Patents by Inventor Zedu HUANG
Zedu HUANG has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11913055Abstract: Disclosed herein relates to biopharmaceuticals, and more particularly to a continuous flow method for preparing (R)-3-hydroxy-5-hexenoate. Carbonyl reductase and isopropanol dehydrogenase are co-immobilized onto an inert solid medium simultaneously to prepare a carbonyl reductase/isopropanol dehydrogenase co-immobilized catalyst, which is then filled into a microchannel reactor of the micro reaction system. A solution containing substrate 3-carbonyl-5-hexenoate is subsequently pumped into the microchannel reactor to perform an asymmetric carbonyl reduction reaction to obtain (R)-3-hydroxy-5-hexenoate.Type: GrantFiled: October 19, 2021Date of Patent: February 27, 2024Assignee: Fudan UniversityInventors: Fener Chen, Dang Cheng, Zedu Huang, Chen Hu, Meifen Jiang, Minjie Liu, Huashan Huang
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Patent number: 11905229Abstract: A method of synthesizing diclofenac sodium, including: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide; subjecting 2-chloro-N-phenylacetamide and 2,6-dichlorophenol to condensation reaction to obtain 2-(2,6-dichlorophenoxy)-N-phenylacetamide; subjecting 2-(2,6-dichlorophenoxy)-N-phenylacetamide to Smiles rearrangement in the presence of an inorganic base to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide to Friedel-Crafts alkylation in the presence of a Lewis acid catalyst to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one to hydrolysis in the presence of an inorganic base to obtain diclofenac sodium.Type: GrantFiled: February 22, 2023Date of Patent: February 20, 2024Assignee: Fudan UniversityInventors: Fener Chen, Dang Cheng, Lulu Wang, Ge Meng, Yingtang Ning, Zedu Huang
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Patent number: 11802299Abstract: An enzyme-catalyzed method of synthesizing (2S,3R)-2-substituted aminomethyl-3-hydroxybutyrate, including: preparing engineered bacteria containing a carbonyl reductase SsCR-encoding gene; preparing a resting cell suspension of the engineered bacteria; preparing a culture containing carbonyl reductase; and mixing the culture containing carbonyl reductase with substrate 2-substituted aminomethyl-3-one butyrate, glucose dehydrogenase, a cosolvent, glucose and a cofactor followed by asymmetric carbonyl reduction to obtain (2S,3R)-2-substituted aminomethyl-3-hydroxybutyrate. The amino acid sequence of the carbonyl reductase is shown in SEQ ID NO.1.Type: GrantFiled: December 8, 2021Date of Patent: October 31, 2023Assignee: Fudan UniversityInventors: Fener Chen, Yuan Tao, Zedu Huang, Dang Cheng, Ge Meng
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Publication number: 20230234911Abstract: A method of synthesizing diclofenac sodium, including: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide; subjecting 2-chloro-N-phenylacetamide and 2,6-dichlorophenol to condensation reaction to obtain 2-(2,6-dichlorophenoxy)-N-phenylacetamide; subjecting 2-(2,6-dichlorophenoxy)-N-phenylacetamide to Smiles rearrangement in the presence of an inorganic base to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide to Friedel-Crafts alkylation in the presence of a Lewis acid catalyst to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one to hydrolysis in the presence of an inorganic base to obtain diclofenac sodium.Type: ApplicationFiled: February 22, 2023Publication date: July 27, 2023Inventors: Fener CHEN, Dang CHENG, Lulu WANG, Ge MENG, Yingtang NING, Zedu HUANG
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Patent number: 11708363Abstract: Disclosed herein relates to organic synthesis, and more particularly to a method for preparing a key intermediate for the synthesis of statins. The key intermediate is 2-[(4R,6S)-6-[(benzo[d]thiazol-2-ylthio)methyl]-2,2-disubstituted-1,3-dioxan-4-yl] acetate of formula (I): where R1 is a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a monosubstituted or polysubstituted aryl group, or monosubstituted or polysubstituted aralkyl group; R2 is hydrogen, or monosubstituted or polysubstituted C1-C3 alkyl group, or halogen; and R3 and R4 are each independently a C1-C5 alkyl group, a C3-C7 cycloalkyl group, a C3-C7 cycloalkenyl group, a C1-C3 alkoxy group, a C6-C10 aryl group, or C7-C12 aralkyl group. In the method, a halomethyl compound and a thiol reagent are subjected to nucleophilic substitution in an organic solvent to synthesize a thioether, which then undergoes ketal exchange reaction with a carbonyl compound (V) in the presence of an organic acid to obtain a target product.Type: GrantFiled: September 28, 2021Date of Patent: July 25, 2023Assignee: Fudan UniversityInventors: Fener Chen, Dang Cheng, Minjie Liu, Zedu Huang, Yuan Tao, Jiaqi Wang
