67 results about "Prolinol" patented technology

The present invention discloses methods for producing synthetic surfaces that mimic collagen coated surfaces for cell culture comprising: providing a monomer source comprising one or more organic compounds which are capable of polymerization, wherein at least one organic compound is prolinol; creating a plasma of said monomer source; and contacting at least a portion of a surface with the plasma to provide a plasma polymer coated surface. Advantageously, such methods provide an animal-free, synthetic, chemically defined surface that mimics a collagen coated surface for cell culture. Advantageously, such methods not only reduce the cost and/or issues associated with animal-derived collagen but are also amenable to large scale manufacturing.

The invention discloses a prolinol derivative induced chiral MOFs material with asymmetric catalysis, which belongs to the technical field of a chiral catalytic material. L-BCIP or D-BCIP is used as a chiral source; 5,5'-methylene diiso-phthalic acid, 4,4'-biphenyl acid, 3,3',4,4'-biphenyltetrazole acid or 4,4'-sulfonyl terephthalic acid is used as a connecting ligand; Ln3+ is used as a node; a three-dimensional hole channel structure is constructed by a hydrothermal method; the general formula is as follows: Ln<3+>+L+L-BCIP or D BCIP->Ln-L, wherein Ln<3+> is a rare earth metal ion; L is a connecting ligand; L-BCIP is L-N-tert-butoxycarbonyl-2-imidazole-1-pyrrolidine; and D-BCIP is D-N tert-butoxycarbonyl-2-imidazole-1-pyrrolidine. The material can be used as a heterogeneous catalyst used for an asymmetric silicon cyanation reaction; therefore, the catalyst can be recycled with a yield of 100% and ee value of 99%; and the chiral MOFs material has good application prospect in the aspects of synthesis of pure enantiomer compounds, synthesis of medical intermediates and the like. The material can be recycled after proper treatment.

The invention discloses a novel synthesizing method of dapoxetine, wherein a series of reactions are carried out on trans-cinnamaldehyde and N-carbobenzoxy hydroxylamine which serve as initiative raw materials under the action of a self-prepared catalyst (s)-alpha-alpha-diisopropyl dimethyl tert-butyl silicon oxygroup prolinol, so that an important intermediate of the dapoxetine, namely an important chiral intermediate (S)-3-amino-3-phenyl propyl alcohol (compound 4), is obtained. The invention further discloses a preparation method of capecitabine, wherein the compound serving as a raw material is methylated and protected by hydroxyl and then reacts with 1-naphthol to form a salt, so that the capecitabine is obtained. The preparation method is easy in raw material obtainment, good in stereoselectivity and high in yield, thereby being suitable for industrial production.

The invention discloses a synthetic method of a benzopyran chiral compound. The method comprises the following steps: a compound with the structural formula I and a compound with the structural formula II carry out the condensation reaction to generate a compound with the structural formula III, and the compound with the structural formula III is oxidized to obtain the benzopyran chiral compound; the chemical additive adopts a benzoic acid or a substituted benzoic acid compound; and the chiral catalyst is a diphenyl prolinol ester compound or dinaphthyl prolinol ester compound. The synthetic method has the advantages that under the mild condition, relatively cheap raw materials are used, the benzopyran chiral compound derivate is synthesized with high yield, and the derivate is high in optical purity, accessible in raw material, and beneficial for large-scale production and application.

The invention provides an avanafil intermediate A and an avanafil intermediate B, and a synthetic method of the avanafil intermediates A and B and avanafil. The synthetic method of the avanafil comprises the following steps: reacting a compound with the formula (I) with 2-methylaminopyrimidine at a temperature ranging from -10 DEG C to 5 DEG C to obtain the avanafil intermediate A; agitating the avanafil intermediate A with 3-chloro-4-methoxybenzylamine at the temperature ranging from 0 DEG C to 3 DEG C and reacting for 0.2-0.4 hour to obtain the avanafil intermediate B; and agitating the avanafil intermediate B with L-prolinol at the room temperature and reacting for 18-22 hours to obtain the avanafil. The structural formulas of the avanafil intermediates A and B and the compound with the formula (I) are shown in the specification. The avanafil intermediates A and B provided by the invention are simple in structure and good in product quality; the cost of the synthetic method is low; the synthetic route of the whole process is short and reaction steps are few, so that the reaction time is shortened and the yield and the purity of the avanafil intermediates A and B, and the avanafil are also improved.

