公开(公告)号：US20230234911A1

公开(公告)日：2023-07-27

申请号：US18172414

申请日：2023-02-22

Applicant: Fudan University

Inventor： Fener CHEN ,  Dang CHENG ,  Lulu WANG ,  Ge MENG ,  Yingtang NING ,  Zedu HUANG

IPC: C07C227/18 ,  B01J21/02

CPC classification number: C07C227/18 ,  B01J21/02

Abstract: 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.

公开(公告)号：US20220090151A1

公开(公告)日：2022-03-24

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

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：US20180339974A1

公开(公告)日：2018-11-29

申请号：US15871049

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener CHEN ,  Guanxin HUANG ,  Ge MENG ,  Minjie LIU ,  Yan WU ,  Dang CHENG ,  Zedu HUANG ,  Haihui PENG ,  Fangjun XIONG

IPC: C07D319/06 ,  C07B41/12 ,  C07B47/00

CPC classification number: C07D319/06 ,  C07B41/12 ,  C07B47/00

Abstract: The present disclosure belongs to the technical field of organic synthesis and particularly relates to a preparation method for 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate. The 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is a key chiral intermediate for preparation of statin antilipemic agents. In the present disclosure, the 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is obtained by bromination and cyclization of 3-((substituted oxycarbonyl)oxy)-5-hexenoate as raw material with hypochlorite and bromide in an organic solvent in the presence of CO2. The method of the present disclosure has the advantages of readily available raw material, mild reaction conditions, easy operation, low cost, excellent atomic economy and less by-products, and is applicable to industrial production.

公开(公告)号：US20250042892A1

公开(公告)日：2025-02-06

申请号：US18807978

申请日：2024-08-18

Applicant: Fudan University

Inventor： Ge MENG ,  Weijuan GE ,  Jing TONG ,  Yanan CHENG ,  Huiling CAO

IPC: C07D417/12 ,  A61K31/427

Abstract: A series of 2-(5-substituted-indolone-3-yl-hydrozono)-3-substituted-arylidene-1,3-thiazolidinone derivatives represented by where R1 is Cl, F, Br or CH3, and R2 is 4-F, 3-Cl, 3-CF3 or 4-C(CH3)3. A pharmaceutical composition including such 2-(5-substituted-indolone-3-yl-hydrozono)-3-substituted-arylidene-1,3-thiazolidinone derivative, or a pharmaceutically-acceptable salt thereof is provided. A preparation method of such derivative and an application of such derivative as a lead compound in the preparation of PARP14 inhibitors are further provided.

公开(公告)号：US20230192595A1

公开(公告)日：2023-06-22

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-indo1-2-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：US20200055811A1

公开(公告)日：2020-02-20

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 ,  C07C227/06 ,  C07C227/16

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.

公开(公告)号：US20180340196A1

公开(公告)日：2018-11-29

申请号：US15871039

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener CHEN ,  Zedu HUANG ,  Ge MENG ,  Minjie LIU ,  Zhining LI ,  Zexu WANG ,  Haihui PENG ,  Fangjun XIONG ,  Yan WU ,  Yuan TAO

IPC: C12P7/62 ,  C07C69/732 ,  C07C67/28 ,  C12N9/04

CPC classification number: C12P7/62 ,  C07C67/28 ,  C07C69/732 ,  C12N9/0006 ,  C12Y101/0108 ,  G01N30/7206 ,  G01N30/88 ,  G01N2030/025

Abstract: The present disclosure relates to the technical field of biochemical engineering and particularly discloses a preparation method for (R)-3-hydroxyl-5-hexenoate. In the method of the present disclosure, the (R)-3-hydroxyl-5-hexenoate is prepared by catalytic reduction of 3-carbonyl-5-hexenoate by ketoreductase with 3-carbonyl-5-hexenoate as the substrate. The amino acid sequence of ketoreductase is shown in SEQ ID NO.1. In the present disclosure, the (R)-3-hydroxyl-5-hexenoate having a very high chiral purity is obtained by asymmetric reduction by ketoreductase as the biocatalyst. The present disclosure has the advantages of easy operation, mild reaction conditions, high reaction yield and good practical industrial application value.