WO2018020380A1 - Enzymatic process for the preparation of (r)-3-aminobutan-1-ol, useful in preparation of dolutegravir - Google Patents

Enzymatic process for the preparation of (r)-3-aminobutan-1-ol, useful in preparation of dolutegravir Download PDF

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WO2018020380A1
WO2018020380A1 PCT/IB2017/054435 IB2017054435W WO2018020380A1 WO 2018020380 A1 WO2018020380 A1 WO 2018020380A1 IB 2017054435 W IB2017054435 W IB 2017054435W WO 2018020380 A1 WO2018020380 A1 WO 2018020380A1
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aminobutan
ata
evo
dolutegravir
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Amol Gulab KHATIK
Mofazzal Husain
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Lupin Limited
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    • C—CHEMISTRY; METALLURGY
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    • C12Y—ENZYMES
    • C12Y206/00—Transferases transferring nitrogenous groups (2.6)
    • C12Y206/01—Transaminases (2.6.1)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/001—Amines; Imines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

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  • the present invention provides process for preparation of enantiomerically pure (R)-3- aminobutan-1-ol (I) by treating 4-hydroxybutan-2-one (II) with transaminase enzyme and its use i n the preparation of dolutegravir (III) or its salt thereof.
  • Dolutegravir is an integrase inhibitor. It is used against HIV infections as a single drug or 3a fixed-dose combination with abacavir sulphate and lamivudine under the trade names Tivicay ⁇ andTriumeq ⁇ respectively.
  • dolutegravir as its sodium salt
  • the chemical name for dolutegravir is (4R,12aS)-9- ⁇ [(2,4- difl uoropheny I) methyl] carbamoyl ⁇ -4- methyl -6,8- di oxo-3,4,6,8,12,12a-hexahydro-2H- pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olateand represented by formula (III).
  • Enantiomerically pure compounds play an important role in the pharmaceutical and chemical industry and enantiomerically pure chiral amines are frequently used as , intermediates or synthons for the preparation of various pharmaceutically active. In a great number of applications of enantiomerically pure chiral amines, only one particular optically active form, either the (R) or the (S) enantiomer has the desired physiological activity. Thus, there is a clear need to provide process for the preparation of chiral amines in an optically active form.
  • One such chiral amine, (R)-3-aminobutan-1-ol (I) is used for i3 ⁇ 4 the preparation of dolutegravir (III) or its pharmaceutically acceptable salt
  • the present invention provides commercial process for the preparation of (R)-3- aminobutan-1-ol (I), which is simple and does not involve multiple steps or expensive 3 ⁇ 4 reagents.
  • the present invention provides process for preparation of enantiomerically pure (R)-3- aminobutan-1-ol (I) by treating 4- hydroxy butan-2-one (II) with transaminase enzyme.
  • the present invention further provides use of enantiomerically pure (R)-3-aminobutan-1- , ol (I) in the preparation of dolutegravir (III) or its salt thereof.
  • the present invention provides process for preparation of enantiomerically pure (R)-3-aminobutan-1-ol (I) comprising treating 4-hydroxybutan-2- (II) with R-selective transaminase enzyme in presence of amino donor as shown 2me 1.
  • a mi no donor_ i s used to refer to any ami no aci d or ami ne that wi 11 react with aa transami nase and a ketone, to produce desi red ami ne product and a ketone by product
  • enantiomerically pure_ refers to (R)-3-aminobutan-1-ol with a chi ral purity of greater than 99%, preferably greater than 99.5%, more preferably greater than 99.9%, by H PLC.
  • the transamination reaction is carried out in presence of " Pyridoxal- phosphate (PL P)_ that acts as a coenzyme.
  • PL P Pyridoxal- phosphate
  • the amine group of the amino donor is transferred to the coenzyme to produce a ketone as a by-product, while pyridoxal-5 -phosphate is converted to pyridoxamine phosphate.
  • the transfer of the amine group from pyridoxamine phosphate to the ketone substrate produces a chiral ami ne and regenerates the coenzyme.
  • R-selective transaminase enzyme include, but are not limited to ATA-415, ATA-301, Evo- 1.2.126, Evo - 1.2.131, Evo-1.2.134, Evo-1.2.135, Evo-1.2.137 , ECS-ATA-05, ECS-ATA-02, ECS-ATA-07, ECS-ATA-134 and mixtures thereof;
  • Typical amino donors that can be used with the invention include chiral and achiral amino acids, and chiral and achiral amines.
  • Amino donors that can be used with the invention include, by way of example and not limited to isopropylamine, 1 -phenyl ethanamine, 2- aminobutane, 2-amino-1-butanol, 1-phenyl-2-aminobutane, including salts of the amines. 3 ⁇ 4 More preferably, the amino donor is isopropylamine thereby obtaining acetone as a byproduct.
  • Transamination of the substrates is carried out in a bioreactor using an aliquot of the enzyme with the substrate typically at a defined concentration.
  • T able 1 Performance of T ransami nase enzymes after screeni ng.
  • ECS-ATA-134 100% 0
  • the present invention provides use of enantiomerically pure (R)-3-aminobutan-1-ol (I) in the preparation of dolutegravir (III).
  • the present invention provides preparation of enantiomerically pure (R)-3-aminobutan-1- ol (I) in a single step conversion; the process is simple, industrially viable and 3 ⁇ 4 environment friendly.
  • Buffer preparation 10 ml water, 1.25 ml isopropylami ne, 0.25 gm tri ethanol amine, 4 mg Pyridoxal 5 " -phosphate (PL P) was mixed and pH was adjusted to 7 to 7.5 using 50% hydrochloride solution. Total volume of the solution was made upto 15 ml with distilled , water.
  • Substrate solution preparation 0.132 gm of 4-hydroxy-2-butanone was dissolved in 3 ml of dimethyl sulfoxide.
  • Phosphate buffer preparation (1 M) A solution of 13.6 gm of K H 2 P0 4 in 100 ml water was added to a solution of 17.4 gm of K 2 HP0 4 in 100 ml water. The resultant solution has 3 ⁇ 4 pH 8.00.
  • Substrate sol ution preparation 240 mg 4-Hydroxy butanone was dissolved in 2 ml Dimethyl sulfoxide.

