56 results about "D tryptophan" patented technology

The invention discloses a preparation method of tadalafil. The concrete preparation method is used for successfully synthesizing tadalafil by taking L-tryptophan methyl ester hydrochloride as an initial raw material and utilizing the characteristics that an ortho-position of an ester group has the chiral inversion property under an alkaline condition, the reaction between ester group and Pictet-Spengler is reversible reaction, and the ester group is easily converted into a cis-form product with relatively small solubility, therefore, the preparation method is a brand new technology. The price of L-tryptophan methyl ester hydrochloride is only less than 1 / 5 of that of D-tryptophan methyl ester hydrochloride, so that the cost of the overall route is greatly lower than that of the prior art, and then the preparation method is suitable for industrial production.

The invention discloses a feed sweetener which is prepared by mixing the following components in parts by weight: 25-70 parts of soluble saccharin, 5-70 parts of maltodextrin, 1-10 parts of sweet taste intensifier, 0.01-0.1 part of ethyl maltol and 0.01-0.1 part of ethyl vanillin, wherein the sweet taste intensifier is one of Acesulfame-K, sucralose, alitame and D-tryptophan or a mixture formed by mixing Acesulfame-K, sucralose, alitame and D-tryptophan according to any ratio. The sweetener enables animals to truly and effectively taste all the components, thereby increasing the feed intakes of the animals and improving the production performance of the animals. The sweetness of the sweetener is 150-500 times higher than that of sucrose, and the sweetener has sucrose-like fragrance and mouth feel, thereby reducing the additive amount of the sweetener in the feed and lowering the culture cost. The sweet taste intensifier in the invention has good stability, and the decomposition temperature is higher than the preparation temperature, so that the sweet taste intensifier can not be decomposed in the sweetener preparation process and the feed granulating process, thereby ensuring that the sweet taste is true and effective.

The invention belongs to the field of preparation of chemical raw medicaments, and more in particular relates to an improved preparation method for a phosphodiesterase 5 inhibitor tadalafil. A specific synthesis route is shown in the specification. The method comprises the following steps of performing Pictet-Spengler cyclization reaction and chloroacetyl chloride acylation on starting reactants (D-tryptophan methyl ester hydrochloride and piperonal) to obtain an intermediate product, directly performing subsequent reaction on the intermediate product without purification, preparing an intermediate 1-(1,3-benzodioxol-5-yl)-2-(chloracetyl)-2,3,4,9-tetrahydro-1H-pyridino-[3,4,-B]indol-3-thiophenate methyl by using a one-pot reaction method, performing column chromatography purification to obtain a single cis-isomer, and finally reacting the single cis-isomer with methylamine hydrochloride in the presence of an inorganic base to obtain the tadalafil.

A thin film composition for oral administration that adheres to and dissolves in a mouth of a user, wherein the thin film is a single layered water-soluble solid comprising at least one D-amino acid contained in a plurality of hydrophobic carriers dispersed throughout the thin film. The hydrophobic carriers comprise oil and the composition further comprises a phospholipid, an emulsifier, and a water soluble polymer. The preferred D-amino acids are D-leucine, D-tryptophan, D-methionine, and D-tyrosine. A method of reducing dental plaque in a subject entails placing the thin film composition contemplated herein into a mouth of the subject.

The invention discloses a liquid synthetic method of pasireotide pentapeptide intermediate, i.e., a preparation method of H-Phg-D-Trp-Lys(Boc)-Tyr(Bzl)-Phe-OR. By using the liquid linker peptide synthetic method, reaction is easy to detect, the cost is lower than that of a solid synthetic method, and the method is more suitable for large-scale industrial production. The liquid synthetic method includes the main synthetic steps of linking carbobenzoxy-protected D-tryptophan and 9-fluorenylmethoxycarbonyl-protected phenylglycine one by one to Alpha-N terminals of lysine to obtain a tripeptide fragment in 3+2 mode through BSA protected lysine and N-hydroxysuccinimide ester method; condensing ester-protected phenylalanine and t-butyloxycarboryl-protected O-benzyl-tyrosine to obtain a dipeptide fragment through N-hydroxysuccinimide ester method; condensing the tripeptide and dipeptide through TBTU method to obtain the target product, pasireotide pentapeptide intermediate.

