US20030124693A1 - Enzymatic conversion of epoxides - Google Patents

Enzymatic conversion of epoxides Download PDF

Info

Publication number
US20030124693A1
US20030124693A1 US10/302,788 US30278802A US2003124693A1 US 20030124693 A1 US20030124693 A1 US 20030124693A1 US 30278802 A US30278802 A US 30278802A US 2003124693 A1 US2003124693 A1 US 2003124693A1
Authority
US
United States
Prior art keywords
process according
epoxide
groups
group
chosen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/302,788
Other languages
English (en)
Inventor
Jeffrey Lutje Spelberg
Dick Janssen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rijksuniversiteit Groningen
Codexis Inc
Original Assignee
Rijksuniversiteit Groningen
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=8171560&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20030124693(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Rijksuniversiteit Groningen filed Critical Rijksuniversiteit Groningen
Assigned to RIJKSUNIVERSITEIT GRONINGEN reassignment RIJKSUNIVERSITEIT GRONINGEN ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: JANSSEN, DICK BAREND, SPELBERG, JEFFREY HARALD LUTJE
Assigned to ENZIS PATENT B.V. reassignment ENZIS PATENT B.V. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GRONINGEN, RIJKSUNIVERSITEIT
Publication of US20030124693A1 publication Critical patent/US20030124693A1/en
Assigned to CODEXIS INC. reassignment CODEXIS INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ENZIS PATENT B.V.
Priority to US11/833,933 priority Critical patent/US7695942B2/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture