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Abstract

The present invention provides process for preparation of enantiomerically pure (R)-3- aminobutan-1-ol (I) by treating 4-hydroxybutan-2-one (II) with transaminase enzyme and use of enantiomerically pure (R)-3-aminobutan-1-ol (I) in the preparation of dolutegravir or its salt thereof.

Description

ENZYMATIC PROCESS FOR THE PREPARATION OF
(R)-3-AMINOBUTAN-1-OL, USEFUL IN PREPARATION OF DOLUTEGRAVIR
FIELD OF INVENTION
¾ The present invention provides process for preparation of enantiomerically pure (R)-3- aminobutan-1-ol (I) by treating 4-hydroxybutan-2-one (II) with transaminase enzyme and its use i n the preparation of dolutegravir (III) or its salt thereof.
BACKGROUND OF THE INVENTION
Dolutegravir is an integrase inhibitor. It is used against HIV infections as a single drug or 3a fixed-dose combination with abacavir sulphate and lamivudine under the trade names Tivicay÷ andTriumeq÷ respectively. These commercial products contain dolutegravir as its sodium salt The chemical name for dolutegravir is (4R,12aS)-9-{[(2,4- difl uoropheny I) methyl] carbamoyl} -4- methyl -6,8- di oxo-3,4,6,8,12,12a-hexahydro-2H- pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olateand represented by formula (III).
3R
Figure imgf000002_0001
(HI)
Enantiomerically pure compounds play an important role in the pharmaceutical and chemical industry and enantiomerically pure chiral amines are frequently used as , intermediates or synthons for the preparation of various pharmaceutically active. In a great number of applications of enantiomerically pure chiral amines, only one particular optically active form, either the (R) or the (S) enantiomer has the desired physiological activity. Thus, there is a clear need to provide process for the preparation of chiral amines in an optically active form. One such chiral amine, (R)-3-aminobutan-1-ol (I) is used for i¾ the preparation of dolutegravir (III) or its pharmaceutically acceptable salt
Figure imgf000003_0001
Synthetic methods for the preparation of (R)-3-aminobutan-1-ol (I) are reported in the literature. J ournal of Organic Chemistry 1977, 42 (9), 1650-1652, provides process for preparation of (R)-3-aminobutan-1-ol (I); it is a multiple step process and hence ¾ unsuitable for commercial production.
The patent US 8,288,575 discloses a process for the preparation of (R)-3-aminobutan-1-ol (I), wherein methyl (R)-3-aminobutanoate is hydrogenated using ruthenium complex in a solvent. This process involves expensive catalyst like ruthenium making it unviable for commercial scale.
3a Another patent US 9115052 discloses a process for the resolution of (R)-3-aminobutan-1- ol (I) with (S)-mandelic acid and the patent application US 2016/108058 provides resolution of (R)-3-aminobutan-1-ol (I) with tartaric acid.
The present invention provides commercial process for the preparation of (R)-3- aminobutan-1-ol (I), which is simple and does not involve multiple steps or expensive ¾ reagents.
SU M MA RY OF T H E INV E NTIO N
The present invention provides process for preparation of enantiomerically pure (R)-3- aminobutan-1-ol (I) by treating 4- hydroxy butan-2-one (II) with transaminase enzyme.
The present invention further provides use of enantiomerically pure (R)-3-aminobutan-1- , ol (I) in the preparation of dolutegravir (III) or its salt thereof.
DE TAIL E D DE SC R IPT ION O F T H E I NV E NT IO N
In the first embodiment, the present invention provides process for preparation of enantiomerically pure (R)-3-aminobutan-1-ol (I) comprising treating 4-hydroxybutan-2- (II) with R-selective transaminase enzyme in presence of amino donor as shown 2me 1.
Figure imgf000004_0001
4-hydroxybutan-2-one (IT) (R)-3-aminobutan-l-ol (I)
Scheme- 1
The term "Transaminase" also referred as "Amine Transaminase (ATA)_ is used to refer to a polypeptide having an enzymatic capability of transferring an amino group (NH2) to a carbonyl group (C=0) of an acceptor molecule.
T he term "A mi no donor_ i s used to refer to any ami no aci d or ami ne that wi 11 react with aa transami nase and a ketone, to produce desi red ami ne product and a ketone by product
The term "enantiomerically pure_ refers to (R)-3-aminobutan-1-ol with a chi ral purity of greater than 99%, preferably greater than 99.5%, more preferably greater than 99.9%, by H PLC.