The invention discloses a preparation method of tadalafil, starting material D-Tryptophan methyl ester hydrochloride is reacted with oxalyl chloride to obtain an intermediate III, and the final product tadalafil (I) is obtained through cyclization, Grignard reaction, asymmetric reduction, substitution and condensation reaction. The use of national control chemical piperonal is avoided, an intermediate VI can be highly-selectively obtained by the asymmetric reduction, and the method has the advantages of simple postprocessing, short synthesis steps and high product total yield, and is suitable for industrialized production.

The present invention relates to the field of targeting drug delivery agents of polypeptide drugs, and particularly to a D-glutamyl-D-tryptophan sodium colon targeting delivery agent and a preparation method thereof. The colon targeting delivery agent comprises a tablet core, a pH value control layer, and a flora trigger layer. With the colon targeting drug delivery agent, the purpose of colon targeting drug delivery can be achieved, bioavailability of the D-glutamyl-D-tryptophan sodium is improved, and good mixing hardness and low toxicity of the agent of the present invention are provided compared with injection administration and nasal administration.

The invention provides a preparing method of a beta-cyclodextrin immobilized cellulose membrane used for tryptophan chiral separation. According to the preparing method, the cellulose membrane is selected to be used as a base membrane material due to the advantages that the molecular structure per se of the cellulose membrane has multiple active hydroxyls capable of being used for modification, in addition, the price is low, and the acquisition is easy. Beta-cyclodextrin is chemically bonded on the cellulose membrane with the bore diameter of 0.22[mu]m, and chiral separation membranes are prepared. Racemic tryptophan is used as a separation object; in addition, separation effects are expressed; after the multilayer filtering, the modified filter membrane almost achieves the complete separation on DL-tryptophan; and a D-tryptophan solution is obtained. The separation performance stability RSD of the chiral membranes in 12h reaches 3.4 percent, and the stability is good. The preparing method can be widely applied to the field of chemical medicine separation.

The invention relates to an improved method of preparing a compound (II). The improved method comprises the following steps: (the formula is shown in the description) 1, mixing D-tryptophan, methanol and toluene, adding thionyl chloride dropwise, and then carrying out reaction at the temperature of 70-85 DEG C to obtain D-tryptophan ester hydrochloride, wherein the structure is shown in a formula (III):(the formula is shown in the specification); and 2, mixing the D-tryptophan ester hydrochloride, a compound (IV) and a nitrile solvent, uniformly stirring, then raising the temperature to 75-85 DEG C, and carrying out reaction, (the formula is shown in the description). The improved preparation method of the compound shown by the D-tryptophan ester hydrochloride (II) has the following beneficial effects: 1, the dosage of the thionyl chloride in the first step is greatly reduced, so that the risk and the corrosion of the reaction are lowered, the post-processing is simple, and the yield is above 90 percent; 2, in the second step, the nitrile solvent is adopted to improve the stereoselectivity, and the enantiomer extra amount (ee %) is above 99 percent.

The invention discloses preparation of a graphene-based carboxymethylcellulose nanocrystalline composite material. The preparation of the graphene-based carboxymethylcellulose nanocrystalline composite material comprises mixing graphene oxide dispersion liquid with sodium carboxymethylcellulose aqueous solution, and meanwhile adding in ethanediamine and a cross-linking agent of N-N-hydroxysuccinimide for continuous reaction at 48-55 DEG C for 50-53 h; then, adding in hydrazine hydrate to reduce superfluous oxygen-containing functional groups and carbon-oxygen double bonds on graphene oxide, and then performing suction filtration, washing and drying to obtain the graphene-based carboxymethylcellulose nanocrystalline composite material. Through a dripping method, the graphene-based carboxymethylcellulose nanocrystalline composite material is modified on a glassy carbon electrode to form an electrochemical chiral sensing interface, and the electrochemical chiral sensing interface is arranged inside L-tryptophan or D-tryptophan solution separately and scanned through differential pulse voltammetry. Due to the fact that the steric hindrances as well as the peak currents when L-tryptophan and D-tryptophan interact with the modified electrodes are different, the graphene-based carboxymethylcellulose nanocrystalline composite material can help rapidly and sensitively achieve recognition of tryptophan isomers.

