公开(公告)号：US11834425B2

公开(公告)日：2023-12-05

申请号：US18166478

申请日：2023-02-09

Applicant: Fudan University

Inventor： Fener Chen ,  Meifen Jiang ,  Minjie Liu ,  Yingqi Xia ,  Weijian Li

IPC: C07D279/06

CPC classification number: C07D279/06

Abstract: A full continuous-flow preparation method of vitamin B1 includes: (S1) feeding 3-chloro-4-oxopentyl acetate, 2-methyl-4-amino-5-(aminomethyl) pyrimidine and carbon disulfide to a first continuous-flow reactor for addition; (S2) allowing the reaction mixture to flow into a first continuous filtration and reaction device to collect a filter cake; subjecting the filter cake and hydrochloric acid solution to cyclization; transporting the reaction mixture and an aqueous inorganic base solution to a micromixer and a second continuous-flow reactor for hydrolysis to obtain thiothiamine; (S3) transporting the thiothiamine to a third continuous-flow reactor with hydrogen peroxide for oxidation to obtain thiamine sulfate; and (S4) allowing the thiamine sulfate to enter a second continuous filtration and reaction device for filtration to collect a filter cake; and subjecting the filter cake to reaction with organic hydrochloric acid solution followed by filtration and drying to obtain vitamin B1.

公开(公告)号：US11708363B2

公开(公告)日：2023-07-25

申请号：US17488276

申请日：2021-09-28

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Minjie Liu ,  Zedu Huang ,  Yuan Tao ,  Jiaqi Wang

IPC: C07D417/12

CPC classification number: C07D417/12

Abstract: 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.

公开(公告)号：US11618727B2

公开(公告)日：2023-04-04

申请号：US17384747

申请日：2021-07-24

Applicant: Fudan University

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

IPC: C07C67/31 ,  B01J19/00

Abstract: This disclosure relates to organic synthesis, and more particularly to a method for preparing 3-chloro-4-oxopentyl acetate using a fully continuous-flow micro-reaction system. In this method, chlorine and an acetylbutyrolactone-containing liquid are simultaneously transported to a first micro-channel reactor for continuous chlorination to obtain α-acetyl-α-chloro-γ-butyrolactone. The reaction mixture is simultaneously transported to a micro-mixer and a second micro-channel reactor together with a mixed solution of glacial acetic acid, hydrochloric acid and water, and the continuous acylation is carried out to obtain 3-chloro-4-oxopentyl acetate. After quenched with a quenching agent, the reaction mixture was subjected to extraction and separation to obtain the 3-chloro-4-oxopentyl acetate.

公开(公告)号：US11555008B2

公开(公告)日：2023-01-17

申请号：US17123098

申请日：2020-12-15

Applicant: Fudan University

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

IPC: B01J19/00 ,  C07C227/04 ,  C07C229/22

Abstract: 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.

公开(公告)号：US11299451B2

公开(公告)日：2022-04-12

申请号：US16953317

申请日：2020-11-19

Applicant: Fudan University

Inventor： Fener Chen ,  Dang Cheng ,  Zedu Huang ,  Zhining Li ,  Meifen Jiang ,  Yuan Tao

IPC: C07C209/62 ,  C07C17/013 ,  C07C29/38

Abstract: 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).

公开(公告)号：US10526622B2

公开(公告)日：2020-01-07

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 ,  C12N9/04 ,  C07C67/28 ,  G01N30/02

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.

公开(公告)号：US10316012B1

公开(公告)日：2019-06-11

申请号：US16246531

申请日：2019-01-13

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Haihui Peng ,  Sha Hu ,  Ge Meng ,  Yan Wu ,  Dang Cheng ,  Zedu Huang ,  Guanfeng Liang

IPC: C07D307/93

Abstract: Disclosed is a method of synthesizing a series of compounds with the structure of (1S, 5R)-lactone. In the method, under the catalysis of a chiral phosphonic acid, substituted bicyclo[3.2.0]-hept-2-en-6-one (II) as a substrate is reacted with hydrogen peroxide for enantioselective Baeyer-Villiger oxidation to produce a chiral lactone (I). This method involves mild reaction conditions, simple operation, quantitatively recyclable catalyst and high reaction selectivity and stereoselectivity, which is suitable for industrial production.

公开(公告)号：US20150376199A1

公开(公告)日：2015-12-31

申请号：US14766122

申请日：2014-01-10

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Qiuqin He ,  Fangjun Xiong ,  Wenxue Chen ,  Xinlong Wang

IPC: C07D491/147

CPC classification number: C07D491/147

Abstract: The invention belongs to the technical field of organic chemistry, in particular being a method for preparing (+)-tricyclic hydroxyl lactone. The preparation of the (+)-tricyclic hydroxyl lactone compound in the prior art has lengthy steps, low stereoselectivity and high costs. The (+)-tricyclic hydroxyl lactone of the invention is obtained by an asymmetric oxidation reaction of prochiral tricyclic lactones in an organic solvent with an optically active Davis oxidant in the presence of an organic base. The method of the invention uses easily available raw materials, has low costs, good selectivity, and is suitable for large-scale preparation.

Abstract translation: 本发明属于有机化学技术领域，特别是制备（+） - 三环羟基内酯的方法。 现有技术中（+） - 三环羟基内酯化合物的制备具有漫长的步骤，低立体选择性和高成本。 本发明的（+） - 三环羟基内酯通过在有机溶剂中的前手性三环内酯与光学活性的戴维斯氧化剂在有机碱的存在下的不对称氧化反应获得。 本发明的方法使用容易获得的原料，成本低，选择性好，适用于大规模制备。

公开(公告)号：US12281348B2

公开(公告)日：2025-04-22

申请号：US17516894

申请日：2021-11-02

Applicant: Fudan University

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

IPC: C12M1/00 ,  C12M1/02 ,  C12M1/34 ,  C12M1/36 ,  C12P7/625

Abstract: This application relates to organic synthesis, and more particularly to a method for the continuous flow synthesis of (R)-4-halo-3-hydroxy-butyrate using a micro-reaction system. This application performs an enzymatic asymmetric reduction of a substrate solution containing halogenated acetoacetate and a biocatalyst solution in the micro-reaction system composed of a micro-mixer, a micro-channel reactor, and a pH regulator to obtain the (R)-4-halo-3-hydroxy-butyrate. Compared to the prior art, the reaction time of the method is only a few minutes, the yield of the product (R)-4-halo-3-hydroxy-butyrate is greater than 95%, the reaction process is continuous, the degree of automation is high, the efficiency is high, and the process is simple to operate and easy to be used in industrialized production.

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.