The transamination reaction is carried out in presence of "Pyridoxal- phosphate (PL P)_ that acts as a coenzyme. In transamination reactions using transaminase enzymes, the amine group of the amino donor is transferred to the coenzyme to produce a ketone as a by-product, while pyridoxal-5 -phosphate is converted to pyridoxamine phosphate. The transfer of the amine group from pyridoxamine phosphate to the ketone substrate produces a chiral ami ne and regenerates the coenzyme. , R-selective transaminase enzyme include, but are not limited to ATA-415, ATA-301, Evo- 1.2.126, Evo - 1.2.131, Evo-1.2.134, Evo-1.2.135, Evo-1.2.137 , ECS-ATA-05, ECS-ATA-02, ECS-ATA-07, ECS-ATA-134 and mixtures thereof; Typical amino donors that can be used with the invention include chiral and achiral amino acids, and chiral and achiral amines. Amino donors that can be used with the invention include, by way of example and not limited to isopropylamine, 1 -phenyl ethanamine, 2- aminobutane, 2-amino-1-butanol, 1-phenyl-2-aminobutane, including salts of the amines. ¾ More preferably, the amino donor is isopropylamine thereby obtaining acetone as a byproduct.
Transamination of the substrates is carried out in a bioreactor using an aliquot of the enzyme with the substrate typically at a defined concentration. The reaction parameters such as pH = 6-9, temperature = 20 - 40eC, and reaction time = 12-48 hours area maintained at levels that favor optimal biocatalytic activity and stability.
In the present invention various transaminase enzymes for conversion of 4- hydroxy butan- 2-one (II) to (R)-3-aminobutan-1-ol (I) were screened. T he result is summarized i n Table 1.
T able 1 : Performance of T ransami nase enzymes after screeni ng.
Sr. T ransaminase Desired Un desired
No. E nzyme Code (R)-Amine (S)-A mine
1. ATA-415 97.10% 2.9%
2. ATA-301 100 % 0
3. Evo-1.2.126 92.63% 7.37%
4. Evo-1.2.131 84.93% 15.07%
5. Evo-1.2.134 86.49% 13.51%
6. Evo-1.2.135 100 % 0
7. Evo-1.2.137 100 % 0
8. ECS-ATA-05 100 % 0
9. ECS-ATA-02 100% 0
10. ECS-ATA-07 87% 13%
11. ECS-ATA-134 100% 0 In the second embodiment the present invention provides use of enantiomerically pure (R)-3-aminobutan-1-ol (I) in the preparation of dolutegravir (III).
The present invention provides preparation of enantiomerically pure (R)-3-aminobutan-1- ol (I) in a single step conversion; the process is simple, industrially viable and ¾ environment friendly.
Process for preparation of dolutegravir (III) using enantiomerical ly pure (R)-3- aminobutan-1-ol (I) is carried out by methods disclosed in patent US 9242986 and Indian patent appl i cati on 4792/M U M/2015.
The present invention is further illustrated by the following representative examples and 3a does not l imit the scope of the invention. Examples:
The enantiomeric purity was determined by H PLC using the following parameters: Column: Chiralcel OJ -H,5i m; Mobile phase: n-Hexane: Ethanol and T FA (92:08:0.1) v/v ;Flow rate:1.0 ml/min; Detector: UV, 254 nm; Injection V olume: 25 ι L; Run Time :45 Min
¾ Source of E nzymes: Codexis, Evocatal and E nzymicals E xample 1 : Preparation of (R)-3-aminobutan-1-ol (I)
Buffer preparation: 10 ml water, 1.25 ml isopropylami ne, 0.25 gm tri ethanol amine, 4 mg Pyridoxal 5 "-phosphate (PL P) was mixed and pH was adjusted to 7 to 7.5 using 50% hydrochloride solution. Total volume of the solution was made upto 15 ml with distilled , water.
Substrate solution preparation: 0.132 gm of 4-hydroxy-2-butanone was dissolved in 3 ml of dimethyl sulfoxide.
A mixture of 10 mg ATA-301 enzyme, 900 ι L buffer and 100 ι L substrate solution was stirred at 30eC at 900 rotations per minute for 24-48 hours. Sample was analyzed by i¾ H PLC and conversion was obtained with 100% R-isomer. E xample 2: Preparation of (R)-3-aminobutan-1-ol (I)
Phosphate buffer preparation (1 M): A solution of 13.6 gm of K H2P04 in 100 ml water was added to a solution of 17.4 gm of K2HP04 in 100 ml water. The resultant solution has ¾ pH 8.00.
Substrate sol ution preparation: 240 mg 4-Hydroxy butanone was dissolved in 2 ml Dimethyl sulfoxide.
Preparation of (R)-3-ami nobutan-1-ol
A mixture of 18 mg ECS-ATA-134, 150 ι L PL P solution, 150 ι L phosphate buffer, 400a I L secondary butyl amine solution, 100 ι L magnesi um chloride solution, 100 ι L water, 100 I L substrate solution was stirred at 15eC for 24 hours. Sample was analyzed by H PLC and conversion was obtained with 100% R-isomer.
E xample 3: Preparation of (R)-3-aminobutan-1-ol (I)
R
A mixture of 0.9 gm enzyme ECS-ATA-134 and 7.5 ml PL P solution was added to a solution of phosphate buffer (15 ml, of example 2), secondary butyl amine (20 ml) and magnesium chloride (5 ml) fol lowed by addition of a substrate solution (0.6 gm 4- Hydroxy butanone in 5 ml Dimethyl sulfoxide). The reaction mixture was stirred at 15eC , for 24 hours. The reaction mixture was extracted with ethyl acetate and the solvent was removed by disti llation to obtai n (R)-3-aminobutan-1-ol. Y ield: 0.45 gm, 100% R-isomer.

