公开(公告)号：US11913055B2

公开(公告)日：2024-02-27

申请号：US17504858

申请日：2021-10-19

Applicant: Fudan University

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

IPC: C12P7/42 ,  C12P7/62 ,  C12N9/04 ,  C12M3/06 ,  C12N11/084 ,  C12N11/089 ,  C12M1/40 ,  C12M1/00

CPC classification number: C12P7/62 ,  C12M21/18 ,  C12M23/16 ,  C12M29/00 ,  C12N11/084 ,  C12N11/089 ,  C12Y101/0108 ,  C12Y101/01184

Abstract: 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.

公开(公告)号：US11905229B2

公开(公告)日：2024-02-20

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：US10961515B1

公开(公告)日：2021-03-30

申请号：US16904450

申请日：2020-06-17

Applicant: Fudan University

Inventor： Fener Chen ,  Zedu Huang ,  Zexu Wang ,  Minjie Liu

IPC: C12N9/04 ,  C12N1/20 ,  C12N15/52 ,  C12N15/70 ,  C12N15/74 ,  C12P7/62

Abstract: 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.

公开(公告)号：US10214506B2

公开(公告)日：2019-02-26

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 ,  C07B47/00 ,  C07B41/12

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.