The invention discloses a preparation method of dodecanoyl-beta cyclodextrin and a preparation method of a polysulfone membrane for tryptophan chiral resolution, and belongs to the technical field of chiral resolution. Amphipathic dodecanoyl-beta cyclodextrin is prepared from beta cyclodextrin and lauroyl chloride by adopting a one-step synthesis method to serve as a chiral selector, and a polysulfone material with high mechanical strength, compressive tightness, chemical stability, heat resistance, wide pH application range, low price and simple preparation method is used as basic membrane material to prepare the polysulfone membrane for resolution. Racemic tryptophan is used as a resolution object, the concentration and a concentration ratio of D-tryptophan and L-tryptophan are monitored by high performance liquid chromatography, and the prepared amphipathic chiral membrane has a stable resolution effect within 12h and good performance.

The invention relates to a preparation method of a selective and reversible inhibitor tadalafil of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase 5 (PDE5). The method comprises the following steps: carrying out an esterification reaction on D-tryptophan as an initial raw material and methanol under catalysis of sulfuric acid to generate D-tryptophan methyl ester (an intermediate1); carrying out a Pictet-Spengler (P-S) reaction on the D-tryptophan methyl ester and heliotropin to prepare (1R,3R)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester hydrochloride (an intermediate 2); carrying out an amidation reaction on the (1R,3R)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester hydrochloride and chloroacetyl chloride to prepare (1R,3R)-1-(1,3-benzodioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester (an intermediate 3); andfinally carrying out a cyclization reaction on the (1R,3R)-1-(1,3-benzodioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester and a methylamine alcohol solution to obtain the tadalafil. The method provided by the invention has the advantages of easily available raw materials, simple operation, greenness, environmental protection and low costs, andis suitable for industrial production.

The invention relates to an improvement on a synthesis method of a tetrahydro-beta-carboline compound (II). The method comprises reacting D-tryptophan methyl ester hydrochloride and piperonal at 50 DEG C-150 DEG C in a certain solvent to obtain hydrochloride of a structural formula (II) compound, wherein the solvent can be nitroethane, dioxane, methylbenzene, dimethylbenzene, benzene or nitrobenzene. The yield and purity of products prepared by the method are greatly improved, and the method is especially suitable for industrial production.

The invention discloses a cis-tetrahydrocarboline intermediate and a synthesis method thereof, and application of the cis-tetrahydrocarboline intermediate in preparing tadalafil. D-tryptophan methyl ester hydrochloride and 3,4-dihydroxybenzaldehyde are used as raw materials to prepare the cis-tetrahydrocarboline intermediate, so that the raw materials are accessible, thereby overcoming the technical defects when the police-controlled precursor chemical heliotropin is used as the raw material in the prior art. The preparation method does not need any catalyst, and can be used for directly preparing the cis-tetrahydrocarboline intermediate by using lower alcohols, nitriles or nitroparaffins as a solvent; and after the reaction finishes, simple cooling and filtration are performed to obtain the product, wherein the mole yield is 90-97%. The cis-tetrahydrocarboline intermediate can be used for preparing tadalafil; and the synthesis method is simple and easy to implement, has the advantages of stable technique and high yield, and is suitable for industrial large-scale production. The structural formula of the cis-tetrahydrocarboline intermediate is disclosed as (I).

The invention discloses a preparation method of tadalafil. The method employs D-tryptophan as a starting material to synthesize tadalafil. The preparation method of tadalafil provided by the invention can effectively prepare tadalafil, and has high synthesis efficiency; and the prepared tadalafil has high purity. In addition, the preparation method has the advantages of easily available starting raw materials, simple process operation, mild reaction conditions, no special reaction equipment and no inseparable compound in the preparation process, thus the method is more suitable for large-scale industrialized production of tadalafil.