Claims

C LAIMS
1. A process for preparation of enantiomerically pure (R)-3-aminobutan-1-ol (I) comprising treating 4- hydroxy butan-2-one (II) with R-selective transaminase ¾ enzyme i n presence of ami no donor.
Figure imgf000008_0001
(1) (Π)
2. The process according to claim 1, wherein R-selective transaminase enzyme is ATA-415, ATA -301, Evo- 1.2.126, Evo - 1.2.131, Evo-1.2.134, Evo-1.2.135, Evo-1.2.137, E CS-ATA-05, ECS-ATA-02, ECS-ATA-07, ECS-ATA-134 and
3a mixtures.
3. The process according to claim 1, wherein amino donor is an amino acid.
4. The process according to claim 3, wherein amino acid is isopropylamine, 1- phenylethanamine, 2-aminobutane, 2-amino-1-butanol, 1- phenyl -2- ami nobutane and their salts.
¾ 5. A process for preparation of enantiomerically pure (R)-3-aminobutan-1-ol (I) according to claim 1, further comprising treating 4-hydroxybutan-2-one (II) with R-selective transaminase enzyme in presence of amino donor and a coenzyme.
6. T he process accordi ng to clai m 5, wherei n coenzyme is pyri doxal phosphate
7. The process according to claim 1, wherein the H PLC purity of (R)-3-ami nobutan- tft 1 -ol (I) i s greater than 99%. The process according to claim 1, wherein the H PLC purity of (R)-3-ami nobutan- 1-ol (I) is greater than 99.5%.
Use of enantiomerically pure (R)-3-aminobutan-1-ol (I) of claim 1, in the preparation of dolutegravir or its salts.
PCT/IB2017/054435 2016-07-25 2017-07-21 Enzymatic process for the preparation of (r)-3-aminobutan-1-ol, useful in preparation of dolutegravir WO2018020380A1 (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108823179A (en) * 2018-06-30 2018-11-16 浙江工业大学 A kind of transaminase from actinomyces, mutant, recombinant bacterium and application
CN112852895A (en) * 2020-12-01 2021-05-28 中国科学院天津工业生物技术研究所 Method for synthesizing (R) -3-amino-1-butanol by double-enzyme cascade catalysis
WO2023102374A1 (en) 2021-12-03 2023-06-08 Viiv Healthcase Company Process of synthesizing (r)-3-aminobutan-1-ol