The invention provides a new synthesis method for crizotinib. An atomic economic reaction is adopted to reduce environmental pollution. A high-optical purity raw material is obtained by chiral prolinol induced chiral reduction; a chiral centre is constructed through an SN2 substitution reaction; post-processing and purification difficulties caused by Mitsunobu reaction are overcome. Malononitrile derivative is constructed by adopting a coupling reaction of malononitrile and bromo-pyridinium derivative; N,N-dicarboamide derivatives are obtained by performing aminolysis on N,N-dimethylamine hydrochloride; in the N,N-dicarboamide derivatives, N,N-dimethylamine serving as an easy-to-leave group and hydrazine perform a ring closing reaction to construct a pyrazolone ring, so that an expected final product, namely crizotinib, is obtained. According to the method, though continuous steps are used, the reaction of each step is high, the optical purity is high, and the total yield is also high. In addition, raw materials used in the synthesis method are low in cost and easily obtained; the using amount of a catalyst is small; total cost is easy to control. An operating process is simple and convenient and easy to control, and is suitable for industrial production.

The invention relates to the field of the organic chemistry synthesis and in particular relates to a synthesis method of avanafil. The method comprises the following steps: carrying out nucleophilic substitution on raw materials which are 4-chloro-5-ethoxycarbonyl-2-methylthiopyrimidine and 3-chloro-p-methoxy benzyl amine hydrochloride to obtain 4-(3-chloro-4-methoxy benzyl amine hydrochloride)-5-ethoxycarbonyl-2-methylthiopyrimidine, then sequentially carrying out oxidation reaction, nucleophilic reaction with L-prolinol, esterolysis and dehydration synthesis to finally obtain avanafil. The method has the advantages that the used raw materials are cheap and easily available; the cost is low; the operation is simple and convenient; the prepared final product has few impurities and is of a solid state. The final product can be directly re-crystallized to obtain a pure product; the product is high in purity and suitable for industrial production.

The invention discloses a making method and application of chiral sulfonamide amide-alcohol ligand based on proamide-alcohol, which is characterized by the following: adopting L-proamide-alcohol as raw material; making each ligand framework possess 1-3 chiral center; proceeding selectivity loop-opening reaction for cycloethyliminum; improving receiving rate obviously; adopting chiral sulfonamide amide-alcohol ligand and similarity as catalyst ligand in the asymmetrical synthetic reaction; fitting for applying in the asymmetrical diethyl zinc additioning reaction, alkynyl zinc additioning reaction for carbonyl compound, reducing reaction and aldehyde alcohol condensing reaction.

The invention discloses optically active 3-substituted indole derivatives as well as a synthesis method and an application thereof. The optically active 3-substituted indole derivatives are with structures as shown in a formula (Ia) and a formula (Ib). The target products which are the optically active 3-substituted indole derivatives are prepared through one-step reaction at the temperature of 0-40 DEG C, wherein the raw materials include a diazo compound, an indole derivative and an alpha, beta-unsaturated aldehyde, the water absorbent is a 4-angstrom molecular sieve, the catalysts include a metal catalyst, chiral diaryl prolinol silicon ether and substituted benzoic acid, and the solvent is an organic solvent. The synthesis method disclosed by the invention has the advantages of high atom economy, high selectivity, high yield and mild reaction condition and is easy and safe to operate. The pair of optically active 3-substituted indole derivatives has high enantioselectivity and bioactivity and can be used for preparing antitumor medicines.

