公开(公告)号：US6077955A

公开(公告)日：2000-06-20

申请号：US108728

申请日：1998-07-01

Applicant: Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

Inventor： Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

IPC: C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D211/76 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/00 ,  C12P17/10 ,  C07D211/60 ,  C07D207/00

CPC classification number: C07D211/76 ,  C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/002 ,  C12P13/02 ,  C12P17/10 ,  C12R1/01 ,  Y02P20/52

Abstract: A process for the preparation of five-membered or six-membered ring lactams from aliphatic .alpha.,.omega.-dinitriles has been developed. In the process an aliphatic .alpha.,.omega.-dinitrile is first converted to an ammonium salt of an .omega.-nitrilecarboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities. The ammonium salt of the .omega.-nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate .omega.-nitrilecarboxylic acid or .omega.-aminocarboxylic acid. When the aliphatic .alpha.,.omega.-dinitrile is also unsymmetrically substituted at the .alpha.-carbon atom, the nitrilase produces the .omega.-nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the .omega.-nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.

Abstract translation: 已经开发了从脂肪族α，ω-二腈制备五元或六元环内酰胺的方法。 在该方法中，使用具有脂族腈水解酶（EC 3.5.5.7）活性的催化剂或腈水合酶（EC 4.2）的组合，首先将脂族α，ω-二腈转化为ω-二硝基甲酸的铵盐 .1.84）和酰胺酶（EC 3.5.1.4）活性。 然后通过在水溶液中氢化将ω-二硝基羧酸的铵盐直接转化成相应的内酰胺，而不分离中间体ω-二硝基甲酸或ω-氨基羧酸。 当脂肪族α，ω-二腈在α-碳原子处也不对称取代时，腈水解酶产生由ω-腈基水解产生的ω-亚硝基羧酸铵盐，其具有大于98％的区域选择性，从而仅产生 在随后氢化期间两种可能的内酰胺产物。 还提供了在破坏不期望的活性的同时选择期望的区域选择性腈水解酶或腈水合酶活性的热处理方法。

公开(公告)号：US5908954A

公开(公告)日：1999-06-01

申请号：US108445

申请日：1998-07-01

Applicant: Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

Inventor： Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

IPC: C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D211/76 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/00 ,  C12P17/10 ,  C07C255/03 ,  C12P17/12

CPC classification number: C07D211/76 ,  C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/002 ,  C12P13/02 ,  C12P17/10 ,  C12R1/01 ,  Y02P20/52

Abstract: A process for the preparation of five-membered or six-membered ring lactams from aliphatic .alpha.,.omega.-dinitriles has been developed. In the process an aliphatic .alpha.,.omega.-dinitrile is first converted to an ammonium salt of an .omega.-nitrile-carboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and arnidase (EC 3.5.1.4) activities. The ammonium salt of the .omega.-nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate .omega.-nitrilecarboxylic acid or .omega.-aminocarboxylic acid. When the aliphatic .alpha.,.omega.-dinitrile is also unsymmetrically substituted at the .alpha.-carbon atom, the nitrilase produces the .omega.-nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the .omega.-nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.

Abstract translation: 已经开发了从脂肪族α，ω-二腈制备五元或六元环内酰胺的方法。 在该方法中，首先使用具有脂族腈水解酶（EC 3.5.5.7）活性的催化剂或腈水合酶的组合（在水溶液中将ω-腈 - 羧酸的铵盐转化为ω-腈 - 羧酸的铵盐， EC 4.2.1.84）和arnidase（EC 3.5.1.4）活动。 然后通过在水溶液中氢化将ω-二硝基羧酸的铵盐直接转化成相应的内酰胺，而不分离中间体ω-二硝基甲酸或ω-氨基羧酸。 当脂肪族α，ω-二腈在α-碳原子处也不对称取代时，腈水解酶产生由ω-腈基水解产生的ω-亚硝基羧酸铵盐，其具有大于98％的区域选择性，从而仅产生 在随后氢化期间两种可能的内酰胺产物。 还提供了在破坏不期望的活性的同时选择期望的区域选择性腈水解酶或腈水合酶活性的热处理方法。

公开(公告)号：US5466801A

公开(公告)日：1995-11-14

申请号：US110602

申请日：1993-08-26

Applicant: Charles E. Nakamura ,  Robert Di Cosimo ,  John R. Moran

Inventor： Charles E. Nakamura ,  Robert Di Cosimo ,  John R. Moran

IPC: C07D265/32

CPC classification number: C07D265/32

Abstract: A process for the preparation of 3- and/or 6-substituted 2,5-morpholinediones is disclosed. Such morpholinediones are useful as precursors for the preparation of depsipeptide polymers and copolymers.