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6133018A (en) * 1997-06-02 2000-10-17 Celgro Enzymatic synthesis of chiral amines using -2-amino propane as amine donor
US8288575B2 (en) 2008-09-09 2012-10-16 Takasago International Corporation Alcohol production method by reducing ester of lactone with hydrogen
WO2014128545A2 (en) * 2013-02-19 2014-08-28 Aurobindo Pharma Limited An improved process for the preparation of dolutegravir
US9115052B2 (en) 2009-01-16 2015-08-25 Basf Se Separation of an enantiomer mixture of (R)- and (S)-3-amino-1-butanol
US9242986B2 (en) 2008-12-11 2016-01-26 Shionogi & Co., Ltd. Synthesis of carbamoylpyridone HIV integrase inhibitors and intermediates

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6133018A (en) * 1997-06-02 2000-10-17 Celgro Enzymatic synthesis of chiral amines using -2-amino propane as amine donor
US8288575B2 (en) 2008-09-09 2012-10-16 Takasago International Corporation Alcohol production method by reducing ester of lactone with hydrogen
US9242986B2 (en) 2008-12-11 2016-01-26 Shionogi & Co., Ltd. Synthesis of carbamoylpyridone HIV integrase inhibitors and intermediates
US9115052B2 (en) 2009-01-16 2015-08-25 Basf Se Separation of an enantiomer mixture of (R)- and (S)-3-amino-1-butanol
WO2014128545A2 (en) * 2013-02-19 2014-08-28 Aurobindo Pharma Limited An improved process for the preparation of dolutegravir
US20160108058A1 (en) 2013-02-19 2016-04-21 Aurobindo Pharma Ltd. An improved process for the preparation of Dolutegravir

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
JIANG JINJU ET AL: "Characterization of (R)-selective amine transaminases identified by in silico motif sequence blast", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, SPRINGER, DE, vol. 99, no. 6, 1 October 2014 (2014-10-01), pages 2613 - 2621, XP035459136, ISSN: 0175-7598, [retrieved on 20141001], DOI: 10.1007/S00253-014-6056-1 *
JOURNAL OF ORGANIC CHEMISTRY, vol. 42, no. 9, 1977, pages 1650 - 1652
SRINIVASA RAO YATCHERLA ET AL: "A SIMPLE AND CONVENIENT ROUTE FOR THE SYNTHESIS OF (R)-3-AMINOBUTANOL, AN INTERMEDIATE FOR THE SYNTHESIS OF DOLUTEGRAVIR", ONLINE) CODEN HLEEAI, 1 January 2015 (2015-01-01), pages 2230 - 9632, XP055421951, Retrieved from the Internet <URL:http://www.heteroletters.org/issue25/PDF/Paper-10.pdf> *
TIM BÖRNER ET AL: "A Process Concept for High-Purity Production of Amines by Transaminase-Catalyzed Asymmetric Synthesis: Combining Enzyme Cascade and Membrane-Assisted ISPR", ORGANIC PROCESS RESEARCH AND DEVELOPMENT, vol. 19, no. 7, 17 July 2015 (2015-07-17), US, pages 793 - 799, XP055265098, ISSN: 1083-6160, DOI: 10.1021/acs.oprd.5b00055 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108823179A (en) * 2018-06-30 2018-11-16 浙江工业大学 A kind of transaminase from actinomyces, mutant, recombinant bacterium and application
CN108823179B (en) * 2018-06-30 2020-10-09 浙江工业大学 Transaminase derived from actinomycetes, mutant, recombinant bacterium and application
CN112852895A (en) * 2020-12-01 2021-05-28 中国科学院天津工业生物技术研究所 Method for synthesizing (R) -3-amino-1-butanol by double-enzyme cascade catalysis
CN112852895B (en) * 2020-12-01 2021-11-30 中国科学院天津工业生物技术研究所 Method for synthesizing (R) -3-amino-1-butanol by double-enzyme cascade catalysis
WO2023102374A1 (en) 2021-12-03 2023-06-08 Viiv Healthcase Company Process of synthesizing (r)-3-aminobutan-1-ol

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