The invention relates to a preparation method of a D-tryptophan lower alcohol ester hydrochloride with high optical purity. The preparation method comprises the steps of: (1) reacting D-tryptophan and sulfoacid lower alcohol ester in a solvent at the temperature of 25-100 DEG C to produce D-tryptophan lower alcohol ester sulfonate; (2) dissolving the D-tryptophan lower alcohol ester sulfonate in water, adjusting the pH to alkaline with alkali so as to invert the D-tryptophan lower alcohol ester sulfonate into D-tryptophan low alcohol ester, performing extraction with an organic solvent after reaction is finished, and adding a drying agent for dehydration to obtain an extract liquor containing D-tryptophan low alcohol ester; and (3) introducing dry hydrogen chloride gas into the extract liquor containing D-tryptophan low alcohol ester to react, thereby producing the D-tryptophan lower alcohol ester hydrochloride. The preparation method is stable during production and avoids tryptophan decomposition and other side reactions, so that both the yield and the optical purity of the D-tryptophan lower alcohol ester hydrochloride are enhanced.

The present invention relates to the field of targeting drug delivery agents of polypeptide drugs, and particularly to a D-glutamyl-D-tryptophan sodium colon targeting delivery agent and a preparation method thereof. The colon targeting delivery agent comprises a tablet core, a pH value control layer, and a flora trigger layer. With the colon targeting drug delivery agent, the purpose of colon targeting drug delivery can be achieved, bioavailability of the D-glutamyl-D-tryptophan sodium is improved, and good mixing hardness and low toxicity of the agent of the present invention are provided compared with injection administration and nasal administration.

The invention discloses a new process for producing D-tryptophan by a chemical method and an enzymic method. The process is characterized in that the process comprises the following steps: racemization, resolution, refining of N-acetyl-DL-tryptophan, hydrolysis, refining of D-tryptophan hydrochloride, decomplexation, and treatment of mother liquor. The process is characterized in that the production process with combination of the chemical method and the enzymic method comprises racemization, resolution, refining and hydrolysis of L-tryptophan and refining of D-tryptophan hydrochloride, and D-tryptophan is obtained, and production efficiency is improved; mother liquor generated in the synthesis process is condensed, cyclic utilization is carried out, discharge capacity of the mother liquoris reduced, yield of the product is improved, and at the same time by-products are decomplexed and cyclic utilization is carried out, and waste of resource is reduced; in the synthesis process, wateris used as a solvent, in order to solve the defect that organic matters are used as solvents in the conventional methods with safety and environmental protection; extra racemase and resolving agentsare not needed to add, the process route is short, and production process is simple.

The invention discloses a compound acyl intermediate as well as a synthetic method and application thereof in preparing tadalafil. The synthetic method comprises the following steps: preparing (1R, 3R)-methyl-1-(3,4-dihydroxyphenyl)-2,3,4,9-tetrahydro-1H-pyridino[3,4-b]indol-3-carboxylic acid (compound I) by taking D-tryptophan methyl ester hydrochloride and 3,4-dihydroxy benzaldehyde as raw materials, and allowing the compound I to have chloroacetylation with chloroacetyl chloride to generate the compound acyl intermediate. By adopting the method, raw materials are easy to get, so that the technical weakness caused by using the poisonable chemical heliotropin controlled by the public security department in the prior art as a raw material is overcome. The preparation process requires no catalyst, and the yield is high. The obtained compound acyl intermediate can be used for preparing the tadalafil, and is simple and easy, stable in process, low in cost, and suitable for industrialized mass production. The structural formula of the compound acyl intermediate is shown as formula (II): (see the description) (II).