Definitions

  • the invention relates to a process for converting an epoxide to an alcohol. More specifically, the invention relates to an enzymatic process for converting an epoxide to an alcohol by nucleophilic substitution.
  • a reaction wherein an epoxide is converted to an alcohol by nucleophilic substitution may be depicted as follows:
  • R may represent a wide range of groups, such as various substituted or unsubstituted alkyl groups, whereas X represents a nucleophile.
  • the product of this conversion may be a very useful building block in the preparation of various fine chemicals, such as certain pharmaceutical products.
  • the reaction may produce two different enantiomers. As the products are often used for applications wherein enantiomeric purity is of great importance, many attempts to find enantioselective ways of carrying out this reaction have been reported.
  • An example of such a reaction is the enantioselective ring opening of an epoxide by an azide anion (N 3 ⁇ ), which may be referred to as an azidolysis.
  • the product of the reaction an optically active azido alcohol is a precursor for biologically active pharmaceuticals such as amino alcohols.
  • a highly enantioselective azidolysis of meso-epoxides and various terminal epoxides using chiral salen complexes has been described by the group of Jacobsen (Martinez et al., J. Am. Chem. Soc., 1995, 117, 5897; Farrow et al., J. Am. Chem.
  • a halohydrin dehalogenase (also referred to as halohydrin hydrogen-halide-lyase, halohydrin epoxidase or haloalcohol dehalogenase) catalyzes the ring-closure of a halohydrin to an epoxide.
  • a halohydrin dehalogenase may also catalyze the reverse reaction. The equilibrium of both reactions may be depicted as follows:
  • R may be chosen from a wide range of groups, such as various substituted or unsubstituted aryl or alkyl groups, and wherein X represents a halogen such as bromide, chloride or iodide.
  • reactions catalyzed by use of enzymes involve the use of less (organic) solvents, or other reagents that might be environmentally suspect such as metal complexes and the like.
  • catalytic chemical azidolysis of epoxides is typically performed using environmentally unfriendly metals, such as chromium, cobalt or titanium complexes, in organic solvents, such as dichloromethane, acetonitrile or dimethylformamide.
  • enzymes are often more selective and more efficient catalysts than their chemical counterparts designed by man.
  • halohydrins and epoxides are used as building blocks for various pharmaceutical products.
  • Halohydrins are often considered as direct precursors for epoxides. Ring closure of an optically pure halohydrin generally leads to an optically pure epoxide.
  • a kinetic resolution of a halohydrin containing an aromatic group, such as 2-chloro-1-phenylethanol, with a halohydrin dehalogenase from Agrobacterium radiobacter AD1 has been described (Lutje Spelberg et al., Tetrahedron: Asymmetry, 1999, 10, 2863).
  • the present invention provides a process wherein, optionally substituted, epoxides may be converted to alcohols in a highly enantioselective manner. It has been found that the desired enantioselectivity may be accomplished by enzymatically converting an, optionally substituted, epoxide of the formula
  • R 1 is hydrogen or an, optionally substituted, aromatic or aliphatic group, to a mixture of an optically enriched epoxide of the formula (I) and an optically enriched alcohol of the formula
  • R 2 is chosen from the group of I, Cl, Br, CN, N 3 , NO 2 , NO 3 , SCN, OCN, OR′, NHR′, SR′, SnR′, SeR′, PR′ and CO 2 R′, wherein R′ is chosen from hydrogen, amino groups, hydroxyl groups, alkyl groups, aryl groups, aralkyl, alkenyl and cycloalkyl groups, which process comprises reacting the epoxide with an anionic nucleophile (R 2 ⁇ ) in the presence of a halohydrin dehalogenase.
  • R 2 ⁇ anionic nucleophile
  • the present process is highly regiospecific.
  • two different products may be formed: one in which the —OH group is present at the carbon atom adjacent to the R 1 group, and one in which the —OH group is present at the carbon atom on the distal end from the R 1 group.
  • the isomer with the —OH group at the carbon atom adjacent to the R 1 is formed.
  • the product of the reaction is a building block for a wide variety of pharmaceutical compounds.
