公开(公告)号：US12194428B2

公开(公告)日：2025-01-14

申请号：US17467377

申请日：2021-09-06

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Minjie Liu ,  Huashan Huang ,  Meifen Jiang ,  Jiaqi Wang

IPC: B01F35/00 ,  B01F33/30 ,  B01F35/53

Abstract: A multi-layered micro-channel mixer includes a base plate and a cover plate. Two inlet fluid reservoirs, two inlet channels, two groups of fluid distribution channel networks, two groups of process fluid channels, an impinging stream mixing chamber, a fluid mixing intensification channel and an outlet buffer reservoir are provided on the base plate. Two fluids are fed into the two inlet fluid reservoirs, respectively. The fluids then flow into the process fluid channels via the inlet channels and the multi-stage fluid distribution channel networks, respectively. Then the two fluid streams ejected from the opposing process fluid channels impinges upon each other in the impinging stream mixing chamber. The mixed fluid is subjected to vortex or secondary flow generated by the baffles or the internals in the impinging stream mixing chamber and fluid mixing intensification channel, and finally the mixed fluid is discharged through the outlet buffer reservoir.

公开(公告)号：US11912685B2

公开(公告)日：2024-02-27

申请号：US17468447

申请日：2021-09-07

Applicant: Fudan University

Inventor： Fener Chen ,  Chunlin Zhuang ,  Li Ding

IPC: C07D401/12 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  A61P31/18

CPC classification number: C07D401/12 ,  A61P31/18 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12

Abstract: This application provides a biphenyl diaryl pyrimidine derivative with an aromatic heterocyclic structure, a pharmaceutically-acceptable salt, a stereoisomer, a hydrate and a solvate thereof, where the biphenyl diaryl pyrimidine derivative is shown in formula (I). This application also provides a pharmaceutical composition containing the biphenyl diaryl pyrimidine derivative, or a pharmaceutically-acceptable salt, a stereoisomer, a hydrate and a solvate thereof, and a pharmaceutically-acceptable carrier. This application further provides a method of treating AIDS by administering a therapeutically effective amount of the pharmaceutical composition to a patient in need.

公开(公告)号：US11802299B2

公开(公告)日：2023-10-31

申请号：US17545963

申请日：2021-12-08

Applicant: Fudan University

Inventor： Fener Chen ,  Yuan Tao ,  Zedu Huang ,  Dang Cheng ,  Ge Meng

IPC: C12P13/00

CPC classification number: C12P13/001 ,  C12Y101/01184

Abstract: 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.

公开(公告)号：US11447501B2

公开(公告)日：2022-09-20

申请号：US16986200

申请日：2020-08-05

Applicant: Fudan University

Inventor： Fener Chen ,  Yali Sang ,  Chunlin Zhuang

IPC: C07D495/04 ,  A61P31/18 ,  A61K31/519

Abstract: A biphenyl-containing diarylpyrimido compound of formula (I), which is prepared by reacting a 4-chloropyrimidine derivative with a biphenyl derivative in a solvent in the presence of a base. A pharmaceutically-acceptable salt of the compound (I) and a pharmaceutical composition containing the compound (I) or a pharmaceutically-acceptable salt thereof are also provided.

公开(公告)号：US11441163B2

公开(公告)日：2022-09-13

申请号：US17038081

申请日：2020-09-30

Applicant: Fudan University

Inventor： Fener Chen ,  Kejie Zhu ,  Zedu Huang ,  Dang Cheng ,  Jiaqi Wang ,  Yuan Tao

IPC: C12P17/04 ,  C12N1/20 ,  C12N9/02 ,  C12N15/70

Abstract: 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.

公开(公告)号：US11345941B2

公开(公告)日：2022-05-31

申请号：US16805742

申请日：2020-02-29

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Zedu Huang ,  Zhining Li ,  Jiaqi Wang

IPC: C12P17/12 ,  C12N9/06 ,  C12P41/00

Abstract: 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.

