106results about How to "Good diastereoselectivity" patented technology

The invention discloses a recombinant carbonyl reductase sourced from Burkholderia gladioli ZJB-12126 as well as an encoding gene of the recombinant carbonyl reductase, a recombinant vector containing the gene, a recombinant gene engineering bacterium obtained by transforming the recombinant vector, and an application of the recombinant carbonyl reductase in asymmetrically reducing prochiral carbonyl compounds. According to the recombinant carbonyl reductase disclosed by the invention, by respectively taking 2-benzamidomethyl-3-ketone butyrate, 4-chloroacetoacetic acid ethyl ester (COBE), (R)-6-cyano-5-hydroxyl-3-carbonyl caproate tert-butyl ester and (4S)-3-[5-(4-fluorophenyl)-1,5-dioxopentyl]-4-phenyl-2-oxazolidinone as substrates, (2S, 3R)-2-benzamidomethyl-3-polyhydroxybutyrate, (S)-4-chloro-3-ethyl hydroxybutyrate, 6-cyano-(3R, 5R)-dihydroxyhexanoic acid tert-butyl ester and (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxyl valeryl]-4-phenyl-1,3-oxo-azacyclopentane-2-ketone with high optical purity are prepared by virtue of biocatalytic reaction, wherein the biocatalytic reaction can be performed by using recombinant escherichia coli as a biocatalyst, and thus optional new enzyme sources can be provided for biocatalytic synthesis of chiral intermediates of medicines.

The present invention provides compounds of formula (I):

as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

A method is disclosed for preparing a synthetic intermediate for treprostinil via a stereoselective alkyne addition reaction using a chiral inducing agent. Also described are methods of preparing treprostinil or a pharmaceutically acceptable salt thereof comprising the alkyne addition reaction as well as novel intermediates useful for synthesis prostacyclin derivatives. A functional alcohol protecting group protects the alcohol group from participating in reactions that are occurring in other parts of the molecule. The intermediate is later deprotected prior to conversion and hydrolyzing to obtain the final treprostinil product.

The invention relates to a fluorescent labeled organic boron/nitrogen Lewis acid and base bifunctional catalyst and a preparation method thereof. The catalyst is characterized by being prepared by the following step: by taking a quinoline amide compound and a cheap sodium tetraphenylborate derivative as raw materials, cheap and easily available single element iodine as a catalyst and a common organic solvent as a reaction solvent, performing a reaction for a while at a certain temperature to obtain the bifunctional organic boron/nitrogen Lewis acid and base catalyst with a high yield and high selectivity. The catalyst is good in stability and recyclable, and has very good diastereoselectivity in a Mannich reaction. The method has the advantage s of being relatively low in cost, high in yield, simple and convenient to operate, pollution-free and the like, and has certain feasibility for realizing industrial production.

The invention belongs to the field of asymmetric synthesis, and particularly relates to a novel method for catalyzing and synthesizing a chiral 4-nitryl-3, 5-diaryl cyclohexanone compound by chiral thiocarbamide as a catalyst. The method comprises the following steps of: (1) reacting by taking diketene and nitromethane as a reaction substrate, quinine-derived thiocarbamide as a chiral catalyst and methylbenzene as solvent at the temperature of between 20 and 25 DEG C for 24 to 72 hours to generate a Michael addition product; and (2) reacting by taking the Michael addition product obtained in the step (1) as a reactant, potassium hydroxide as a catalyst and ethanol as solvent at the temperature of between 0 and 10 DEG C for 0.5 to 2 hours to obtain a chiral 4-nitryl-3, 5-diaryl cyclohexanone derivative. The novel method for synthesizing the chiral 4-nitryl-3, 5-diaryl cyclohexanone compound has the advantages of readily available materials and mild reaction conditions and is easy and convenient to operate, and a reaction system is insensitive to air, aqueous vapor and the like and aftertreatment is convenient, so the chiral 4-nitryl-3, 5-diaryl cyclohexanone compound is suitable for industrial production. Simultaneously, the synthetic method has the characteristics of high yield and excellent diastereoselectivity and enantioselectivity.

The invention belongs to the field of asymmetric catalysis, and specifically relates to a method for synthesizing a novel chiral 2',5-dicarbonyl-3-aryl spiro[cyclohexane-1,3'-indole]-2,2-dinitrile compound. According to the invention, chiral primary amine derived from quinine is adopted as a catalyst, and chiral or achiral Brownst acid is adopted as a co-catalyst, such that the compound is synthesized under catalyzing. According to the invention, the chiral 2',5-dicarbonyl-3-aryl spiro[cyclohexane-1,3'-indole]-2,2-dinitrile compound is synthesized through a dual-Michael addition reaction of an isatin malononitrile condensation substance and methyl aryl alpha,beta-unsaturated ketone. The synthesizing method is advantaged in simple raw materials which are easy to acquire, convenient operation, and good substrate compatibility. A plurality of chiral centers can be established with a one-kettle method. Under a high-temperature reaction condition, high yield and high conversion frequency are realized, and excellent enantioselectivity and excellent diastereoselectivity can be realized.