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Patent number: 11555008Abstract: A method for preparing L-carnitine using a micro-reaction system. (R)-4-halo-3-hydroxybutyrate was subjected to quaternization and hydrolysis in an aqueous trimethylamine solution in the presence of an inorganic base in a micro-channel reactor to produce the L-carnitine.Type: GrantFiled: December 15, 2020Date of Patent: January 17, 2023Assignee: Fudan UniversityInventors: Fener Chen, Dang Cheng, Minjie Liu, Meifen Jiang, Zedu Huang, Zexu Wang, Jiaqi Wang
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Patent number: 11441163Abstract: An enzyme-catalyzed synthesis of (1S,5R)-bicyclolactone. A first genetically-engineered bacterium containing Baeyer-Villiger monooxygenase gene and a second genetically-engineered bacterium containing glucose dehydrogenase gene are constructed and then suspended with culture medium to prepare a first suspension and a second suspension, respectively. The first and second suspensions are centrifuged to respectively produce a first supernatant containing Baeyer-Villiger monooxygenase and a second supernatant containing glucose dehydrogenase, which are mixed. The mixed supernatant is then mixed with a raceme of a substituted bicyclo[3.2.0]-hept-2-en-6-one, a solvent, a hydrogen donor and a cofactor to perform an asymmetric Baeyer-Villiger oxidation to produce the (1S,5R)-bicyclolactone, where an amino acid sequence of the Baeyer-Villiger monooxygenase is shown in SEQ ID NO:1.Type: GrantFiled: September 30, 2020Date of Patent: September 13, 2022Assignee: Fudan UniversityInventors: Fener Chen, Kejie Zhu, Zedu Huang, Dang Cheng, Jiaqi Wang, Yuan Tao
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Patent number: 11345941Abstract: This application relates to biological pharmacy and biochemical engineering, and more particularly to a method of preparing a (S)-1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline compound. This method includes: subjecting a 1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline raceme as a substrate to selective oxidation in the presence of a monoamine oxidase and the non-selective reduction to prepare the (S)-1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline compound, where the monoamine oxidase has an amino acid sequence as shown in SEQ ID NO: 1 or an amino acid sequence having an identity of more than 80% with SEQ ID NO: 1. The kinetic resolution is carried out in the presence of the monoamine oxidase as a catalyst and a reductant, and the resulting product has a high chiral purity.Type: GrantFiled: February 29, 2020Date of Patent: May 31, 2022Assignee: FUDAN UNIVERSITYInventors: Fener Chen, Zedu Huang, Zhining Li, Jiaqi Wang
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Patent number: 11299451Abstract: A method for synthesizing 2-(1-cyclohexenyl)ethylamine. Cyclohexanone (II) is reacted with a Grignard reagent in a first organic solvent to produce 1-vinylcyclohexanol (III), which is then subjected to chlorination and rearrangement reaction with a chlorinating reagent in a second organic solvent in the presence of an organic base to synthesize (2-chloroethylmethylene)cyclolxane (IV). Then (2-chloroethylmethylene)cyclohexane (IV) and urotropine are subjected to quaternization in a third organic solvent to synthesize N-cyclohexylidene ethyl urotropine hydrochloride (V). Finally, the N-cyclohexylidene ethyl urotropine hydrochloride (V) undergoes hydrolysis and rearrangement reaction in a solvent in the presence of an inorganic mineral acid to synthesize 2-(1-cyclohexenyl)ethylamine (I).Type: GrantFiled: November 19, 2020Date of Patent: April 12, 2022Assignee: Fudan UniversityInventors: Fener Chen, Dang Cheng, Zedu Huang, Zhining Li, Meifen Jiang, Yuan Tao