The invention provides a D-amino acid antibacterial peptide PRW4-d and a preparation method and an application thereof. A sequence of the peptide is as shown in a sequence table SEQ ID No.1. The preparation method comprises the following steps: by taking antibacterial peptide PRW4 as a template, replacing tryptophan in the antibacterial peptide PRW4 by using an amino D-tryptophan with different spiral tendentiousness; replacing all lysine in the PRW4 by arginine; and obtaining peptide resin through a polypeptide synthesizer by virtue of a solid phase chemical synthesizing method and performing TFA cutting on the obtained peptide resin to obtain the poly peptide PRW4-d. The polypeptide PRW4-d has an obvious inhibiting effect on various cultures such as escherichia coli, salmonella typhimurium, staphylococcus aureus and bacillus subtilis, is very low in hemolytic activity, and shows relatively high cell selectivity. In a word, the PRW4-d is the antibacterial peptide which is relatively high in application value.

The invention discloses engineering bacteria for producing D-tryptophan and a construction method and a purpose of producing D-tryptophan. The construction method comprises the following steps: transferring an acylated amino acid racemase mutant gene and a N-acetyl-D-amino acid acyl hydrolase mutant gene in escherichia coli, and constructing the engineering bacteria for producing D-tryptophan. Theconstruction method optimizes the N-acetyl-D-amino acid acyl hydrolase mutant gene and the acylated amino acid racemase mutant gene, the acyl hydrolysis activity of the N-acetyl-D-tryptophan by the N-acetyl-D-amino acid acyl hydrolase and the racemization activity of the N-acetyl-L tryptophan by the acylated amino acid racemase are increased, and the output and the product quality of the D-tryptophan are increased. Two types of enzymes can be expressed by the same engineering bacterial strain, the fermentation cost is saved, and the production technology is simplified.

The invention discloses a method for detecting the concentration of D-tryptophan in a solution. D-tryptophan in the solution to be detected is detected through differential pulse voltammetry with a three-electrode system, and the concentration of D-tryptophan in the solution to be detected is obtained according to a linear equation of D-tryptophan, wherein working electrodes in the three-electrode system are modified glassy carbon electrodes obtained by modifying glassy carbon electrodes with nitrogen-doped carbon dots and beta-cyclodetrin. By means of the method, the concentration of D-tryptophan can be rapidly detected; besides, sensitivity and accuracy are high.

The invention discloses a preparation method of tadalafil. The concrete preparation method is used for successfully synthesizing tadalafil by taking L-tryptophan methyl ester hydrochloride as an initial raw material and utilizing the characteristics that an ortho-position of an ester group has the chiral inversion property under an alkaline condition, the reaction between ester group and Pictet-Spengler is reversible reaction, and the ester group is easily converted into a cis-form product with relatively small solubility, therefore, the preparation method is a brand new technology. The price of L-tryptophan methyl ester hydrochloride is only less than 1 / 5 of that of D-tryptophan methyl ester hydrochloride, so that the cost of the overall route is greatly lower than that of the prior art, and then the preparation method is suitable for industrial production.

The invention belongs to the technical field of medicinal chemistry, and discloses a preparation method and an application of a tadalafil cis-intermediate, which comprises the following steps: by using D-tryptophan methyl ester hydrochloride as an initial raw material, mixing the raw material with heliotropin in a glycol ether solution to obtain a cis-intermediate, wherein the ratio of the D-tryptophan methyl ester hydrochloride to the heliotropin is 1:(1.1-1.5), and the ratio of the D-tryptophan methyl ester hydrochloride to the glycol ether is 1g to 4ml; the glycol ether is one or a mixtureof more of ethylene glycol monomethyl ether, propylene glycol monomethyl ether, butanediol monomethyl ether, propylene glycol dimethyl ether, ethylene glycol dimethyl ether and butanediol dimethyl ether. The method disclosed by the invention is short in synthesis time, simple to operate and high in yield, and the prepared cis-intermediate is high in purity. The intermediate does not need to be refined and can be directly used for preparing tadalafil.