The invention relates to polysubstituted tetrahydrofuran derivatives and a chemical synthesis method thereof. The chemical synthesis method comprises the following steps: carrying out one-step reaction on raw materials (a diazo compound and a 3-hydroxyl-carbonyl flavone compound) in an organic solvent in the presence of a metal catalyst and an additive which is a molecular sieve shown in the specification; and carrying out column chromatography purification to obtain the target product. The chemical synthesis method of the polysubstituted tetrahydrofuran derivatives has the advantages of environmental benefit, step economy, atom economy, diastereoselectivity and high yield; in addition, the reaction conditions are mild, the applicability of the substrate range is wide and the operation is simple and safe. The invention discloses that the polysubstituted tetrahydrofuran derivatives with multiple chiral centers have PTPlB inhibiting effect; and therefore, the polysubstituted tetrahydrofuran derivatives are important chemical engineering, chemical and medical intermediates and have a wide prospect in the field of pharmaceutical chemicals.

The invention discloses a preparation method of multi-substituted indanol derivatives. The diazo compound, alcohol and o-formyl chalcone are used as raw materials, a metal catalyst is used as a catalyst, an organic solvent is used as a solvent, and a molecular sieve is used as a water absorbent; and the multi-substituted indanol derivatives are obtained by one-step reaction. According to the preparation method disclosed by the invention, the raw materials are easily available, the operation is simple and safe, and the method is suitable for industrial production.

The invention discloses a trifluoromethyl substituted continuous quaternary carbon center cyclopropane derivative and a synthetic method, belonging to the technical field of synthesis of medicine chemical industry. The synthetic method comprises the following steps: adding N-tosyl hydrazone, trifluoromethyl ketone, alkali, a phase transfer catalyst and a solvent into a reactor, carrying out reaction under stirring at 70 to 90 DEG C for 12 to 24 hours, after the reaction is completed, carrying out cooling to room temperature, filtering obtained reaction liquid, carrying out vacuum evaporation and removing the solvent so as to obtain a crude trifluoromethyl substituted continuous quaternary carbon center cyclopropane derivative, and carrying out purifying through column chromatography so as to obtain the trifluoromethyl substituted continuous quaternary carbon center cyclopropane derivative. The method provided by the invention avoids using a transition metal catalyst and uses non-toxic, cheap and easily-available raw materials; the reaction has good adaptability to functional groups and wide adaptability to a substrate, has high product yield and good non-reflect selectivity, can be enlarged to gram-grade scale production and synthesis, and is favorable for industrial production; meanwhile, the obtained trifluoromethyl substituted continuous quaternary carbon center cyclopropane derivative has extensive application in the fields of pesticides, medicines and materials.

The invention discloses a synthesis method of a spiro hydroxyindolocyclopentane beta-exo fat compound. The synthesis method comprises the following step: by taking phenyl unsaturated aldehyde and unsaturated ketoacid ester as reactants and by taking n-heterocyclic carbene as a catalyst, performing reaction, thus obtaining the spiro hydroxyindolocyclopentane beta-exo fat compound. According to the method disclosed by the invention, the raw materials are simple and readily available; the reaction conditions are mild; post-treatment is simple and convenient; the synthesis method is wide in application substrate range, high in yield and high in diastereoselectivity and enantioselectivity; therefore, a synthesized product can be used for synthesizing an intermediate of a medicine and a pesticide.

The invention discloses a method for synthetizing 2,3-disubstituted dihydrobenzofuran. Kinds of substituted 2,3-disubstituted dihydrobenzofurans can be obtained from simple ylide and substituted phenol by reactions under an alkali catalytic condition. The method disclosed by the invention is simple and practical in operation, available in raw materials, high in yield, and good in diastereoselectivity.

The invention discloses a preparation method of a polysubstituted pyrroloquinoline derivate. The preparation method is characterized in that aminochalcone and aldehyde are condensed to obtain chalcone imine; the chalcone imine and glycinate imine are subjected to series cyclizing through Michael/Mannich and then are subjected to acidizing, and thus the polysubstituted pyrroloquinoline derivate containing four chiral centers, as shown in formula (I), can be generated based on high diastereoselectivity. The preparation method is on the basis of series reaction, and has the advantages that the environmental protection is achieved; the synthesizing steps are simple and convenient; the atom economy is ensured; the diastereoselectivity is high; in addition, the reaction conditions are mild; the substance is wide in applicable scope; the operation is simple and safe; the preparation method is applicable to industrial production.