  • 2-azido-1-phenylethanol which may be formed by the enzymatic reaction of sodium azide and styrene oxide, can be converted to biologically active 2-aminophenyl ethanol by catalytic hydrogenation.
  • R 1 group is hydrogen or an, optionally substituted, aromatic or aliphatic group, which preferably contains from 1 to 20 carbon atoms.
  • R 1 is chosen from the group of optionally substituted alkyl, aryl, aralkyl, alkenyl, cycloalkyl, and alkoxy groups.
  • Preferred examples of the alkyl group represented by R 1 include straight or branched alkyl groups having 1 to 15 carbon atoms such as a methyl group, ethyl group, propyl group, isopropyl group, butyl group, pentyl group, hexyl group, heptyl group or dodecyl group.
  • Representative epoxides from this group include 1,2-epoxy propane, 1,2-epoxy-3-metylpentane and 1,2-epoxy hexane.
  • the alkyl group can have substituents such as a halogen atom, leading to for example epichlorohydrin, epifluorohydrin or epibromohydrin.
  • the alkyl group can have a substituent such as an hydroxyl group, for example glycidol.
  • the alkyl group can have a unsubstituted or substituted amino group such as amino, methylamino or dimethylamino.
  • aryl groups represented by R 1 include phenyl and naphtyl groups. Styrene oxide or styrene oxides having a substituent or multiple substituents on the aromatic ring are examples of the phenyl group.
  • epoxides are styrene oxide, 4-nitrostyrene oxide, 2-nitrostyrene oxide, 3-nitrostyrene oxide, 3-chlorostyrene oxide, 4 chlorostyrene oxide or 2,3-dichlorostyrene oxide.
  • aralkyl groups represented by R 1 include a benzyl group, 2-phenylethyl group and a 1-naphtylmethyl group.
  • alkenyl groups represented by R 1 include a vinyl group, allyl group and 5-hexenyl group.
  • Examples of cycloalkyl groups represented by R 1 include a cyclopropyl group, cyclobutyl group, cyclopentyl group and cyclohexyl group.
  • Examples of alkoxy groups represented by R 1 include a phenoxy group, 4-nitrophenoxy group, napthyloxy group, methoxy group, hexyloxy group and vinyloxy group.
  • a preferred class of epoxides that may be converted has the following formula:
  • This class of epoxides may be substituted at the carbon atom bearing the R 1 group by a —CH 2 R 4 group, wherein the R 4 group may be independently chosen from Cl, Br and I.
  • Preferred examples of this class of epoxides are epichlorohydrin, epibromohydrin and 2-(chloromethyl)-2-methyloxirane. It has been found that during conversion to an alcohol, particularly when azide is used as the nucleophile, the enantionmer of the epoxide which is not converted is racemized. Due to this racemization a total conversion of epichlorohydrin is achieved and the product is obtained in high optically purity.
  • the epoxide is a stryrene oxide, which may or may not be substituted.
  • the product obtained will be a mixture of two compounds having their alcohol functionality on their carbon atom ⁇ or ⁇ to the aromatic ring.
  • the non-catalyzed chemical ring opening of styrene oxide by sodium azide will yield a mixture of regio-isomers with the alcohol functionality on the ⁇ and on the ⁇ -position in a molar ratio of 2:98 ( ⁇ : ⁇ ).
  • the other regio-isomer i.e. wherein the alcohol functionality is present at the carbon atom a to the aromatic ring.
  • the carbon atom ⁇ to the aromatic ring is the carbon atom within the epoxide ring which bears the aromatic ring substitutent.
  • R 1 is an ortho-, meta-, or para-substituent chosen from the group of —NO 2 , —NH 2 , —CH 3 , —OCH 3 , —OCH 2 CH 3 , —OH, —F, —Cl, —Br, —I, —COOH and —CN. It has been found that the regiospecificity is particularly high for the conversion of these epoxides.
  • the epoxide can be present in solubilized form in a concentration of 1 to 300 mM or as a second solid or liquid phase in concentration up to 300 mM in the reaction medium.
  • the epoxide itself can be the second phase or it can be dissolved in a second organic phase. This can be done by dissolving the epoxide in an organic solvent which is immiscible with water, such as hexane or octane. The obtained solution is then brought into contact with the aqueous phase containing the enzyme and the two phases are vigorously mixed.
  • the use of such a second phase has the advantage that the separation of the epoxide and the alcohol after the reaction can be simplified.
