SK143793A3 - The enzymatic process for the stereoselective preparation of a heterobicyclic alcohol enantiomer - Google Patents

The enzymatic process for the stereoselective preparation of a heterobicyclic alcohol enantiomer Download PDF

Info

Publication number: SK143793A3
Authority: SK; Slovakia
Prior art keywords: formula; enantiomer; alcohol; atom; compound
Prior art date: 1992-12-21

Application number

SK1437-93A

Other languages

English (en)

Slovak (sk)

Inventor

Nicolaas Buizer

Chris G Kruse

Der Laan Melle Van

Georges Langrand

Scharrenburg Gustaaf J M Van

Maria C Snoek

Original Assignee

Duphar Int Res

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.)

1992-12-21

Filing date

1993-12-16

Publication date

1994-09-07

1993-12-16 Application filed by Duphar Int Res filed Critical Duphar Int Res

1994-09-07 Publication of SK143793A3 publication Critical patent/SK143793A3/sk

Links

-1 heterobicyclic alcohol enantiomer Chemical class 0.000 title claims abstract description 33
238000000034 method Methods 0.000 title claims abstract description 33
238000002360 preparation method Methods 0.000 title claims abstract description 16
230000002255 enzymatic effect Effects 0.000 title claims abstract description 12
230000000707 stereoselective effect Effects 0.000 title claims abstract description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 93
238000006243 chemical reaction Methods 0.000 claims abstract description 56
150000002148 esters Chemical class 0.000 claims abstract description 30
150000001298 alcohols Chemical class 0.000 claims abstract description 20
150000004885 piperazines Chemical class 0.000 claims abstract description 13
125000001424 substituent group Chemical group 0.000 claims abstract description 12
230000032050 esterification Effects 0.000 claims abstract description 9
238000005886 esterification reaction Methods 0.000 claims abstract description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
229910052736 halogen Inorganic materials 0.000 claims abstract description 6
150000002367 halogens Chemical class 0.000 claims abstract description 6
230000007062 hydrolysis Effects 0.000 claims abstract description 6
238000006460 hydrolysis reaction Methods 0.000 claims abstract description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
239000001257 hydrogen Substances 0.000 claims abstract description 5
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 40
108090001060 Lipase Proteins 0.000 claims description 16
239000004367 Lipase Substances 0.000 claims description 16
102000004882 Lipase Human genes 0.000 claims description 16
235000019421 lipase Nutrition 0.000 claims description 16
102000004190 Enzymes Human genes 0.000 claims description 15
108090000790 Enzymes Proteins 0.000 claims description 15
230000006340 racemization Effects 0.000 claims description 15
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
125000004432 carbon atom Chemical group C* 0.000 claims description 10
239000003795 chemical substances by application Substances 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 8
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
230000000694 effects Effects 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
229940014800 succinic anhydride Drugs 0.000 claims description 6
150000001244 carboxylic acid anhydrides Chemical class 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
108090000371 Esterases Proteins 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
239000011737 fluorine Chemical group 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
125000003373 pyrazinyl group Chemical group 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 5
238000000926 separation method Methods 0.000 abstract description 5
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
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VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
238000003776 cleavage reaction Methods 0.000 description 15
239000000203 mixture Substances 0.000 description 14
230000007017 scission Effects 0.000 description 14
239000002904 solvent Substances 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
239000010410 layer Substances 0.000 description 12
239000012044 organic layer Substances 0.000 description 11
238000003756 stirring Methods 0.000 description 11
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
238000001914 filtration Methods 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
238000010992 reflux Methods 0.000 description 9
239000007787 solid Substances 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
230000003287 optical effect Effects 0.000 description 8
241000179532 [Candida] cylindracea Species 0.000 description 7
125000000217 alkyl group Chemical group 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000000047 product Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
239000013543 active substance Substances 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
238000001035 drying Methods 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
238000007127 saponification reaction Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
WJMOWGFGRONZPA-UHFFFAOYSA-N aziridin-1-yl-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CC1 WJMOWGFGRONZPA-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000003480 eluent Substances 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000000758 substrate Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
239000008096 xylene Substances 0.000 description 3
RCTJWTFYUAYKDB-UHFFFAOYSA-N (6-chloro-8-nitro-3,4-dihydro-2h-1,4-benzoxazin-3-yl)methanol Chemical compound C1=C(Cl)C=C([N+]([O-])=O)C2=C1NC(CO)CO2 RCTJWTFYUAYKDB-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
241000589540 Pseudomonas fluorescens Species 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000012670 alkaline solution Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical group C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical compound ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