Abstract translation: 公开了制备3-和/或6-取代的2,5-吗啉二酮的方法。 这种吗啉化物可用作制备去肽肽聚合物和共聚物的前体。

公开(公告)号：US5936114A

公开(公告)日：1999-08-10

申请号：US108631

申请日：1998-07-01

Applicant: Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

Inventor： Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

IPC: C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D211/76 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/00 ,  C12P17/10 ,  C07C255/29

CPC classification number: C07D211/76 ,  C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/002 ,  C12P13/02 ,  C12P17/10 ,  C12R1/01 ,  Y02P20/52

Abstract: A process for the preparation of five-membered or six-membered ring lactams from aliphatic .alpha.,.omega.-dinitriles has been developed. In the process an aliphatic .alpha.,.omega.-dinitrile is first converted to an ammonium salt of an .omega.-nitrilecarboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities. The ammonium salt of the .omega.-nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate .omega.-nitrilecarboxylic acid or .omega.-aminocarboxylic acid. When the aliphatic .alpha.,.omega.-dinitrile is also unsymmetrically substituted at the .alpha.-carbon atom, the nitrilase produces the .omega.-nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the .omega.-nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.

Abstract translation: 已经开发了从脂肪族α，ω-二腈制备五元或六元环内酰胺的方法。 在该方法中，使用具有脂族腈水解酶（EC 3.5.5.7）活性的催化剂或腈水合酶（EC 4.2）的组合，首先将脂族α，ω-二腈转化为ω-二硝基甲酸的铵盐 .1.84）和酰胺酶（EC 3.5.1.4）活性。 然后通过在水溶液中氢化将ω-二硝基羧酸的铵盐直接转化成相应的内酰胺，而不分离中间体ω-二硝基甲酸或ω-氨基羧酸。 当脂肪族α，ω-二腈在α-碳原子处也不对称取代时，腈水解酶产生由ω-腈基水解产生的ω-亚硝基羧酸铵盐，其具有大于98％的区域选择性，从而仅产生 在随后氢化期间两种可能的内酰胺产物。 还提供了在破坏不期望的活性的同时选择期望的区域选择性腈水解酶或腈水合酶活性的热处理方法。

公开(公告)号：US5326887A

公开(公告)日：1994-07-05

申请号：US836228

申请日：1992-02-14

Applicant: Robert Di Cosimo ,  John R. Moran ,  Charles E. Nakamura

Inventor： Robert Di Cosimo ,  John R. Moran ,  Charles E. Nakamura

IPC: C07D319/12 ,  C07D323/04

CPC classification number: C07D319/12

Abstract: This invention relates to a process for preparing 1,4-dioxane-2,5-diones comprising reacting an .alpha.-hydroxy acid oligomer or an ester of an .alpha.-hydroxy acid oligomer over a fixed bed catalyst system.

Abstract translation: 本发明涉及一种制备1,4-二恶烷-2,5-二酮的方法，包括使α-羟基酸低聚物或α-羟基酸低聚物的酯在固定床催化剂体系上反应。

公开(公告)号：US6066490A

公开(公告)日：2000-05-23

申请号：US987938

申请日：1997-12-10

Applicant: Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

Inventor： Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

IPC: C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D211/76 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/00 ,  C12P17/10 ,  C12N1/12

CPC classification number: C07D211/76 ,  C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/002 ,  C12P13/02 ,  C12P17/10 ,  C12R1/01 ,  Y02P20/52

Abstract: A process for the preparation of five-membered or six-membered ring lactams from aliphatic .alpha.,.omega.-dinitriles has been developed. In the process an aliphatic .alpha.,.omega.-dinitrile is first converted to an ammonium salt of an .omega.-nitrilecarboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities. The ammonium salt of the .omega.-nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate .omega.-nitrilecarboxylic acid or .omega.-aminocarboxylic acid. When the aliphatic .alpha.,.omega.-dinitrile is also unsymmetrically substituted at the .alpha.-carbon atom, the nitrilase produces the .omega.-nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the .omega.-nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.