  • the alcohol is expected to remain solubilized in the aqueous phase and the epoxide can typically be recovered from the organic phase.
  • the epoxide is prior to its conversion brought in an aqueous medium in which it will preferably be present in an amount of 0.01 to 20 wt. %, based on the combined weights of the aqueous medium and the epoxide.
  • nucleophile chosen to convert the epoxide in a process according to the invention will normally depend on the nature of the objective product.
  • Suitable nucleophiles include of I, Cl, Br, CN, N 3 , NO 2 , NO 3 , SCN, OCN, OR′, NHR′, SR′, SnR′, SeR′, PR′ and CO 2 R′, wherein R′ is chosen from hydrogen, amino groups, hydroxyl groups, alkyl groups, aryl groups, aralkyl, alkenyl and cycloalkyl groups.
  • substituted alkyl groups, aryl groups, aralkyl, alkenyl and cycloalkyl groups are also encompassed.
  • R′ When R′ is an alkyl group, it preferably contains from 1 to 15, more preferably from 1 to 6 carbon atoms. When R′ is an aryl group, it preferably is a phenyl or a naphtyl group. Preferred aralkyl groups which may be represented by R′ include benzyl, 2-phenylethyl and 1-naphtylmethyl groups. Preferred alkenyl groups from which R′ may be chosen are vinyl and allyl groups. When R′ is a cycloalkyl group, it may suitably have from 3 to 12 carbon atoms. Preferred cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • the nucleophile is NO 2 ⁇ or N 3 ⁇ .
  • the nucleophile may be employed in the form of a salt, for instance as a sodium or potassium salt.
  • An excess of the nucleophilic reagent may lead to the non-enantioselective formation of the unwanted regio-isomer of the objective product. This may be circumvented by either performing the reaction on a shorter time-scale, performing the reaction at a lower temperature, employing a larger quantity of the enzyme, or by adding the nucleophilic reagent to the reaction mixture in a slower fashion.
  • the nucelophile will be used in an amount of 0.6 to 100 molar equivalents with respect to the epoxide, depending on the position of the equilibrium between the epoxide and the alcohol.
  • the nucelophile will be used in an amount of 0.6 to 100 molar equivalents with respect to the epoxide, depending on the position of the equilibrium between the epoxide and the alcohol.
  • 0.6 molar equivalents suffice to achieve a substantially completed kinetic resolution since the position of the equilibrium favors the formation of the alcohol over the epoxide.
  • sodium chloride as the nucleophile, an excess (50-100 molar equivalents) are preferably added to favor the formation of the alcohol.
  • a buffered aqueous medium to which the epoxide is solubilized or is added as a second solid or liquid phase.
  • Suitable buffers are for example Tris-buffer (2 amino-2-(hydroxymethyl)-1,3 propanediol adjusted to a desired pH with H 2 SO 4 ), glycine-buffer (glycine adjusted to a desired pH by NaOH), phosphates buffer or MOPS buffer (4-morpholinepropanesulfonic acid adjusted to a desired pH with NaOH). These are preferably used a concentration of 50 to 250 mM.
  • co-solvents like dimethyl sulfoxide, tetrahydrofuran or acetonitrile may be added to increase the solubility of the epoxide.
  • Co-solvents may be added in amounts of 5 vol. % up to 50 vol. %.
  • An increasing percentage of co-solvent may favor the solubility of the epoxide.
  • a disadvantageous inactivation of the enzyme can be observed at higher co-solvent concentrations.
  • the pH of the medium preferably lies between 3 and 12, more preferably between 6.5 and 8.
  • the temperature at which the reaction is carried out preferably lies between 0 to 60° C., more preferably between 20 and 30° C.
  • the enzyme used is a halohydrin dehalogenase.
  • a highly suitable halohydrin dehalogenase is a polypeptide having an amino acid sequence as shown in SEQ ID NO 2 or a homologue or functional derivative thereof.
  • a homologue refers to a sequence which is at least for 90% homologous, and preferably at least 90% identical, to the sequence of which it is a homologue.
  • a functional derivative is a polypeptide which has undergone a minor derivatization or modification substantially without adversely affecting the enzymatic and catalytic properties of the polypeptide.
  • Suitable examples of enzymes that can be used are halohydrin dehalogenase of Agrobacterium radiobacter (CBS 750.97), Mycobacterium sp. strain GP1 (Poelarends et al J. Bacteriol., 1999, 181, 2050) or Arthrobacter sp. strain AD2 (van den Wijngaard et al., J. Bacteriol., 1991, 124).
