公开(公告)号：US09518014B2

公开(公告)日：2016-12-13

申请号：US14415891

申请日：2013-01-29

Applicant: SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES

Inventor： Kuiling Ding ,  Xiaoming Wang ,  Zheng Wang

IPC: C07C229/34 ,  C07D205/08 ,  C07D205/04 ,  C07C67/08 ,  C07C68/00 ,  C07C69/734 ,  C07C69/96 ,  C07C227/32 ,  C07C227/16 ,  C07F9/50 ,  C07F15/00 ,  C07C67/343 ,  C07C67/31 ,  C07C227/18 ,  C07C229/30

CPC classification number: C07D205/04 ,  C07C67/08 ,  C07C67/31 ,  C07C67/343 ,  C07C68/00 ,  C07C69/734 ,  C07C69/96 ,  C07C227/16 ,  C07C227/18 ,  C07C227/32 ,  C07C229/30 ,  C07C229/34 ,  C07C2601/16 ,  C07D205/08 ,  C07F9/5045 ,  C07F15/0033

Abstract: A process for the production of ezetimibe and intermediates used in said process are disclosed. A kind of Morita-Baylis-Hillman adduct can be altered to chiral carboxylic acid derivatives of β-arylamino α-methylene with high activity and selectivity by means of ally lamination reaction, and the above carboxylic acid derivatives of β-arylamino α-methylene can be altered to the chiral intermediates of ezetimibe by means of simple conversion and further synthesized into the chiral drug ezetimibe. The synthesis route introduces chirality through the use of a chiral catalysis method, thereby avoiding the use of the chiral auxiliary oxazolidinone; and the route is economical and eco-friendly.

Abstract translation: 公开了用于生产所述方法中使用的依泽替米贝和中间体的方法。 一种Morita-Baylis-Hillman加合物可以通过烯丙基层压反应改变成具有高活性和选择性的β-芳基氨基α-亚甲基的手性羧酸衍生物，并且上述β-芳基氨基α-亚甲基的羧酸衍生物 通过简单转化将其改变为依泽替米贝的手性中间体，并进一步合成为手性药物依泽替米贝。 合成路线通过使用手性催化方法引入手性，从而避免使用手性辅助恶唑烷酮; 路线经济，环保。

公开(公告)号：US09434665B2

公开(公告)日：2016-09-06

申请号：US14436842

申请日：2013-03-22

Applicant: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

Inventor： Kuiling Ding ,  Zhaobin Han

IPC: C07C29/136 ,  C07F15/00 ,  B01J31/24 ,  B01J31/18 ,  C07F19/00

CPC classification number: C07C29/136 ,  B01J31/189 ,  B01J31/24 ,  B01J31/2476 ,  B01J2231/643 ,  B01J2531/0247 ,  B01J2531/821 ,  C07B2200/05 ,  C07C41/26 ,  C07F15/0046 ,  C07F19/00 ,  Y02P20/52 ,  C07C31/04 ,  C07C31/20 ,  C07C31/202 ,  C07C31/205 ,  C07C31/207 ,  C07C33/26 ,  C07C43/13 ,  C07C43/1782

Abstract: Provided is a method for preparing methanol and diol from cyclic carbonate, comprising: under a hydrogen atmosphere, in an organic solvent, and with the presence of a ruthenium complex (Ru(L)XYY′) and an alkali, conducting a hydrogenation reduction reaction on the cyclic carbonate or polycarbonate to obtain methanol and diol. Also provided is a ruthenium complex prepared from ruthenium and a tridentate amido diphosphine ligand. Also provided is a deuterated methanol and deuterated diol preparation method by substituting the hydrogen and ruthenium complex with deuterium.

