CA1116618A - Antibiotiques a base d'azetidin-2-one a substitution - Google Patents

Antibiotiques a base d'azetidin-2-one a substitution

Info

Publication number: CA1116618A
Authority: CA; Canada
Prior art keywords: alpha; formula; acetoxyazetidin; group; amino
Prior art date: 1976-12-23
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.): Expired

Application number

CA000293769A

Other languages

English (en)

Inventor

Robin D.G. Cooper

Gary A. Koppel

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.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1976-12-23

Filing date

1977-12-22

Publication date

1982-01-19

1977-11-30 Priority claimed from US05/855,841 external-priority patent/US4144232A/en

1977-12-22 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1982-01-19 Application granted granted Critical

1982-01-19 Publication of CA1116618A publication Critical patent/CA1116618A/fr

Status Expired legal-status Critical Current

Links

229940088710 antibiotic agent Drugs 0.000 title abstract description 10
239000003242 anti bacterial agent Substances 0.000 title abstract description 8
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 39
238000000034 method Methods 0.000 claims abstract description 31
-1 cyanomethyl Chemical group 0.000 claims description 131
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 61
229910052739 hydrogen Inorganic materials 0.000 claims description 40
239000001257 hydrogen Substances 0.000 claims description 38
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
150000002431 hydrogen Chemical class 0.000 claims description 31
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
230000007062 hydrolysis Effects 0.000 claims description 23
238000006460 hydrolysis reaction Methods 0.000 claims description 23
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 claims description 22
125000001309 chloro group Chemical group Cl* 0.000 claims description 19
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 19
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 16
150000002923 oximes Chemical class 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
238000010438 heat treatment Methods 0.000 claims description 12
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
229910006069 SO3H Inorganic materials 0.000 claims description 8
150000001408 amides Chemical class 0.000 claims description 8
125000003277 amino group Chemical group 0.000 claims description 8
RWBFLRQNMJQDFQ-UHFFFAOYSA-N azetidin-2-one;1,3-thiazolidine Chemical compound C1CSCN1.O=C1CCN1 RWBFLRQNMJQDFQ-UHFFFAOYSA-N 0.000 claims description 8
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 7
125000000335 thiazolyl group Chemical group 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical compound OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 0.000 claims description 6
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 5
238000007796 conventional method Methods 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000000842 isoxazolyl group Chemical group 0.000 claims description 4
125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
125000005997 bromomethyl group Chemical group 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 3
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 3
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical group O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 3
125000001786 isothiazolyl group Chemical group 0.000 claims description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000002971 oxazolyl group Chemical group 0.000 claims description 3
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 2
239000003125 aqueous solvent Substances 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims description 2
HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 2
239000000126 substance Substances 0.000 claims 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
OHZZTXYKLXZFSZ-UHFFFAOYSA-I manganese(3+) 5,10,15-tris(1-methylpyridin-1-ium-4-yl)-20-(1-methylpyridin-4-ylidene)porphyrin-22-ide pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Mn+3].C1=CN(C)C=CC1=C1C(C=C2)=NC2=C(C=2C=C[N+](C)=CC=2)C([N-]2)=CC=C2C(C=2C=C[N+](C)=CC=2)=C(C=C2)N=C2C(C=2C=C[N+](C)=CC=2)=C2N=C1C=C2 OHZZTXYKLXZFSZ-UHFFFAOYSA-I 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 17
239000000543 intermediate Substances 0.000 abstract description 8
241000894006 Bacteria Species 0.000 abstract description 3
230000000844 anti-bacterial effect Effects 0.000 abstract description 3
244000052769 pathogen Species 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
239000000047 product Substances 0.000 description 47
239000000243 solution Substances 0.000 description 41
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 33
239000011541 reaction mixture Substances 0.000 description 31
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 13
150000002148 esters Chemical class 0.000 description 13
239000000203 mixture Substances 0.000 description 13
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
230000010933 acylation Effects 0.000 description 11
238000005917 acylation reaction Methods 0.000 description 11
125000004185 ester group Chemical group 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
125000000217 alkyl group Chemical group 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
125000000896 monocarboxylic acid group Chemical group 0.000 description 9
239000007858 starting material Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000003782 beta lactam antibiotic agent Substances 0.000 description 7
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
230000000903 blocking effect Effects 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