  • Particular good results have been obtained using a halohydrin dehalogenase derived from Agrobacterium radiobacter strain AD1 deposited at the Centraal Bureau voor de Schimmelcultures on May 7, 1997 under deposit number CBS 750.97.
  • Another enzyme obtained from this organism has been described extensively in the international patent application 98/53081 for its epoxide hydrolase activity.
  • an enzyme used according to the invention should be distinguished from epoxide hydrolases.
  • the latter have been described extensively in Archer, Tetrahedron, 53 (1997), pp. 15617-15662. The only feature that both types of enzymes may have in common is that they can be isolated from Agrobacterium radiobacter strain AD1.
  • Lutje Spelberg et al., Tetrahedron: Asymmetry, 9 (1998), pp. 459-466 and European patent application 0 879 890 relate to applications of an epoxide hydrolase.
  • the enzyme can be added as whole cells, in lyophilized form as a crude extract or as a purified enzyme.
  • the enzyme can be immobilized on a macroscopic carriers such as cellulose, sephadex or dextran.
  • the enzyme can also be applied as crosslinked enzyme crystals (CLEC's) or entrapped in reversed micelles.
  • CLEC's crosslinked enzyme crystals
  • an enzyme solution is mixed with a buffer solution containing a nucleophile and an epoxide.
  • additives such as mercapto ethanol or glycerol can be added to the reaction mixture to stabilize the enzyme.
  • the whole reaction mixture can be extracted using organic solvents such as diethylether, ethyl acetate, dichloromethane or toluene.
  • organic solvents such as diethylether, ethyl acetate, dichloromethane or toluene.
  • the epoxide and the alcohol can subsequently be separated by techniques such as crystallisation (in the case of solid substances), fraction distillation or flash chromatography on silica 60H using for example heptane/ethylacetate(ratio 7:3) as eluent.
  • the enantiomeric composition of the epoxides and alcohols can be determined using chiral gaschromatography or chiral HPLC.
  • a gene library of A. radiobacter AD1 was constructed in the cosmid vector pLAFR3. After in vitro packaging, the library was transduced to E. coli HB101. Transconjugants were screened for dehalogenase activity with 1,3-dichloro-2-propanol.
  • the halohydrin dehalogenase gene, designated hheC was sequenced and subsequently amplified by PCR and cloned behind the T7 promotor of the expression vector pGEF + , yielding pGEFhheC.
  • the halohydrin dehalogenase gene was overexpressed up to 30% of soluble protein by introduction of pGEFhheC in E. coli BL21(DE3).
  • HheC has the sequence shown as SEQ ID NO 1.
  • Plasmid DNA was transformed by electroporation to competent E. coli BL21 (DE3) cells, which were then plated out on LB medium containing tetracycline and incubated overnight at 30° C.
  • a preculture was started by inoculating 100 ml of LB medium containing tetracycline with the transformants from a plate to a initial OD 600 of 0.1.
  • the culture was incubated at 30° C. until an OD 600 of 1-2 was reached, diluted in 1 l of LB medium containing tetracycline and incubated overnight at 20° C.
  • the cells were subsequently centrifuged, washed and resuspended.
  • a crude extract was prepared by ultrasonic disruption and centrifugation of the cells. This was followed by a purification step with a Resource Q column yielding the enzyme having SEQ ID NO 2.
  • SEQ ID NO 1 DNA Sequence of the Halohydrin Dehalogenase Gene from AD1 (Capitals Only) taaaatctcggcaaatatctagcgatcataggatataaaggatctgagtA TGTCAACCGCAATTGTAACAAACGTTAAGCATTTTGGGGGAATGGGGTCT GCACTTCGTCTCGGAAGCAGGACATACAGTGGCTTGCCACGATGAAAG CTTCAAACAAAAGGACGAACTTGAAGCCTTTGCCGAAACCTATCCACAAC TCAAACCAATGTCGGAACAAGAACCAGCGGAACTCATCGAGGCAGTTACC TCCGCTTATGGTCAAGTTGATGTACTTGTGAGCAACGACATATTCGCACC AGAGTTCCAACCCATAGATAAATACGCTGTAGAGGACTATCGCGGTGCGG TCGAGGCGCTACAAATTAGACCATTTGCACTGGTCAACGCCGTTGCAAGT CAAATGAAGAAGCGCAAAAGCGGACATATTATATCGCGGTGC
  • SEQ ID NO 2 Amino Acid Sequence of HheC MSTAIVTNVKHFGGMGSALRLSEAGHTVACHDESFKQKDELEAFAETYPQ LKPMSEQEPAELIEAVTSAYGQVDVLVSNDIFAPEFQPIDKYAVEDYRGA VEALQIRPFALVNAVASQMKKRKSGHIIFITSATPFGPWKELSTYTSARA GACTLANALSKELGEYNIPVFAIGPNYLHSEDSPYFYPTEPWKTNPEHVA HVKKVTALQRLGTQKELGELVAFLASGSCDYLTGQVFWLAGGFPMIERWP GMPE

