention discloses a method for preparing D-phenylalanine through asymmetric transformation of L-phenylalanine, and belongs to the technical field of chirality organic compounds. The method comprises steps: dissolving the L-phenylalanine and aldehyde catalysts in organic acid, adding D-tartaric acid, performing a reaction for 5-10 hours at the temperature of 60-90 DEG C, performing cooling and filtration, and washing a solid with an organic solvent so as to obtain D-tartaric acid .D-phenylalanine salt; and adding the obtained D-tartaric acid .D-phenylalanine salt into alkali liquid in batches, performing dissociation, performing a stirring reaction for 1-2 hours, and performing filtration, washing and drying so as to obtain the D-phenylalanine. The method disclosed by the invention solves the problems of poor stability, low resolution efficiency, poor product quality, high production cost and the like existing in the technology of preparing the D-phenylalanine through the L-phenylalanine. The method disclosed by the invention has the advantages of being high in yield, low in production cost, simple to operate, easy in industrialization and the like.

The invention relates to a synthesis method of a nateglinide, in particular to the synthesis of the nateglinide by a one-pot method. Original material D-phenylalanine is used as raw material in the method, D-phenylalanine esterified substance (II) is obtained through esterification, a compound (IV) is obtained through acylation of isopropylcyclohexanecarboxylic acid (III), and then the compound (IV) is ester hydrolyzed so as to obtain the nateglinide. The technique of the method has simple technique process and easy and convenient post-treatment; meanwhile, the method has the advantages of strong operability, being easy to be industrialized and cost saving.

The invention discloses a method and a system for producing D-phenylalanine. The method comprises the following steps: adding water to dissolve a D-phenylalanine and D-tartaric acid double salt, adding ammonia water to adjust the pH value to the isoelectric point of D-phenylalanine, adding the obtained solution into the raw water chamber of an electrodialysis device, introducing the aqueous solution of D-phenylalanine in the raw water chamber into a first concentrating crystallization kettle when the electric conductivity is about zero, performing concentrating crystallization, centrifuging and drying to obtain D-phenylalanine, introducing D-tartrate ions in a cathode concentrating chamber into a second concentrating crystallization kettle, performing concentrating crystallization and centrifuging to obtain D-tartaric acid, and returning the obtained D-tartaric acid into a second reaction vessel for reuse. Existing methods and systems are improved, and the electrodialysis device is used to separate the obtained double salt in order to obtain the D-phenylalanine, so the method and the system have the advantages of simplicity and easiness in operation, time saving, high yield reaching 85-90%, no use of methanol or triethylamine, low cost and environmental protection.

Compounds that modulate natural β amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a β amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a β amyloid peptide, preferably a retro-inverso isomer of Aβ_17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an acetate group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

Compositions containing one or more tyrocidines, tryptocidines, phenycidines and/or gramicidin S, or derivatives and analogues thereof, are described for controlling antimicrobial growth on plants, plant material or plant growth media, and methods for controlling or preventing the growth of microbial pathogens, and in particular fungal pathogens, on plants, plant parts and plant material are described herein. The active agents used to control these pathogens are tyrocidines, tryptocidines, phenycidines and/or gramicidin S, or derivatives, analogues or modifications thereof. The tyrocidines, tryptocidines, phenycidines and/or gramicidin S are cyclic decapeptides having the general amino acid sequence cyclo(valine-Xrleucine-D-phenylalanine-proline-X₂-X₃-X₄-X₅-X₆) (SEQ ID NO: 1) or a derivative or analogue thereof, wherein X₁ is ornithine or lysine, X₂ is valine, leucine, isoleucine, phenylalanine, tryptophan or tyrosine; X₃ is the D-isomer of valine, leucine, isoleucine, phenylalanine, tryptophan, tyrosine, ornithine, or lysine; X₄ is asparagine, glutamine or leucine; X₅ is glutamine, the D-isomer of valine, leucine, or isoleucine; and X6 is tyrosine, phenylalanine, tryptophan or proline.