The invention belongs to the field of crop disease control, and discloses an application of D-amino acids in inhibition for the biofilms of banana bacterial Erwinia carotovora and a culture medium thereof. The D-amino acids screened in the application disclosed by the invention are capable of remarkably and effectively inhibiting the growths of the bacterial biofilms of banana bacterial Erwinia carotovora. According to the application disclosed by the invention, four D-amino acids capable of remarkably inhibiting the growths of the bacterial biofilms of banana bacterial Erwinia carotovora, that is, D-tyrosine, D-valine, D-methionine and D-tryptophan are obtained by screening; and the lowest inhibition concentrations of the four D-amino acids are obtained. The invention further provides a mixing formula of the four D-amino acids, thus the use concentrations of the various D-amino acids are greatly reduced. The invention further provides a D-amino acid culture medium used for the application. On the basis of the contents of the invention, new method and thought can be provided for the development of new control technologies for bacterial Erwinia carotovora; the use effects of control methods such as chemical pesticides and biological pesticides are improved in combination with the use of the D-amino acids.

The invention discloses a novel synthetic method of a beta-tetrahydrocarboline compound by using pentamethyleneamine as a raw material, belonging to the synthesis field of medical intermediates. The invention aims to provide a novel method for preparing the beta-tetrahydrocarboline compound by using pentamethyleneamine as the raw material through formylation reaction in a two-steps cascade reaction manner, wherein the first step of reaction is used for preparing a mixture containing heliotropin and pentamethyleneamine, and the mixture is simply treated but not separated and then directly carries out second step of P-S reaction with D-tryptophan methyl ester or a salt of D-tryptophan methyl ester for cascade-preparing the beta-tetrahydrocarboline compound. Compared with the traditional synthetic method, the synthetic method is a cascade reaction, thereby avoiding purchasing and storing heliotropin which is a precursor chemical product and omitting a complex purification step. The novel synthetic method has the advantages of reducing the cost, saving expenses, having low requirements on production equipment and environment conditions, and achieving high yield and is suitable for industrial production.

The invention discloses a D-tryptophan methyl ester hydrochloride drying device based on a lifting and discharging technology. A box body is of a cylinder structure with an opening in the top end, a supporting table is arranged on the edge of the bottom wall of the inner cavity of the box body, and a guide rail is arranged at the top end of the supporting table; a base is arranged at the top end of the guide rail, the guide rail is rotationally connected to the base, an electric telescopic device is arranged in the center of the top end surface of the base, a plurality of supporting rods are uniformly arranged on the outer circle surface of a telescopic rod on the electric telescopic device, and base plates are arranged on one sides, away from the telescopic rod, of the top end surfaces ofthe supporting rods; and a clamping cavity is formed in the top end of each base plate, and a placing plate is arranged in each clamping cavity. According to the device, the telescopic rod is jackedup through the electric telescopic device, so that all the base plates are supported to be separated from the box body, and loading and unloading of the placing plates are completed; a worker finishesloading and unloading above the box body, the position is close to the box body, and the safety of the worker can be protected to the largest extent; and the acid gas in the box body can be timely discharged through an exhaust bucket, the residual of the polluted gas in the box body can be reduced, and the safety of the worker can be guaranteed.

The present invention relates to pharmaceutically acceptable crystalline and amorphous salts of D-isoglutamyl-D-tryptophan as well as processes for their manufacture, pharmaceutical compositions comprising them, and their uses in the preparation of pharmaceutical compositions for the treatment of various conditions and / or diseases. In particular, the present invention relates to D-isoglutamyl-D-tryptophan potassium salt (1:1), D-isoglutamyl-D-tryptophan lithium salt (1:1), D-isoglutamyl-D-tryptophan calcium salt (2:1), D-isoglutamyl-D-tryptophan magnesium salt (2:1), and D-isoglutamyl-D-tryptophan organic ammonium salts (1:1).

The invention discloses a method for synthesizing tadalafil. Tadalafil is synthesized from D-tryptophan and a compound of formula 1. The method for preparing tadalafil of the invention can effectivelyprepare tadalafil. In addition, the starting material piperonyl dimethyl acetal of the preparation method is easy to obtain as a non-controlled material, the procurement and management are not restricted, the use of the controlled material piperonyl is effectively avoided, the management and procurement are convenient, the process steps are short, the production cost is greatly reduced, and the preparation method is more suitable for large-scale and industrial production of tadalafil.