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
US10/302,788 2000-05-25 2002-11-22 Enzymatic conversion of epoxides Abandoned US20030124693A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/833,933 US7695942B2 (en) 2000-05-25 2007-08-03 Enzymatic conversion of epoxides

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP00201874A EP1158054A1 (fr) 2000-05-25 2000-05-25 Conversion enzymatique d'époxydes
EP00201874.5 2000-05-25
PCT/NL2001/000403 WO2001090397A1 (fr) 2000-05-25 2001-05-23 Conversion enzymatique d'epoxydes

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/NL2001/000403 Continuation WO2001090397A1 (fr) 2000-05-25 2001-05-23 Conversion enzymatique d'epoxydes

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/833,933 Continuation US7695942B2 (en) 2000-05-25 2007-08-03 Enzymatic conversion of epoxides

Publications (1)

Publication Number Publication Date
US20030124693A1 true US20030124693A1 (en) 2003-07-03

Family

ID=8171560

Family Applications (2)

Application Number Title Priority Date Filing Date
US10/302,788 Abandoned US20030124693A1 (en) 2000-05-25 2002-11-22 Enzymatic conversion of epoxides
US11/833,933 Expired - Fee Related US7695942B2 (en) 2000-05-25 2007-08-03 Enzymatic conversion of epoxides

Family Applications After (1)

Application Number Title Priority Date Filing Date
US11/833,933 Expired - Fee Related US7695942B2 (en) 2000-05-25 2007-08-03 Enzymatic conversion of epoxides

Country Status (8)

Country Link
US (2) US20030124693A1 (fr)
EP (2) EP1158054A1 (fr)
JP (1) JP2004504015A (fr)
AT (1) ATE337408T1 (fr)
AU (1) AU2001260802A1 (fr)
DE (1) DE60122505T3 (fr)
ES (1) ES2271010T3 (fr)
WO (1) WO2001090397A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007071599A3 (fr) * 2005-12-21 2007-08-16 Basf Ag Procede de fabrication d’un alcool tertiaire enrichi optiquement
US20090042261A1 (en) * 2006-03-03 2009-02-12 Basf Se Process for the preparation of optically active 5-substituted 2-oxazolidinones from racemic epoxides and cyanate employing a halohydrin dehalogenase

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100651393B1 (ko) 2001-02-28 2006-11-28 에스케이 주식회사 가수분해 효소를 이용한 (ｒ)-1-아미노-2-프로판올의제조방법
WO2004015132A2 (fr) * 2002-08-09 2004-02-19 Codexis, Inc. Production par voie enzymatique de derives de 3-acide hydroxybutyrique substitue en position 4
US7132267B2 (en) 2002-08-09 2006-11-07 Codexis, Inc. Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives and vicinal cyano, hydroxy substituted carboxylic acid esters
US7588928B2 (en) 2003-08-11 2009-09-15 Codexis, Inc. Halohydrin dehalogenases and related polynucleotides
US7541171B2 (en) 2003-08-11 2009-06-02 Codexis, Inc. Halohydrin dehalogenases and related polynucleotides
CA2535255A1 (fr) 2003-08-11 2005-02-24 Codexis, Inc. Deshalogenases d'halohydrine ameliorees et polynucleotides correspondants
JP2008537477A (ja) * 2005-02-23 2008-09-18 コデクシス， インコーポレイテッド 改良されたハロヒドリンデハロゲナーゼおよび関連のポリヌクレオチド
WO2007128469A1 (fr) * 2006-05-03 2007-11-15 Dsm Ip Assets B.V. Procédé de préparation de nitriles énantiomériquement enrichis
WO2007137816A1 (fr) * 2006-05-30 2007-12-06 Dsm Ip Assets B.V. Procédé de préparation d'intermédiaires époxidés pour des composés pharmaceutiques tels que des statines
WO2010080635A2 (fr) 2008-12-18 2010-07-15 Codexis, Inc. Polypeptides de halohydrine déshalogénase recombinants
US9150884B2 (en) 2011-03-08 2015-10-06 Arizona Board Of Regents, A Body Corporate Of The State Of Arizona, Acting For And On Behalf Of Arizona State University Microbial conversion of glucose to styrene and its derivatives
CN104749273B (zh) * 2015-03-12 2017-04-12 浙江工业大学 一种检测水中叠氮根离子或氰离子的方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5210031A (en) † 1989-07-20 1993-05-11 Nitto Chemical Industry Co., Ltd. Process for the production of R(-)-4-halo-3-hydroxybutyronitrile
JP3073037B2 (ja) * 1991-03-04 2000-08-07 三菱レイヨン株式会社 ハロヒドリンエポキシダ−ゼ遺伝子を有する組換え体プラスミドおよび該プラスミドにより形質転換された微生物
JP3728045B2 (ja) † 1997-01-31 2005-12-21 三菱レイヨン株式会社 ハロヒドリンより光学活性ジオールへの変換を触媒する新規なタンパク質
EP0879890A1 (fr) * 1997-05-21 1998-11-25 Rijksuniversiteit te Groningen Hydrolases d'époxide enantiosélective et gènes codant pour celles-ci