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Publication number: 20220090151Abstract: An enzyme-catalyzed method of synthesizing (2S, 3R)-2-substituted aminomethyl-3-hydroxybutyrate, including: preparing engineered bacteria containing a carbonyl reductase SsCR-encoding gene; preparing a resting cell suspension of the engineered bacteria; preparing a culture containing carbonyl reductase; and mixing the culture containing carbonyl reductase with substrate 2-substituted aminomethyl-3-one butyrate, glucose dehydrogenase, a cosolvent, glucose and a cofactor followed by asymmetric carbonyl reduction to obtain (2S, 3R)-2-substituted aminomethyl-3-hydroxybutyrate. The amino acid sequence of the carbonyl reductase is shown in SEQ ID NO.1.Type: ApplicationFiled: December 8, 2021Publication date: March 24, 2022Inventors: Fener CHEN, Yuan TAO, Zedu HUANG, Dang CHENG, Ge MENG
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Publication number: 20220056489Abstract: A method for the continuous flow synthesis of (R)-4-halo-3-hydroxy-butyrate using a micro-reaction system. The micro-reaction system includes a micro-mixer, a certain number of micro-reaction units that are successively connected in series, a pH regulating system and a back pressure valve. The micro-reaction unit is composed of a micro-channel reactor and a pH regulator that are sequentially connected with each other. A substrate solution containing halogenated acetoacetate and a biocatalyst solution are simultaneously pumped into the micro-reaction system to enable continuous flow biocatalytic asymmetric reduction reaction of the halogenated acetoacetate to obtain the target product (R)-4-halo-3-hydroxy-butyrate.Type: ApplicationFiled: November 2, 2021Publication date: February 24, 2022Inventors: Fener CHEN, Dang CHENG, Zedu HUANG, Minjie LIU, Huashan HUANG, Meifen JIANG, Lulu WANG
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Publication number: 20220033863Abstract: Disclosed herein relates to biopharmaceuticals, and more particularly to a continuous flow method for preparing (R)-3-hydroxy-5-hexenoate. Carbonyl reductase and isopropanol dehydrogenase are co-immobilized onto an inert solid medium simultaneously to prepare a carbonyl reductase/isopropanol dehydrogenase co-immobilized catalyst, which is then filled into a microchannel reactor of the micro reaction system. A solution containing substrate 3-carbonyl-5-hexenoate is subsequently pumped into the microchannel reactor to perform an asymmetric carbonyl reduction reaction to obtain (R)-3-hydroxy-5-hexenoate.Type: ApplicationFiled: October 19, 2021Publication date: February 3, 2022Inventors: Fener CHEN, Dang CHENG, Zedu HUANG, Chen HU, Meifen JIANG, Minjie LIU, Huashan HUANG
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Publication number: 20220017508Abstract: Disclosed herein relates to organic synthesis, and more particularly to a method for preparing a key intermediate for the synthesis of statins. The key intermediate is 2-[(4R, 6S)-6-[(benzo[d]thiazol-2-ylthio)methyl]-2,2-di substituted-1,3-dioxan-4-yl] acetate of formula (I): where R1 is a C1-C8 alkyl group, a C3-C8 cycloalkyl group, a monosubstituted or polysubstituted aryl group, or monosubstituted or polysubstituted aralkyl group; R2 is hydrogen, or monosubstituted or polysubstituted C1-C3 alkyl group, or halogen; and R3 and R4 are each independently a C1-C5 alkyl group, a C3-C7 cycloalkyl group, a C3-C7 cycloalkenyl group, a C1-C3 alkoxy group, a C6-C10 aryl group, or C7-C12 aralkyl group. In the method, a halomethyl compound and a thiol reagent are subjected to nucleophilic substitution in an organic solvent to synthesize a thioether, which then undergoes ketal exchange reaction with a carbonyl compound (V) in the presence of an organic acid to obtain a target product.Type: ApplicationFiled: September 28, 2021Publication date: January 20, 2022Inventors: Fener CHEN, Dang CHENG, Minjie LIU, Zedu HUANG, Yuan TAO, Jiaqi WANG
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Publication number: 20220002224Abstract: A method for synthesizing 2-(1-cyclohexenyl)ethylamine. Cyclohexanone (II) is reacted with a Grignard reagent in a first organic solvent to produce 1-vinylcyclohexanol (III), which is then subjected to chlorination and rearrangement reaction with a chlorinating reagent in a second organic solvent in the presence of an organic base to synthesize (2-chloroethylmethylene)cyclolxane (IV). Then (2-chloroethylmethylene)cyclohexane (IV) and urotropine are subjected to quaternization in a third organic solvent to synthesize N-cyclohexylidene ethyl urotropine hydrochloride (V). Finally, the N-cyclohexylidene ethyl urotropine hydrochloride (V) undergoes hydrolysis and rearrangement reaction in a solvent in the presence of an inorganic mineral acid to synthesize 2-(1-cyclohexenyl)ethylamine (I).Type: ApplicationFiled: November 19, 2020Publication date: January 6, 2022Inventors: Fener CHEN, Dang CHENG, Zedu HUANG, Zhining LI, Meifen JIANG, Yuan TAO