Abstract translation: 已经开发了从脂肪族α，ω-二腈制备五元或六元环内酰胺的方法。 在该方法中，使用具有脂族腈水解酶（EC 3.5.5.7）活性的催化剂或腈水合酶（EC 4.2）的组合，首先将脂族α，ω-二腈转化为ω-二硝基甲酸的铵盐 .1.84）和酰胺酶（EC 3.5.1.4）活性。 然后通过在水溶液中氢化将ω-二硝基羧酸的铵盐直接转化成相应的内酰胺，而不分离中间体ω-二硝基甲酸或ω-氨基羧酸。 当脂肪族α，ω-二腈在α-碳原子处也不对称取代时，腈水解酶产生由ω-腈基水解产生的ω-亚硝基羧酸铵盐，其具有大于98％的区域选择性，从而仅产生 在随后氢化期间两种可能的内酰胺产物。 还提供了在破坏不期望的活性的同时选择期望的区域选择性腈水解酶或腈水合酶活性的热处理方法。

公开(公告)号：US06979720B2

公开(公告)日：2005-12-27

申请号：US10426600

申请日：2003-04-30

Applicant: Edward G. Brugel ,  Robert Di Cosimo

Inventor： Edward G. Brugel ,  Robert Di Cosimo

IPC: C12P7/62 ,  C12P17/02 ,  C12P17/08 ,  C08G63/78 ,  C08G6/00

CPC classification number: C12P17/02 ,  C12P17/08

Abstract: Enzymes which are capable of catalyzing esterifications and/or transesterifications such as selected lipases and esterases can, under specified conditions, convert certain lower linear oligomers of polyesters to their cyclic ester oligomers in quantities greater than would be predicted by thermodynamic calculation or prior art methods. The cyclic ester oligomers are useful for the production of higher molecular weight linear polyesters.

Abstract translation: 能够催化酯化和/或酯交换如选择的脂肪酶和酯酶的酶可以在规定的条件下将聚酯的某些低级线性低聚物转化成其环状酯低聚物，其数量大于通过热力学计算或现有技术方法预测的量。 环酯低聚物可用于生产较高分子量的线性聚酯。

公开(公告)号：US5922589A

公开(公告)日：1999-07-13

申请号：US108729

申请日：1998-07-01

Applicant: Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

Inventor： Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

IPC: C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D211/76 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/00 ,  C12P17/10 ,  C12N1/20 ,  C12P17/12

CPC classification number: C07D211/76 ,  C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/002 ,  C12P13/02 ,  C12P17/10 ,  C12R1/01 ,  Y02P20/52

Abstract: A process for the preparation of five-membered or six-membered ring lactams from aliphatic .alpha., .omega.-dinitriles has been developed. In the process an aliphatic .alpha.,.omega.-dinitrile is first converted to an ammonium salt of an .omega.-nitrilecarboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities. The ammonium salt of the .omega.-nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate .omega.-nitrilecarboxylic acid or .omega.-aminocarboxylic acid. When the aliphatic .alpha.,.omega.-dinitrile is also unsymmetrically substituted at the .alpha.-carbon atom, the nitrilase produces the .omega.-nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the .omega.-nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.

Abstract translation: 已经开发了从脂肪族α，ω-二腈制备五元或六元环内酰胺的方法。 在该方法中，使用具有脂族腈水解酶（EC 3.5.5.7）活性的催化剂或腈水合酶（EC 4.2）的组合，首先将脂族α，ω-二腈转化为ω-二硝基甲酸的铵盐 .1.84）和酰胺酶（EC 3.5.1.4）活性。 然后通过在水溶液中氢化将ω-二硝基羧酸的铵盐直接转化成相应的内酰胺，而不分离中间体ω-二硝基甲酸或ω-氨基羧酸。 当脂肪族α，ω-二腈在α-碳原子处也不对称取代时，腈水解酶产生由ω-腈基水解产生的ω-亚硝基羧酸铵盐，其具有大于98％的区域选择性，从而仅产生 在随后氢化期间两种可能的内酰胺产物。 还提供了在破坏不期望的活性的同时选择期望的区域选择性腈水解酶或腈水合酶活性的热处理方法。

公开(公告)号：US5858736A

公开(公告)日：1999-01-12

申请号：US650073

申请日：1996-05-17

Applicant: Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

Inventor： Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

IPC: C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D211/76 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/00 ,  C12P17/10 ,  C12P17/12

CPC classification number: C07D211/76 ,  C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/002 ,  C12P13/02 ,  C12P17/10 ,  C12R1/01 ,  Y02P20/52

Abstract: A process for the preparation of five-membered or six-membered ring lactams from aliphatic .alpha.,.omega.-dinitriles has been developed. In the process an aliphatic .alpha.,.omega.-dinitrile is first converted to an ammonium salt of an .omega.-nitrilecarboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities. The aimnonium salt of the .omega.-nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate .omega.-nitrilecarboxylic acid or .omega.-monocarboxylic acid. When the aliphatic .alpha.,.omega.-dinitrile is also unsymmetrically substituted at the .alpha.-carbon atom, the nitrilase produces the .omega.-nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the .omega.-nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.