The present invention discloses a spiro oxindole imidazolinyl oxazepine compound and a synthesis method thereof, wherein particularly diazo oxindole and dibenzoxazepine are adopted as reactants, and synthesis is performed in a solvent under catalysis of iron trifluomethanesulfonate (II) or a p-toluenesulfonic acid monohydrate to obtain the product. According to the present invention, the method has characteristics of simple and easily-available raw materials, mild reaction conditions, simple and convenient post-treatment, wide substrate application range, high yield and high diastereoselectivity; and the synthesized product can be used for synthesizing the intermediate of drugs and insecticides.

The invention discloses a method for synthesizing a fluorine-containing quinolinone compound by electro-catalyzing indole by using an electrochemical micro-channel reaction device, which is characterized by comprising the following steps of respectively and simultaneously pumping a first solution containing an N-substituted 2-aryl indole compound shown as a formula I with a second solution containing a fluorine source and an electrolyte, reacting to obtain a reaction solution containing the fluorine-containing quinolinone compound as shown in the formula II. The micro-channel reaction device is used for preparing the fluorine-containing quinolinone compound, the reaction rate can be effectively controlled, the reaction time is shortened, continuous production is achieved, high diastereoselectivity is achieved, generation of by-products is reduced, the maximum yield can reach 98.7%, the refining process is simpler, and the product quality is improved; basically no amplification effect exists, and industrial amplification is facilitated.

The invention relates to a method for synthesizing a 1R,2R,3R-substituted cyclopentanone compound. The method comprises: carrying out a reaction on a compound 1 and a halogenated alkane in an organicsolvent under the actions of a strong alkali and a cuprous salt to obtain a compound 3, carrying out ester hydrolysis on the compound 3 under the action of an alkali or pancreatin, and carrying out deprotection by using a fluorine reagent to obtain the product. According to the present invention, the synthesis method has characteristics of high yield, high product purity, good diastereoselectivity, easy reaction control and simple post-treatment, is suitable for industrial production, and can synthesize high-purity and high-yield alprostadil, lubiprostone, and the analogs of misoprostol and limaprost. The compound 1 is defined in the specification.

3-aryl-3'-amino bis(quaternary carbon) bis(oxindole) compounds and a synthetic method and applications thereof are disclosed. The compounds are prepared from diazo compounds, N,N-disubstituted anilineand isatin imine compound by adopting rhodium acetate as a catalyst, an organic solvent as a solvent and a 4A molecular sieve as an additive through one-step reaction at room temperature. The methodhas advantages of efficient atom economy, high selectivity, a low dosage of the catalyst, simple and safe operation, and the like. The synthesized bis(quaternary carbon) bis(oxindole) compounds can beadopted as important medical and chemical intermediates and have wide application prospects in the medicinal field.

The invention discloses a preparation method of an organic boron-nitrogen fluorescent compound. The preparation method comprises the following steps of: adopting a quinoline amide compound, cheap sodium-tetraphenylborate type derivatives and carboxylic-acid type derivatives as raw materials, adopting cheap copper bromide or sodium bromide as a catalyst, adopting a common organic solvent as a reaction solvent, reacting for a period of time under a certain temperature, and obtaining a novel chiral organic boron-nitrogen fluorescent compound by high yield and high selectivity. The organic boron-nitrogen fluorescent compound is good in stability, can be recovered, has very good diastereoisomeric selectivity in aldehyde-ketone condensation reaction. The preparation method disclosed by the invention has the advantages of lower cost, high yield, simple operation and no pollution and the like, and has certain feasibility for realizing industrial production.

The invention provides a synthetic method for preparing a compound containing multiple-chiral center chromanone skeletons, which can effectively utilize chiral amine-in particular a, a-diaryl prolinol O-silyl ether--catalytic chromone electron-deficient diene compound and olefine aldehyde to generate Diels-Alder reaction required by asymmetric anti-electrons with high regioselectivity and high stereoselectivity and series vinylogy Aldol or series hemiacetal reaction under the mild reaction conditions and can also be used for synthesizing the compound with the multiple-chiral center dihydro-chromogenic ketone skeletons. The asymmetric synthetic method is reported for the first time and has the various advantages of cheap and easily-obtained catalyst, high catalytic activity, mild reaction condition, simplicity in operation, wide substrate application scope and high product area and enantioselectivity; and more importantly, the compound containing the various multiple-chiral center dihydro-chromogenic ketone skeletons prepared by the method possibly has special physiological activity or becomes an important synthetic intermediate body of a natural product.

The invention belongs to the technical field of organic synthesis and discloses a synthesis method of polysubstituted 4-phenyl chroman compounds. The structural formula of polysubstituted 4-phenyl chroman compounds is shown by formula I. The method involves non-metal catalyzed oxamichael addition and 1,6-tandem reaction conjugated addition under mild condition. The catalyst used in the invention is a commercial nonmetallic alkali, has low cost, is environmentally friendly and is easy to operate; the method disclosed in the invention has high yield, excellent diastereoselectivity, mild conditions, convenient post-treatment and easy separation and purification of products; the method of the invention is easy to produce on a large scale, and the amplified yield and diastereoselectivity can bemaintained.