Abstract translation: 本发明提供从环状碳酸酯制备甲醇和二醇的方法，包括：在氢气氛下，在有机溶剂中，在钌络合物（Ru（L）XYY'）和碱的存在下，进行氢化还原反应 在环状碳酸酯或聚碳酸酯上得到甲醇和二醇。 还提供了由钌和三齿酰氨基二膦配体制备的钌络合物。 还提供了通过用氘代替氢和钌络合物的氘代甲醇和氘代二醇制备方法。

公开(公告)号：US20220251039A1

公开(公告)日：2022-08-11

申请号：US17451021

申请日：2021-10-15

Applicant: Fudan University ,  Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

Inventor： Yang Wang ,  Mingming Liu ,  Pengfei Zhou ,  Kechang Feng ,  Kuiling Ding ,  Xiaoming Wang

IPC: C07D205/08 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  A61P35/00

Abstract: The present invention relates to the field of synthetic medicinal chemistry and provides a series of novel diaryl-β-lactam compounds having significant anti-tumor activity, and the pharmaceutical use thereof. The present invention also comprises the use of these compounds, pharmaceutical salts, and pharmaceutical composition thereof for preparing a pharmaceutical for the prevention or treatment of tumor-associated disease. The diaryl-β-lactam compounds of the present invention have the following general formula (I).

公开(公告)号：US20150252055A1

公开(公告)日：2015-09-10

申请号：US14415857

申请日：2013-01-29

Applicant: SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES

Inventor： Kuiling Ding ,  Xiaoming Wang ,  Zhaobin Han ,  Xubin Wang ,  Zheng Wang

IPC: C07D493/10 ,  C07D495/20 ,  C07D491/20 ,  C07F9/6561

CPC classification number: C07D493/10 ,  B01J31/2247 ,  B01J31/2409 ,  B01J2231/32 ,  B01J2531/0238 ,  B01J2531/0261 ,  B01J2531/824 ,  C07B53/00 ,  C07C227/32 ,  C07D491/20 ,  C07D493/20 ,  C07D495/20 ,  C07F9/6561 ,  C07F9/65616 ,  C07F15/0033 ,  C07C229/34

Abstract: Disclosed are aromatic spiroketal diphosphine ligands, preparation methods and uses thereof. The ligands have the structure of formula (I), in which R1, R2, R3, R4, R5, R6, R7, R8, X and n are defined as such described in the specification. The aromatic spiroketal diphosphine ligands are prepared from aromatic spiroketal compounds. Also disclosed are the preparation methods of aromatic spiroketal compounds. The preparation methods are simple and can produce racemic or chiral aromatic spiroketal diphosphine ligands. The ligands can be used as catalysts of asymmetrical catalytic reactions having economical practicability and industry application prospect.

Abstract translation: 公开了芳族螺旋二膦配体，其制备方法和用途。 配体具有式（I）的结构，其中R1，R2，R3，R4，R5，R6，R7，R8，X和n如说明书中所述定义。 芳族螺缩酮二膦配体由芳族螺缩酮化合物制备。 还公开了芳族螺缩酮化合物的制备方法。 制备方法简单，可制备外消旋或手性芳香族螺二酮二膦配体。 该配体可用作具有经济实用性和工业应用前景的不对称催化反应催化剂。

公开(公告)号：US11325875B2

公开(公告)日：2022-05-10

申请号：US16060424

申请日：2016-12-12

Applicant: ZHEJIANG JIUZHOU PHARMACEUTICAL CO., LTD. ,  SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES

Inventor： Kuiling Ding ,  Yuxi Cao ,  Zhiyao Zheng ,  Qinglei Chong ,  Zheng Wang

IPC: C07C13/72 ,  B01J31/22 ,  C07C39/17 ,  C07C43/21 ,  C07C43/225 ,  C07F9/6571 ,  C07B53/00 ,  C07C231/12 ,  C07C233/51

Abstract: Chiral spirobiindane skeleton compound and preparation method thereof is disclosed in the present invention. The spirobiindane skeleton compound of the present invention having the structure formula of I or I′; the preparation method for synthesizing the spirobiindane skeleton compound of the present invention comprising the following steps: in the presence of solvent and catalysts, the structure formula compound III reacted through intramolecular Friedel-Crafts reaction to obtain the compound of formula I; the catalyst is a Browsteric acidor Lewis acid. The preparation method of chiral fused spirobiindane skeleton compound of the present invention does not need to adopt chiral starting materials or chiral resolving agents, does not require chiral resolving steps, is simple in method, is simple in post-treatment, and is economic and environment friendly. High product yield, high product optical purity and chemical purity. The catalyst for the asymmetric reaction is obtained from the chiral spirobiindane skeleton ligand of the present invention, under the catalytic reagent of transition metal, the catalyzed hydrogenation reaction can arrive at a remarkable catalytic effect with a product yield of >99%, and a product ee value of up to >99%.