公开(公告)号：US12084427B2

公开(公告)日：2024-09-10

申请号：US17740275

申请日：2022-05-09

Applicant: Fudan University

Inventor： Fener Chen ,  Liangchuan Lai ,  Baijun Ye ,  Meifen Jiang

IPC: C07D401/12 ,  B01J4/00 ,  B01J8/02

CPC classification number: C07D401/12 ,  B01J4/001 ,  B01J4/008 ,  B01J8/02

Abstract: Disclosed is a method of continuously preparing N,N-Bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexamethylenediamine, which relates to chemical engineering. The Pt/C catalyst and the quartz sand are mixed uniformly and loaded to the continuous-flow fixed-bed reactor. Then, hydrogen gas and a substrate solution containing 2,2,6,6-tetramethyl-4-piperidinone and 1,6-hexanediamine are simultaneously fed to the micro-mixer and the continuous-flow fixed-bed reactor in sequence to undergo a continuous catalytic reductive amination to obtain the N,N-Bis(2,2,6,6-tetramethyl-4-piperidyl)-1,6-hexamethylenediamine.

公开(公告)号：US11834388B2

公开(公告)日：2023-12-05

申请号：US18172865

申请日：2023-02-22

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Lulu Wang ,  Ge Meng ,  Yingtang Ning

IPC: C07C227/18 ,  C07C227/40

CPC classification number: C07C227/18 ,  C07C227/40

Abstract: This application relates to pharmaceutical engineering, and more particularly to a continuous-flow preparation method of diclofenac sodium. The continuous-flow preparation method includes: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide (3); subjecting 2-chloro-N-phenylacetamide (3) and 2,6-dichlorophenol to continuous condensation to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5); subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5) and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6); subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6) to Friedel-Crafts alkylation in the presence of aluminum chloride to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (7); and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (7) to hydrolysis to obtain the diclofenac sodium.

公开(公告)号：US11554355B2

公开(公告)日：2023-01-17

申请号：US17467060

申请日：2021-09-03

Applicant: Fudan University

Inventor： Fener Chen ,  Meifen Jiang ,  Dang Cheng ,  Minjie Liu ,  Huashan Huang

IPC: B01J19/00 ,  C07D239/42

Abstract: Disclosed herein relates to pharmaceutical engineering, and more particularly to a micro reaction system and a method for preparing 2-methyl-4-amino-5-cyanopyrimidine using the same. An acetamidine hydrochloride solution and an (dimethylaminomethylene)malononitrile solution are separately pumped into the micro reaction system including a micromixer and an agitating microchannel reactor in communication at the same time for a continuous condensation-cyclization reaction to obtain 2-methyl-4-amino-5-cyanopyrimidine.

公开(公告)号：US10662145B2

公开(公告)日：2020-05-26

申请号：US16288031

申请日：2019-02-27

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Lingdong Wang ,  Ge Meng ,  Zedu Huang ,  Dang Cheng ,  Haihui Peng ,  Guanfeng Liang

IPC: C07C227/18 ,  C07C201/08 ,  C07C227/16 ,  C07C227/06

Abstract: 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. The method includes: nitrating phenylacetate to prepare o-nitrophenylacetate (2); hydrogenating o-nitrophenylacetate (2) to prepare o-aminophenylacetate (3); amidating an amino group of o-aminophenylacetate (3) to obtain 2-(2-benzoylaminophenyl) acetate (4); 2-(2-benzoylaminophenyl) acetate (4) reacting with thionyl chloride to prepare a chloroimine intermediate, and then condensing the intermediate of chloroimine with 2,6-dichlorophenol using an inorganic base to prepare (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5); subjecting (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5) to Chapman rearrangement to afford methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6); and hydrolyzing methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6) to provide the target compound as of diclofenac sodium API. The overall yield is up to 67% based on methyl phenylacetate.