The invention discloses a compound (E)-3-(1-methylpyrrolidine-2-yl)-acrylic hydrochloride and a synthetic method. The compound is structurally as shown in a formula (I). The synthetic method of the compound comprises the following steps: using BOC-L-prolinol (or BOC-D-prolinol) as an initial material, and by oxidization, forming aldehyde; removing a BOC protective agent; then reacting with haloalkane; then by a Wittig reaction, synthesizing (S,E)-3-(1-methylpyrrolidine-2-yl)-ethyl acrylate; after hydrolysis, salifying to obtain (S,E)-3-(1-methylpyrrolidine-2-yl)-acrylic hydrochloride [or (R,E)-3-(1-methylpyrrolidine-2-yl)-acrylic hydrochloride]. The compound, as a medical intermediate, can be used for preparing quinazoline or quinolines medicine derivatives. The formula is shown in the description.

The invention provides an optical isomers pure cis 3-phenyl substituted s-proline derivative synthesis method. A route is as follows: taking the substituted cinnamaldehyde and nitroethyl alcohol as raw materials, taking (S)-diphenyl prolinol trimethyl silicyl oxide as an asymmetric catalyst, and obtaining the optical isomers pure cis 3-phenyl substituted s-proline derivative through asymmetric michael addition reaction, hydrogenation and boc protection reaction, and oxidation and deprotection reaction. The synthesis method has the advantages of high yield, good three-dimensional selectivity, mild reaction conditions, convenient post-treatment, no need of column chromatography purification, low cost and the like, and is a synthesis route with industrial prospect.

The invention relates to a chiral inducer for synthesizing (1R,2S)-Bedaquiline. Di(isopropyl)lithium ammonium takes off benzyl-bit protons from 6-bromo-3-benzyl-2-methoxy quinoline at a low temperature in the presence of the chiral inducer, i.e., lithium N-benzyl-L-prolinol and then is subjected to addition with 3-dimethylamino-1-naphthyl-1-acetone. Chiral o-amino lithium alkoxide remarkably increases the proportion of a target enantiomer, i.e., (1R,2S)-Bedaquiline and can be used for further preparing a drug, i.e., (1R,2S)-Bedaquiline fumarate.

The invention provides a preparation method of avanafil, and specifically relates to the technical field of pharmaceutical chemistry. The preparation method of avanafil comprises the following steps:sequentially carrying out cyclization and chlorination reactions on methyl thiourea sulfuric acid and diethyl ethoxymethylene malonate which serve as initial raw materials to obtain 4-chloro-2-methylthiopyrimidine-5-carboxylic acid ethyl ester; then substituting and hydrolyzing with 3-chloro-4-methoxybenzylamine; condensing with 2-pyrimidinemethanamine to obtain a key intermediate, namely, 4-[(3-chloro-methoxybenzyl)amino]-2-methylthio-N-(2-pyrimidine methyl)-5-pyrimidine formamide; oxidizing the intermediate and reacting with L-prolinol to generate the avanafil. The preparation method has theadvantages of easy availability of raw materials, easiness and convenience in operation, mild reaction conditions and higher product yield.

The invention relates to a Tamiflu intermediate and a synthesis method thereof, solving the technical problems of effectively reducing the production cost of the Tamiflu intermediate and effectively improving the yield of the Tamiflu intermediate and the content of the Tamiflu intermediate in a product. The method comprises the following steps: 1) catalytic reaction: in an organic solvent, reacting 3-pentyloxy acetaldehyde (1) and 3-nitro ethyl acrylate (2) in a molar ratio of 2: (1-2) in the presence of salt which is prepared by premixing (R)-N,N-dimethlbenzylamine prolinol silicon ether (3) with Bronzed acid in a molar ratio of 1: (1-8), so as to obtain an addition product (4); 2) carrying out reaction on the addition product (4) and 2-(diethoxy, phosphoryl) ethyl acrylate (5) in a molar ratio of 1: (1-2) and carrying out a reaction on cesium carbonate and the 2-(diethoxy, phosphoryl) ethyl acrylate (5) in a molar ratio of 2:1, so as to produce a produce (6); and 3) carrying out michael addition on the product (6) and p-methylthiophenol in a molar ratio of 1: (2-10), so as to obtain cyclohexane derivative, namely Tamiflu intermediate.