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007071599A3 (fr) * 2005-12-21 2007-08-16 Basf Ag Procede de fabrication d’un alcool tertiaire enrichi optiquement
US20080299626A1 (en) * 2005-12-21 2008-12-04 Basf Aktiengesellschaft Process For the Production of an Optically Enriched Tertiary Alcohol
US8198069B2 (en) 2005-12-21 2012-06-12 Basf Se Method of producing an optically enriched tertiary alcohol from an epoxide using halohydrin dehalogenase
US20090042261A1 (en) * 2006-03-03 2009-02-12 Basf Se Process for the preparation of optically active 5-substituted 2-oxazolidinones from racemic epoxides and cyanate employing a halohydrin dehalogenase
US7993904B2 (en) 2006-03-03 2011-08-09 Basf Se Process for the preparation of optically active 5-substituted 2-oxazolidinones from racemic epoxides and cyanate employing a halohydrin dehalogenase

Also Published As

Publication number Publication date
DE60122505T2 (de) 2007-05-03
EP1158054A1 (fr) 2001-11-28
ATE337408T1 (de) 2006-09-15
DE60122505T3 (de) 2011-07-28
DE60122505D1 (de) 2006-10-05
ES2271010T3 (es) 2007-04-16
EP1287155B2 (fr) 2011-01-12
EP1287155A1 (fr) 2003-03-05
US7695942B2 (en) 2010-04-13
US20080220485A1 (en) 2008-09-11
JP2004504015A (ja) 2004-02-12
EP1287155B1 (fr) 2006-08-23
WO2001090397A1 (fr) 2001-11-29
AU2001260802A1 (en) 2001-12-03

Similar Documents

Publication Publication Date Title
US7695942B2 (en) Enzymatic conversion of epoxides
Poessl et al. Non‐racemic halohydrins via biocatalytic hydrogen‐transfer reduction of halo‐ketones and one‐pot cascade reaction to enantiopure epoxides
EP1994162B1 (fr) Procédé de préparation de 2-oxazolidinones 5-substituées optiquement actives à partir d'époxydes racémiques et de cyanate en employant une halohydrine déshalogénase
Haak et al. Synthesis of enantiopure chloroalcohols by enzymatic kinetic resolution
WO2007128469A1 (fr) Procédé de préparation de nitriles énantiomériquement enrichis
Xu et al. Biocatalytic resolution of glycidyl aryl ethers by Trichosporon loubierii: cell/substrate ratio influences the optical purity of (R)-epoxides
EP1966385B1 (fr) Procede de fabrication d un alcool tertiaire enrichi optiquement
JP4843813B2 (ja) 酵素を用いるＲ−体又はＳ−体のα−置換ヘテロサイクリックカルボン酸及びこれと反対鏡像の鏡像異性体のα−置換ヘテロサイクリックカルボン酸エステルの調製方法
JP4843812B2 (ja) 酵素を使用するラセミα−置換ヘテロ環式カルボン酸の光学分割方法
US7067291B2 (en) Biocatalytic preparation of enantiomerically enriched aminopentanenitrile
KR100567899B1 (ko) 효소적 방법에 의한 트랜스-(1ｓ,2ｓ)-2-브로모-1-인다닐 아세테이트의 제조방법
JP3741758B2 (ja) 光学活性グリセロール誘導体の製法

Legal Events

Date Code Title Description
AS Assignment

Owner name: RIJKSUNIVERSITEIT GRONINGEN, NETHERLANDS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SPELBERG, JEFFREY HARALD LUTJE;JANSSEN, DICK BAREND;REEL/FRAME:013780/0805

Effective date: 20030127

AS Assignment

Owner name: ENZIS PATENT B.V., NETHERLANDS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:GRONINGEN, RIJKSUNIVERSITEIT;REEL/FRAME:014116/0444

Effective date: 20030311

AS Assignment

Owner name: CODEXIS INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ENZIS PATENT B.V.;REEL/FRAME:017744/0699

Effective date: 20060501

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION