72 results about "Butylone" patented technology

The invention relates to a gamma methyl ethyl ketone acid derivative represented by general formula (I), and contains gamma-aryl-alpha-amido-beta, its preparing process, pharmaceutical compositions containing them and use as medicament, in particular as medicament for treating osteoarthritis and tumor.

An azetidinone derivative represented by the general formula (1) (wherein OR1 is a protected hydroxyl group; R2 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group or a substituted or unsubstituted aromatic group) is reacted with an ester compound represented by the formula (2) (wherein CO2R3 is an esterified carboxyl group; X and Y are the same or different and represent individually a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted alkenylthio group, a substituted or unsubstituted aralkylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted alkyloxy group, a substituted or unsubstituted alkenyloxy group, a substituted or unsubstituted aralkyloxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted silyloxy group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted heterocyclic-thio group, a substituted or unsubstituted heterocyclic-oxy group, a substituted or unsubstituted acyl group, a substituted or unsubstituted ester group, a substituted or unsubstituted thio ester group, a substituted or unsubstituted amide group, a substituted or unsubstituted amino group, a hydrogen atom or halogen atom, or are taken together with each other to form a substituted or unsubstituted cycloalkan-2-on-1-yl group) in the presence of zinc and copper compounds to synthesis a 4-substituted azetidinone derivative represented by the formula (3) (wherein OR1, CO2R3, X and Y are as defined above).

The invention relates to a method for synthesizing 3-(Boc-aminomethyl)cyclobutanone. The method for synthesizing 3-(Boc-aminomethyl)cyclobutanone provided by the invention mainly solves the technicalproblems of high raw material cost and relatively difficult post-processing according to the existing synthesis method. The method for synthesizing 3-(Boc-aminomethyl)cyclobutanone provided by the invention comprises the following steps: 3-oxocyclobutanecarboxylic acid and trimethyl orthoformate are reacted in the methanol solution to generate a compound 1; the compound 1 and benzylamine are reacted in the methanol solution under an action of sodium methoxide to generate a compound 2; the compound 2 and sodium bis(2-methoxyethoxy)aluminiumhydride are reacted in tetrahydrofuran solution to generate a compound 3; the compound 3 is subjected to a Pd / C debenzylation and hydrogenation operation in the methanol solution to obtain a compound 4; the compound 4 and Boc2O are reacted in the methanolsolution to obtain a compound 5; the compound 5 is reacted in a 0.05 M hydrochloric acid solution generate a target compound 6. By performing an enzymatic catalyzed deglandulation action of on the corresponding prochiral 3-substituted cyclobutanone, a series of gamma-butyrolactone derivatives, including some spiro derivatives, can be obtained; and all the derivatives are inhibitors having good biological activity.

The invention discloses a (R)-omega-transaminase mutant and an application thereof in preparation of a sitagliptin intermediate. The mutant is obtained through multipoint mutation of arginine at the 77th site, leucine at the 181st site, arginine at the 130th site, tyrosine at the 139th site and threonine at the 273th site of an amino acid sequence shown as SEQ ID NO.1. According to the invention,a novel (R)-omega-TA recombinase is screened through a gene mining technology; molecular modification is carried out through a protein engineering technology; an (R)-omega-TA mutant catalyst with highenzyme activity, high substrate tolerance and high stereoselectivity is obtained; and the mutant can be used for asymmetric catalytic synthesis of the sitagliptin intermediate (R)-3-amino-1-(pyrrolidine-1-yl)-4-(2, 4, 5-trifluorophenyl) butan-1-one by taking a precursor ketone analogue 1-(pyrrolidine-1-yl)-4-(2, 4, 5-trifluorophenyl)-1, 3-butanedione as a substrate, and has higher conversion rate.

The invention discloses a method for synthesizing (R)-3-amino-1-butanol through double enzyme cascade catalysis. The method comprises the following steps: with 1, 3-butanediol as a substrate, carrying out a catalytic reaction with alcohol dehydrogenase to generate 4-hydroxy-2-butanone; and taking 4-hydroxy-2-butanone as a substrate, and generating chiral (R)-3-amino-1-butanol through a catalytic reaction of amine dehydrogenase or a mutant of the amine dehydrogenase. The invention provides a brand-new green biosynthesis route, and the chiral (R)-3-amino-1-butanol is catalytically synthesized by using cheap 1, 3-butanediol as a raw material through double-enzyme cell co-expression. Meanwhile, the method provided by the invention has a cofactor self-circulation system and has good economic benefits. The method has an important application value.

The invention discloses a preparation method of a sitagliptin intermediate and the sitagliptin intermediate prepared by the preparation method, the preparation method comprises the step that in the presence of an organic solvent with a boiling point not higher than 110 DEG C at a standard atmospheric pressure, carrying out transamino contact between transaminase and a substrate sitagliptin precursor ketone (2Z)-4-oxo-4-[3-(trifluoromethyl)-5, 6-dihydro-[1, 2, 4]triazolo[4, 3-a]pyrazine-7-(8H)-yl]-1-(2, 4, 5-trifluorophenyl) butyl-2-one to perform enzyme catalysis reaction so as to prepare the sitagliptin intermediate (3R)-3-amino-1-[3-(trifluoromethyl)-5, 6, 7, 8-tetrahydro-1, 2, 4-triazolo [4, 3-a] pyrazine-7-yl]-4-(2, 4, 5-trifluorophenyl) butyl-1-one, a mixed solution obtained by mixing a low-boiling-point organic solvent and the substrate is added into a premixing system containing the transaminase in a fed-batch mode, ketoreductase and a coenzyme regeneration system in a specific proportion are added into the premixing system, the substrate conversion rate is increased, and the substrate conversion rate can reach 99%.

The present invention relates to a polypeptide having an activity to asymmetrically reduce (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone to produce (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol isolated from a microorganism belonging to the genus Ogataea, a DNA encoding the polypeptide and a transformant that produces the polypeptide. The present invention moreover relates to a method of producing (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol utilizing the polypeptide or the transformant.Using the polypeptide or transformant of the present invention, optically active alcohols such as (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol and the like can be produced efficiently.

The invention provides a preparation method of fexofenadine, which comprises the following steps: by using bromobenzene as a raw material, carrying out Friedel-Crafts acylation reaction to obtain 4'-bromo-4-chlorophenone ; enabling 4'-bromo-4-chlorobutanone and 1-methoxy-1-(trimethylsiloxy)-2-methyl-1-propene to subjected to coupling reaction to obtain 2-[4-(4 -chloro-1-butyryl)phenyl]-2-methyl methyl propionate; and sequentially carrying out N-alkylation, carbonyl reduction and alkaline hydrolysis on 2-[4-(4 -chloro-1-butyryl)phenyl]-2-methylpropanoate to obtain fexofenadine. The method has the advantages of cheap and easily available raw materials, easiness in operation, high yield, low cost, no meta-isomer, suitability for industrial production and the like.

The invention discloses a synthesis method of a larotrectinib intermediate, and belongs to the field of drug synthesis. The method uses 4-chloro-1-(2, 5-difluorophenyl)butane-1-one (I) as the raw material to synthesize 5-(2, 5-difluorophenyl)-3, 4-dihydro-2H-pyrrole (III) through ammonolysis and ring closing one-pot method. The invention provides the synthesis method of the larotrectinib intermediate. The method is controllable in reaction process, easy to operate and high in yield.