公开(公告)号：US20220017508A1

公开(公告)日：2022-01-20

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

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-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.

公开(公告)号：US20210394141A1

公开(公告)日：2021-12-23

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: B01F15/00 ,  B01F13/00

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：US20230183260A1

公开(公告)日：2023-06-15

申请号：US18166906

申请日：2023-02-09

Applicant: Fudan University

Inventor： Fener CHEN ,  Dang CHENG ,  Jiale WU ,  Meifen JIANG ,  Li WAN ,  Jiaqi WANG

IPC: C07D495/04 ,  B01J19/00

CPC classification number: C07D495/04 ,  B01J19/0093 ,  B01J2219/00867 ,  B01J2219/00033

Abstract: A full continuous-flow preparation method of (+)-biotin, including: subjecting a cyclic anhydride and a chiral biphenyl propylene glycol to asymmetric ring-opening reaction to produce a first intermediate, which undergoes selective reduction with a borohydride and cyclization with an inorganic mineral acid to produce (3aS, 6aR)-lactone; subjecting the (3aS, 6aR)-lactone and a sulfenylating reagent to sulfenylation to produce (3aS, 6aR)-thiolactone, which undergoes Fukuyama coupling with a zinc reagent in the presence of a palladium catalyst and elimination reaction in the presence of an inorganic mineral acid to produce an alkenyl valerate compound; subjecting the alkenyl valerate compound to reduction in the presence of a Pd/C catalyst to produce a valerate ester, which undergoes hydrolysis to produce a valeric acid salt; and subjecting the valeric acid salt to debenzylation in the presence of an inorganic mineral acid to produce the target product (+)-biotin.

公开(公告)号：US20210380524A1

公开(公告)日：2021-12-09

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: C07C227/04 ,  B01J19/00

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：US20210087595A1

公开(公告)日：2021-03-25

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

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：US20210355516A1

公开(公告)日：2021-11-18

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 ,  C12N9/02 ,  C12N1/20 ,  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.