Abstract translation: 已经开发了从脂肪族α，ω-二腈制备五元或六元环内酰胺的方法。 在该方法中，使用具有脂族腈水解酶（EC 3.5.5.7）活性的催化剂或腈水合酶（EC 4.2）的组合，首先将脂族α，ω-二腈转化为ω-二硝基甲酸的铵盐 .1.84）和酰胺酶（EC 3.5.1.4）活性。 然后通过在水溶液中氢化将ω-二硝基甲酸的目的盐直接转化成相应的内酰胺，而不分离中间体ω-二硝基甲酸或ω-单羧酸。 当脂肪族α，ω-二腈在α-碳原子处也不对称取代时，腈水解酶产生由ω-腈基水解产生的ω-亚硝基羧酸铵盐，其具有大于98％的区域选择性，从而仅产生 在随后氢化期间两种可能的内酰胺产物。 还提供了在破坏不期望的活性的同时选择期望的区域选择性腈水解酶或腈水合酶活性的热处理方法。

公开(公告)号：US5814508A

公开(公告)日：1998-09-29

申请号：US910260

申请日：1997-08-13

Applicant: Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

Inventor： Robert Di Cosimo ,  Robert Donald Fallon ,  John Edward Gavagan ,  Frank Edward Herkes

IPC: C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D211/76 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/00 ,  C12P17/10 ,  C12P17/12

CPC classification number: C07D211/76 ,  C07C255/19 ,  C07C255/23 ,  C07D201/08 ,  C07D207/26 ,  C07D223/10 ,  C12N9/78 ,  C12N9/88 ,  C12P13/002 ,  C12P13/02 ,  C12P17/10 ,  C12R1/01 ,  Y02P20/52

Abstract: A process for the preparation of five-membered or six-membered ring lactams from aliphatic .alpha.,.omega.-dinitriles has been developed. In the process an aliphatic .alpha.,.omega.-dinitrile is first converted to an ammonium salt of an .omega.-nitrile-carboxylic acid in aqueous solution using a catalyst having an aliphatic nitrilase (EC 3.5.5.7) activity, or a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) activities. The ammonium salt of the .omega.-nitrilecarboxylic acid is then converted directly to the corresponding lactam by hydrogenation in aqueous solution, without isolation of the intermediate .omega.-nitrilecarboxylic acid or .omega.-aminocarboxylic acid. When the aliphatic .alpha.,.omega.-dinitrile is also unsymmetrically substituted at the .alpha.-carbon atom, the nitrilase produces the .omega.-nitrilecarboxylic acid ammonium salt resulting from hydrolysis of the .omega.-nitrile group with greater than 98% regioselectivity, thereby producing only one of the two possible lactam products during the subsequent hydrogenation. A heat-treatment process to select for desirable regioselective nitrilase or nitrile hydratase activities while destroying undesirable activities is also provided.

Abstract translation: 已经开发了从脂肪族α，ω-二腈制备五元或六元环内酰胺的方法。 在该方法中，首先使用具有脂族腈水解酶（EC 3.5.5.7）活性的催化剂或腈水合酶的组合（在水溶液中将ω-腈 - 羧酸的铵盐转化为ω-腈 - 羧酸的铵盐， EC 4.2.1.84）和酰胺酶（EC 3.5.1.4）活动。 然后通过在水溶液中氢化将ω-二硝基羧酸的铵盐直接转化成相应的内酰胺，而不分离中间体ω-二硝基甲酸或ω-氨基羧酸。 当脂肪族α，ω-二腈在α-碳原子处也不对称取代时，腈水解酶产生由ω-腈基水解产生的ω-亚硝基羧酸铵盐，其具有大于98％的区域选择性，从而仅产生 在随后氢化期间两种可能的内酰胺产物。 还提供了在破坏不期望的活性的同时选择期望的区域选择性腈水解酶或腈水合酶活性的热处理方法。