公开(公告)号：US09527862B2

公开(公告)日：2016-12-27

申请号：US14415857

申请日：2013-01-29

Applicant: SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES

Inventor： Kuiling Ding ,  Xiaoming Wang ,  Zhaobin Han ,  Xubin Wang ,  Zheng Wang

IPC: C07D491/20 ,  C07D493/10 ,  C07D493/20 ,  C07F9/6561 ,  B01J31/22 ,  B01J31/24 ,  C07B53/00 ,  C07F15/00 ,  C07C227/32 ,  C07D495/20

CPC classification number: C07D493/10 ,  B01J31/2247 ,  B01J31/2409 ,  B01J2231/32 ,  B01J2531/0238 ,  B01J2531/0261 ,  B01J2531/824 ,  C07B53/00 ,  C07C227/32 ,  C07D491/20 ,  C07D493/20 ,  C07D495/20 ,  C07F9/6561 ,  C07F9/65616 ,  C07F15/0033 ,  C07C229/34

Abstract: Disclosed are aromatic spiroketal diphosphine ligands, preparation methods and uses thereof. The ligands have the structure of formula (I), in which R1, R2, R3, R4, R5, R6, R7, R8, X and n are defined as such described in the specification. The aromatic spiroketal diphosphine ligands are prepared from aromatic spiroketal compounds. Also disclosed are the preparation methods of aromatic spiroketal compounds. The preparation methods are simple and can produce racemic or chiral aromatic spiroketal diphosphine ligands. The ligands can be used as catalysts of asymmetrical catalytic reactions having economical practicability and industry application prospect

Abstract translation: 公开了芳族螺旋二膦配体，其制备方法和用途。 配体具有式（I）的结构，其中R1，R2，R3，R4，R5，R6，R7，R8，X和n如说明书中所述定义。 芳族螺缩酮二膦配体由芳族螺缩酮化合物制备。 还公开了芳族螺缩酮化合物的制备方法。 制备方法简单，可制备外消旋或手性芳香族螺二酮二膦配体。 该配体可用作具有经济实用性和工业应用前景的不对称催化反应催化剂。

公开(公告)号：US20150166479A1

公开(公告)日：2015-06-18

申请号：US14415891

申请日：2013-01-29

Applicant: SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY, CHINESE ACADEMY OF SCIENCES

Inventor： Kuiling Ding ,  Xiaoming Wang ,  Zheng Wang

IPC: C07D205/04 ,  C07C67/31 ,  C07C227/18 ,  C07C229/30 ,  C07C227/16

CPC classification number: C07D205/04 ,  C07C67/08 ,  C07C67/31 ,  C07C67/343 ,  C07C68/00 ,  C07C69/734 ,  C07C69/96 ,  C07C227/16 ,  C07C227/18 ,  C07C227/32 ,  C07C229/30 ,  C07C229/34 ,  C07C2601/16 ,  C07D205/08 ,  C07F9/5045 ,  C07F15/0033

Abstract: A process for the production of ezetimibe and intermediates used in said process are disclosed. A kind of Morita-Baylis-Hillman adduct can be altered to chiral carboxylic acid derivatives of β-arylamino α-methylene with high activity and selectivity by means of ally lamination reaction, and the above carboxylic acid derivatives of β-arylamino α-methylene can be altered to the chiral intermediates of ezetimibe by means of simple conversion and further synthesized into the chiral drug ezetimibe. The synthesis route introduces chirality through the use of a chiral catalysis method, thereby avoiding the use of the chiral auxiliary oxazolidinone; and the route is economical and eco-friendly.

Abstract translation: 公开了用于生产所述方法中使用的依泽替米贝和中间体的方法。 一种Morita-Baylis-Hillman加合物可以通过烯丙基叠层反应改变成具有高活性和选择性的α-芳基氨基-α-亚甲基的手性羧酸衍生物，并且上述α-芳基氨基-α-亚甲基的羧酸衍生物， 亚甲基可以通过简单的转化改变为依泽替米贝的手性中间体，并进一步合成到手性药物依泽麦布中。 合成路线通过使用手性催化方法引入手性，从而避免使用手性辅助恶唑烷酮; 路线经济，环保。