239000002178 crystalline material Substances 0.000 description 2
NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical group OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000012535 impurity Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
150000003333 secondary alcohols Chemical class 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 2
238000005406 washing Methods 0.000 description 2
WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 1
GWQOQQVKVOOHTI-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-3-ylmethanol Chemical class C1=CC=C2OC(CO)COC2=C1 GWQOQQVKVOOHTI-UHFFFAOYSA-N 0.000 description 1
YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical compound [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical compound NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 description 1
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101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
241000222120 Candida <Saccharomycetales> Species 0.000 description 1
241000146387 Chromobacterium viscosum Species 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
241000768847 Enantiosis Species 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
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235000017388 Geotrichum candidum Nutrition 0.000 description 1
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241001465754 Metazoa Species 0.000 description 1
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SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
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240000000064 Penicillium roqueforti Species 0.000 description 1
235000002233 Penicillium roqueforti Nutrition 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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101001064559 Pseudomonas fluorescens Lipase Proteins 0.000 description 1
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KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
241000223258 Thermomyces lanuginosus Species 0.000 description 1
XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
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BGONDVUDLPQJNA-UHFFFAOYSA-N [1-(trifluoromethyl)anthracen-9-yl]methanol Chemical compound C1=CC(C(F)(F)F)=C2C(CO)=C(C=CC=C3)C3=CC2=C1 BGONDVUDLPQJNA-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
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JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical group C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
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WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
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230000003197 catalytic effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000002894 chemical waste Substances 0.000 description 1
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238000004587 chromatography analysis Methods 0.000 description 1
230000001010 compromised effect Effects 0.000 description 1
150000003972 cyclic carboxylic anhydrides Chemical class 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
238000005661 deetherification reaction Methods 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
239000003814 drug Substances 0.000 description 1
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238000006911 enzymatic reaction Methods 0.000 description 1
238000010931 ester hydrolysis Methods 0.000 description 1
WNMORWGTPVWAIB-UHFFFAOYSA-N ethenyl 2-methylpropanoate Chemical compound CC(C)C(=O)OC=C WNMORWGTPVWAIB-UHFFFAOYSA-N 0.000 description 1
MEGHWIAOTJPCHQ-UHFFFAOYSA-N ethenyl butanoate Chemical compound CCCC(=O)OC=C MEGHWIAOTJPCHQ-UHFFFAOYSA-N 0.000 description 1
UIWXSTHGICQLQT-UHFFFAOYSA-N ethenyl propanoate Chemical compound CCC(=O)OC=C UIWXSTHGICQLQT-UHFFFAOYSA-N 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
125000001183 hydrocarbyl group Chemical group 0.000 description 1
LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000003921 oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000000039 preparative column chromatography Methods 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000003723 serotonin 1A agonist Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007858 starting material Substances 0.000 description 1
RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
229920001567 vinyl ester resin Polymers 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
- C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
- C07D327/06—Six-membered rings
- 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
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
- 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
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/14—Nitrogen or oxygen as hetero atom and at least one other diverse hetero ring atom in the same ring
- 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
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/004—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of alcohol- or thiol groups in the enantiomers or the inverse reaction
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Wood Science & Technology (AREA)
Zoology (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Microbiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Genetics & Genomics (AREA)
Health & Medical Sciences (AREA)
Biochemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
General Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Analytical Chemistry (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

SK1437-93A 1992-12-21 1993-12-16 The enzymatic process for the stereoselective preparation of a heterobicyclic alcohol enantiomer SK143793A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP92204043		1992-12-21

Publications (1)

Publication Number	Publication Date
SK143793A3 true SK143793A3 (en)	1994-09-07

Family

ID=8211159

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1437-93A SK143793A3 (en)	1992-12-21	1993-12-16	The enzymatic process for the stereoselective preparation of a heterobicyclic alcohol enantiomer

Country Status (24)

Country	Link
US (1)	US5914263A (cs)
EP (2)	EP0939135A1 (cs)
JP (1)	JPH06237790A (cs)
KR (1)	KR940014808A (cs)
CN (1)	CN1255496A (cs)
AT (1)	ATE182367T1 (cs)
AU (1)	AU674547B2 (cs)
BG (1)	BG61511B1 (cs)
CA (1)	CA2111607A1 (cs)
CZ (2)	CZ286077B6 (cs)
DE (1)	DE69325698T2 (cs)
DK (1)	DK0605033T3 (cs)
ES (1)	ES2134241T3 (cs)
FI (1)	FI935676A7 (cs)
GR (1)	GR3031446T3 (cs)
IL (1)	IL108090A (cs)
NO (1)	NO934652L (cs)
NZ (1)	NZ250478A (cs)
PL (2)	PL177831B1 (cs)
RO (1)	RO112517B1 (cs)
RU (1)	RU2124506C1 (cs)
SK (1)	SK143793A3 (cs)
TW (1)	TW381120B (cs)
ZA (1)	ZA939435B (cs)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2724184B1 (fr) *	1994-09-05	1997-01-03	Rhone Poulenc Chimie	Procede de resolution d'un melange d'alcools stereoisomeres
AU701883B2 (en) *	1996-01-25	1999-02-11	Duphar International Research B.V.	Process for the stereoselective preparation of a hetero-bicyclic alcohol enantiomer
DE19706337A1 (de) *	1997-02-19	1998-08-20	Basf Ag	Verfahren zur Herstellung von enantiomerenreinen Estern
ES2323451T7 (es)	2001-07-20	2011-08-01	Psychogenics Inc.	Tratamiento para el trastorno de hiperactividad con deficit de atencion.
FR2853327B1 (fr) *	2003-04-04	2012-07-27	Solvay	Procede pour la fabrication de derives de beta-aminoacides enantiopurs et derives de beta-aminoacides enantiopurs
KR100527231B1 (ko) *	2003-06-03	2005-11-08	엔자이텍 주식회사	무수숙신산에 의한 광학활성 1,2-디올 유도체와 이의 에스테르 제조방법
ES2405404T3 (es)	2003-10-29	2013-05-31	Wyeth Llc	Composiciones farmacéuticas de liberación sostenida que comprenden aplindore y sus derivados
DE102004004719A1 (de) *	2004-01-29	2005-08-18	Basf Ag	Verfahren zur Herstellung von enantiomerenreinen Aminoalkoholen
TW200811182A (en) *	2006-05-25	2008-03-01	Wyeth Corp	Oxindoledioxans, synthesis thereof, and intermediates thereto
CZ302204B6 (cs) *	2009-10-21	2010-12-15	Mikrobiologický ústav AV CR, v.v.i.	Zpusob výroby opticky cistých stereomeru silybinu A a silybinu B
CA2932003A1 (en) *	2013-12-11	2015-06-18	F. Hoffmann-La Roche Ag	Process for the preparation of chiral 2-aryl morpholines

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3692775A (en) *	1969-03-17	1972-09-19	Allied Chem	Racemization of d-or l-{60 -amino-caprolactam in the presence of metal ions
GB1389217A (en) *	1971-06-02	1975-04-03	Glaxo Lab Ltd	Phenylglycine derivatives
FR2479825A1 (fr) *	1980-04-04	1981-10-09	Fabre Sa Pierre	Benzodioxanne 1,4 methoxy-2 propanolamines, leur preparation et leur application en tant que medicaments
FR2523961B1 (fr) *	1982-03-23	1985-08-30	Centre Nat Rech Scient	Procede de preparation d'un alpha-amino-acide libre l
US4659671A (en) *	1983-07-01	1987-04-21	Massachusetts Institute Of Technology	Enzymatic separation of racemic mixtures of hydroxy compounds
AU577802B2 (en) *	1983-10-17	1988-10-06	Duphar International Research B.V.	Blood-pressure lowering piperazine derivatives
EP0189612B1 (en) *	1984-12-21	1992-11-04	Duphar International Research B.V	New pharmaceutical compositions having a psychotropic activity
EP0190472B1 (en) *	1984-12-21	1989-07-12	Duphar International Research B.V	New pharmaceutical compositions having anti-psychotic properties
IT1201408B (it) *	1985-03-22	1989-02-02	Montedison Spa	Processo per la preparazione biotecnologica di acidi alfa-arilalcanoici otticamente attivi
IE74200B1 (en) *	1987-09-11	1997-07-16	Duphar Int Res	Anxiolytically active piperazine derivatives
IL92544A0 (en) *	1988-12-08	1990-08-31	Duphar Int Res	Piperazine derivatives,their preparation and pharmaceutical compositions containing them
US5166062A (en) *	1990-01-26	1992-11-24	University Of New Mexico	Methods for separating diol and triol stereoisomers from a stereoisomer mixture

1993
- 1993-12-09 EP EP98204281A patent/EP0939135A1/en not_active Withdrawn
- 1993-12-09 AT AT93203451T patent/ATE182367T1/de not_active IP Right Cessation
- 1993-12-09 DK DK93203451T patent/DK0605033T3/da active
- 1993-12-09 ES ES93203451T patent/ES2134241T3/es not_active Expired - Lifetime
- 1993-12-09 DE DE69325698T patent/DE69325698T2/de not_active Expired - Fee Related
- 1993-12-09 EP EP93203451A patent/EP0605033B1/en not_active Expired - Lifetime
- 1993-12-15 ZA ZA939435A patent/ZA939435B/xx unknown
- 1993-12-16 CZ CZ19932784A patent/CZ286077B6/cs not_active IP Right Cessation
- 1993-12-16 NZ NZ250478A patent/NZ250478A/en unknown
- 1993-12-16 RO RO93-01714A patent/RO112517B1/ro unknown
- 1993-12-16 CA CA002111607A patent/CA2111607A1/en not_active Abandoned
- 1993-12-16 NO NO934652A patent/NO934652L/no not_active Application Discontinuation
- 1993-12-16 FI FI935676A patent/FI935676A7/fi unknown
- 1993-12-16 SK SK1437-93A patent/SK143793A3/sk unknown
- 1993-12-16 BG BG98305A patent/BG61511B1/bg unknown
- 1993-12-17 PL PL93301539A patent/PL177831B1/pl not_active IP Right Cessation
- 1993-12-17 AU AU52502/93A patent/AU674547B2/en not_active Ceased
- 1993-12-17 JP JP5343229A patent/JPH06237790A/ja active Pending
- 1993-12-17 KR KR1019930028170A patent/KR940014808A/ko not_active Abandoned
- 1993-12-17 PL PL93332294A patent/PL178517B1/pl not_active IP Right Cessation
- 1993-12-18 TW TW082110748A patent/TW381120B/zh active
- 1993-12-20 IL IL10809093A patent/IL108090A/en not_active IP Right Cessation
- 1993-12-20 RU RU93055675A patent/RU2124506C1/ru not_active IP Right Cessation
1997
- 1997-07-23 US US08/899,155 patent/US5914263A/en not_active Expired - Fee Related
- 1997-09-15 CZ CZ19972905A patent/CZ286162B6/cs not_active IP Right Cessation
1999
- 1999-10-06 CN CN99121080A patent/CN1255496A/zh active Pending
- 1999-10-07 GR GR990402535T patent/GR3031446T3/el unknown

Also Published As

Publication number	Publication date
ZA939435B (en)	1994-08-09
CZ286077B6 (cs)	2000-01-12
CA2111607A1 (en)	1994-06-22
JPH06237790A (ja)	1994-08-30
IL108090A0 (en)	1994-04-12
AU5250293A (en)	1994-06-30
NZ250478A (en)	1995-03-28
US5914263A (en)	1999-06-22
TW381120B (en)	2000-02-01
ATE182367T1 (de)	1999-08-15
CZ286162B6 (cs)	2000-01-12
BG61511B1 (bg)	1997-10-31
CN1255496A (zh)	2000-06-07
ES2134241T3 (es)	1999-10-01
EP0605033A1 (en)	1994-07-06
IL108090A (en)	1998-10-30
PL301539A1 (en)	1994-06-27
DK0605033T3 (da)	2000-02-07
KR940014808A (ko)	1994-07-19
PL178517B1 (pl)	2000-05-31
FI935676A0 (fi)	1993-12-16
NO934652D0 (no)	1993-12-16
EP0939135A1 (en)	1999-09-01
RO112517B1 (ro)	1997-10-30
BG98305A (bg)	1994-07-29
EP0605033B1 (en)	1999-07-21
FI935676A7 (fi)	1994-06-22
RU2124506C1 (ru)	1999-01-10
DE69325698D1 (de)	1999-08-26
GR3031446T3 (en)	2000-01-31
NO934652L (no)	1994-06-22
CZ278493A3 (en)	1994-07-13
PL177831B1 (pl)	2000-01-31
AU674547B2 (en)	1997-01-02
DE69325698T2 (de)	2000-01-27

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