The invention discloses serial water-soluble hydroxycamptothecine naphthenic amino alcoholderivative. The serial water-soluble hydroxycamptothecine naphthenic amino alcohol derivative is synthesized by leading naphthenic amino alcohol methylene into a hydroxycamptothecine structure for the first time; and the hydroxycamptothecine with strong cell toxicity is decorated into the hydroxycamptothecine naphthenic amino alcohol derivative with medium cell toxicity. Therefore, the selectivity of induction of tumor cell apoptosis is improved; the situation that the hydroxycamptothecine prolinol has special hydrogenation reduction metabolic pathway in the body is found out for the first time; existing camptothecin derivatives do not have special hydrogenation reduction metabolic pathway; and active oxygen in the cell can be controlled, so as to inhibit cell proliferation, selectively induce cancer cell apoptosis, and inhibit cell inflammatory necrosis. Normal cell function is not affected.

The invention relates to the technical field of environmental protection, in particular to a prolinol rapid desulfurizer and a preparation method thereof. The problems that in the prior art, the visible light utilization rate is very low, point location requirements of various catalytic reactions are difficult to meet at the same time, meanwhile, photo-generated electron hole pairs are easy to compound, and the quantum efficiency is low are solved. The invention provides the prolinol rapid desulfurizer, the general formula of the desulfurizer is shown in the specification, wherein R1 to R5 areH, OCH3, NO2, X (F, Cl, Br), COOH and CF3. The desulfurizer is formed by condensation of R1 to R5 substituted phenylacetaldehyde and 2,3-dimethyl-2,3-dihydroxylamino butane, and R1 to R5 are respectively and independently selected from H, OCH3, NO2, halogen, COOH and CF3. The preparation method is simple, raw materials are easy to obtain, operation is easy, and the method is suitable for large-scale industrial production.

The invention discloses a method for preparing L-prolinol through high-pressure hydrogenization of L-proline. According to the method, L-proline is reduced for 4-12h in a solvent at the temperature of 120-180DEG C under the reaction pressure of 4-10MPa in the presence of a catalyst and catalytic acid, to obtain a target product L-prolinol, wherein the solvent is isopropanol preferably, the catalyst is 5% Ru/C preferably, and the catalytic acid is phosphoric acid preferably. The method for preparing L-prolinol is short in process route, high in yield and simple for aftertreatment.

The invention discloses a radiation protection compound with a structural general formula (I) or (II). The synthesis method comprises the steps: enabling triphenylphosphine to react with 6-bromohexanoic acid or 1,6-dibromohexane to obtain a triphenylphosphine cationic compound, sequentially performing acylation, etherification, reduction and oxidation on L-prolinol or D-prolinol, and combining with the triphenylphosphine cationic compound to obtain TPP-L/D-NIT-1 or TPP-L/D-NIT-2; the radiation protection compound is applied to the anti-radiation damage pharmaceutical composition. The radiationprotection compound is a mitochondria targeting nitroxide free radical compound with chirality and has an obvious radiation protection effect at an animal level, and a chiral prolinol structural unitin the radiation protection compound is similar to a proline structure in a biological organism, so that the biocompatibility is better; the synthesis method disclosed by the invention is mild in condition and good in reproducibility; the radiation protection compound provided by the invention has relatively high practical value.

The invention provides an asymmetric synthesis method of duloxetine intermediate-(S)-N, N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propylamine, which mainly comprises the following steps that: the (S)-N, N-dimethyl-3-hydroxy-3-(2-thienyl)-1-propylamine is obtained by reduction in the presence of (R)-(+)-alpha alpha-diaryl prolinol or (R)-(+)-alpha, alpha-diaryl prolinol silyl ether which is used as a catalyst and metal hydride complexes such as sodium borohydride and potassium borohydride which are used as a reducing agent. The method is simple and feasible, has high yield and optical purity, and is suitable for large-scale production.

The invention provides a synthesis method of R-diphenyl prolinol with a cyclopropane structure. The method comprises the following steps of: step 1, performing a Simmons-Smith cyclopropane reaction on (R)-1-N-tert-butoxycarbonyl-2,3-dihydro-2-pyrrole ethyl formate; step 2, respectively performing grignard reactions on enantiomers obtained by the step 1; and step 3, respectively performing amino-protection removing actions on reaction products obtained by the step 2, thereby obtaining the R-diphenyl prolinol with the cyclopropane structure. The method is reasonable in process, simple to operate and low in cost, and can be used for obtaining the enantiomer products with optical purity while chiral preparation and separation are not required further. Thus, the method is ideal for synthesis of the R-diphenyl prolinol with the cyclopropane structure.

The invention relates to use of an aryloxy-functionalized prolinol chiral ligand for catalyzing the asymmetric addition reaction of chalcone compounds with benzotriazole. In the water-free and oxygen-free conditions containing protective atmosphere, alpha, beta-unsaturated ketones in the formula (1) and benzotriazoles react in the organic solvent at 40-20 DEG C under the catalyst action of the aryloxy-functionalized prolinol chiral ligand and rare earth metal amines, so as to obtain compounds shown in the formula (3) and the formula (4) which are described in the description, wherein R1 is selected from the group consisting of hydrogen, alkyl, halogen, methoxy, nitro or CF3; R2 is selected from the group consisting of phenyl, C1-C4 alkyl substitute phenyl, C1-C4 alkoxy substitute phenyl, halophenyl, furyl or thienyl; H2Ln is that aryloxy-functionalized prolinol chiral ligand; the structural formula of H2Ln is as shown in the formula (2), wherein R3, R4 are independently selected from C1-C4 alkyl, cumyl, hydrogen or halogen; RE[N(SiMe3)2]3 is the rare earth metal amine compound, wherein RE represents a rare earth metal and RE is selected from the group consisting of scandium, lanthanum, neodymium, samarium, yttrium or ytterbium.

The invention discloses an L-prolinol synthetic method. The method comprises the following steps that 1, ethyl alcohol is added in a reaction kettle, thionyl chloride is dropwise added at 10-15 DEG C, then, L-prolinol is added, the temperature is increased to 40 DEG C, a heat-preservation reaction is carried out for 10-12 h, the mixture is concentrated to be thick liquid after the reaction is finished, ethyl acetate is added for dissolution, the pH value is adjusted through triethylamine to be 7-8, and salt is filtered away to obtain L-proline ethyl ester; 2, the L-proline ethyl ester is in a methyl alcohol system, lithium chloride is added at 5-10 DEG C, the sodium borohydride is added many times, a heat-preservation reaction is carried out at 20-25 DEG C for 2-2.5 h, hydrochloric acid is added, heat-preservation hydrolysis is carried out for 2 h, methyl alcohol is recycled, the pH value is adjusted through 25% sodium hydroxide to be 12, a product is extracted through dichloromethane, anhydrous sodium sulfate drying is carried out, and filtering is carried out; 3, dichloromethane is recycled from mother liquid at 30-40 DEG C and normal pressure, oily matter is obtained, pressure reduction and distillation are carried out, and therefore the pure L-prolinol is obtained. According to the L-prolinol synthetic method, the reaction temperature is mild, the safety coefficient is low, no solid waste is produced, and environmental protection is achieved.