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Publication number: 20210380524Abstract: A method for preparing L-carnitine using a micro-reaction system. (R)-4-halo-3-hydroxybutyrate was subjected to quaternization and hydrolysis in an aqueous trimethylamine solution in the presence of an inorganic base in a micro-channel reactor to produce the L-carnitine.Type: ApplicationFiled: December 15, 2020Publication date: December 9, 2021Inventors: Fener CHEN, Dang CHENG, Minjie LIU, Meifen JIANG, Zedu HUANG, Zexu WANG, Jiaqi WANG
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Publication number: 20210355516Abstract: An enzyme-catalyzed synthesis of (1S,5R)-bicyclolactone. A first genetically-engineered bacterium containing Baeyer-Villiger monooxygenase gene and a second genetically-engineered bacterium containing glucose dehydrogenase gene are constructed and then suspended with culture medium to prepare a first suspension and a second suspension, respectively. The first and second suspensions are centrifuged to respectively produce a first supernatant containing Baeyer-Villiger monooxygenase and a second supernatant containing glucose dehydrogenase, which are mixed. The mixed supernatant is then mixed with a raceme of a substituted bicyclo[3.2.0]-hept-2-en-6-one, a solvent, a hydrogen donor and a cofactor to perform an asymmetric Baeyer-Villiger oxidation to produce the (1S,5R)-bicyclolactone, where an amino acid sequence of the Baeyer-Villiger monooxygenase is shown in SEQ ID NO:1.Type: ApplicationFiled: September 30, 2020Publication date: November 18, 2021Inventors: Fener CHEN, Kejie ZHU, Zedu HUANG, Dang CHENG, Jiaqi WANG, Yuan TAO
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Patent number: 10961515Abstract: Disclosed herein are a carbonyl reductase variant and its use in the preparation of (R)-4-chloro-3-hydroxybutyrate. The carbonyl reductase variant is obtained by mutating phenylalanine-85 in an amino acid sequence as shown in SEQ ID NO:4 to methionine. An amino acid or amino acids at one or more positions other than position 85 in the amino acid sequence of the carbonyl reductase may be further replaced. The application also provides a recombinant expression vector carrying the gene encoding the carbonyl reductase variant, a genetically-engineered bacterium carrying the carbonyl reductase variant gene and glucose dehydrogenase gene, and an application of this bacterium in the asymmetric reduction of 4-chloroacetoacetate to prepare (R)-4-chloro-3-hydroxybutyrate.Type: GrantFiled: June 17, 2020Date of Patent: March 30, 2021Assignee: Fudan UniversityInventors: Fener Chen, Zedu Huang, Zexu Wang, Minjie Liu
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Publication number: 20210087595Abstract: This application relates to biological pharmacy and biochemical engineering, and more particularly to a method of preparing a (S)-1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline compound. This method includes: subjecting a 1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline raceme as a substrate to selective oxidation in the presence of a monoamine oxidase and the non-selective reduction to prepare the (S)-1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline compound, where the monoamine oxidase has an amino acid sequence as shown in SEQ ID NO: 1 or an amino acid sequence having an identity of more than 80% with SEQ ID NO: 1. The kinetic resolution is carried out in the presence of the monoamine oxidase as a catalyst and a reductant, and the resulting product has a high chiral purity.Type: ApplicationFiled: February 29, 2020Publication date: March 25, 2021Inventors: Fener CHEN, Zedu HUANG, Zhining LI, Jiaqi WANG
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Patent number: 10662145Abstract: The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain.Type: GrantFiled: February 27, 2019Date of Patent: May 26, 2020Assignee: FUDAN UNIVERSITYInventors: Fener Chen, Lingdong Wang, Ge Meng, Zedu Huang, Dang Cheng, Haihui Peng, Guanfeng Liang
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Publication number: 20200055811Abstract: The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain.Type: ApplicationFiled: February 27, 2019Publication date: February 20, 2020Inventors: Fener CHEN, Lingdong WANG, Ge MENG, Zedu HUANG, Dang CHENG, Haihui PENG, Guanfeng LIANG