238000006722 reduction reaction Methods 0.000 description 6
229960001407 sodium bicarbonate Drugs 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
239000002904 solvent Substances 0.000 description 6
229930186147 Cephalosporin Natural products 0.000 description 5
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
229930182555 Penicillin Natural products 0.000 description 5
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
125000004442 acylamino group Chemical group 0.000 description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
229940124587 cephalosporin Drugs 0.000 description 5
150000001780 cephalosporins Chemical class 0.000 description 5
239000006260 foam Substances 0.000 description 5
229960000443 hydrochloric acid Drugs 0.000 description 5
235000011167 hydrochloric acid Nutrition 0.000 description 5
125000002950 monocyclic group Chemical group 0.000 description 5
239000002002 slurry Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
238000004809 thin layer chromatography Methods 0.000 description 5
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
239000002585 base Substances 0.000 description 4
239000012267 brine Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000010828 elution Methods 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
238000010992 reflux Methods 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 3
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 3
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
239000004342 Benzoyl peroxide Substances 0.000 description 3
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
UKAUYVFTDYCKQA-GSVOUGTGSA-N D-homoserine Chemical compound OC(=O)[C@H](N)CCO UKAUYVFTDYCKQA-GSVOUGTGSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
230000006181 N-acylation Effects 0.000 description 3
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
235000019400 benzoyl peroxide Nutrition 0.000 description 3
230000003115 biocidal effect Effects 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
238000005947 deacylation reaction Methods 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229930189801 nocardicin Natural products 0.000 description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
150000002960 penicillins Chemical class 0.000 description 3
AMLFJZRZIOZGPW-UHFFFAOYSA-N prop-1-en-1-amine Chemical compound CC=CN AMLFJZRZIOZGPW-UHFFFAOYSA-N 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
WTMSOAXMVMQIPY-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-(4-hydroxyphenyl)-2-oxoacetate Chemical compound C1=CC(O)=CC=C1C(=O)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 WTMSOAXMVMQIPY-UHFFFAOYSA-N 0.000 description 2
OCQICQZUUHJWGZ-UHFFFAOYSA-N 2,2-Dimethylthiazolidine-4-Carboxylic Acid Chemical compound CC1(C)NC(C(O)=O)CS1 OCQICQZUUHJWGZ-UHFFFAOYSA-N 0.000 description 2
KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 2
ZTNRUDZRCMWXPD-UHFFFAOYSA-N 3-benzoyl-2,2-dimethyl-1,3-thiazolidine-4-carboxylic acid Chemical compound CC1(C)SCC(C(O)=O)N1C(=O)C1=CC=CC=C1 ZTNRUDZRCMWXPD-UHFFFAOYSA-N 0.000 description 2
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 2
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 2
125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 2
239000004201 L-cysteine Substances 0.000 description 2
235000013878 L-cysteine Nutrition 0.000 description 2
DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical compound OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000001266 acyl halides Chemical class 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
239000000463 material Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
229910052700 potassium Chemical group 0.000 description 2
239000011591 potassium Chemical group 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000725 suspension Substances 0.000 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 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
239000011701 zinc Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
FAFRSCWDXJHQGG-UHFFFAOYSA-N (2-oxoazetidin-1-yl) acetate Chemical compound CC(=O)ON1CCC1=O FAFRSCWDXJHQGG-UHFFFAOYSA-N 0.000 description 1
KTIXRADTIPRGDB-UHFFFAOYSA-N (3-amino-4-oxoazetidin-2-yl) acetate Chemical class CC(=O)OC1NC(=O)C1N KTIXRADTIPRGDB-UHFFFAOYSA-N 0.000 description 1
NPRIAURNKLOSDM-UHFFFAOYSA-N (4-methoxyphenyl)methyl 2-amino-2-(3-chloro-4-hydroxyphenyl)acetate Chemical compound ClC=1C=C(C(N)C(=O)OCC2=CC=C(C=C2)OC)C=CC=1O NPRIAURNKLOSDM-UHFFFAOYSA-N 0.000 description 1
BHSLRJFNYLEJGK-UHFFFAOYSA-N (4-methoxyphenyl)methyl 2-amino-2-phenylacetate Chemical compound C1=CC(OC)=CC=C1COC(=O)C(N)C1=CC=CC=C1 BHSLRJFNYLEJGK-UHFFFAOYSA-N 0.000 description 1
QYAPHLRPFNSDNH-MRFRVZCGSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O QYAPHLRPFNSDNH-MRFRVZCGSA-N 0.000 description 1
ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
MGUQYZSKPMBDBI-UHFFFAOYSA-N 1,2,3,5a,6,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound N1CCC=CC2CCCCN21 MGUQYZSKPMBDBI-UHFFFAOYSA-N 0.000 description 1
125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 description 1
125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 description 1
125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 1
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
AIOMGEMZFLRFJE-UHFFFAOYSA-N 1,3-thiazolidine-4-carboxamide Chemical compound NC(=O)C1CSCN1 AIOMGEMZFLRFJE-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
GIGRWGTZFONRKA-UHFFFAOYSA-N 1-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CBr)C=C1 GIGRWGTZFONRKA-UHFFFAOYSA-N 0.000 description 1
BZNVHVGXOIASSU-UHFFFAOYSA-N 2,2,2-trichloroethyl 2-amino-2-(3,4-dichlorophenyl)acetate Chemical compound ClC=1C=C(C(N)C(=O)OCC(Cl)(Cl)Cl)C=CC=1Cl BZNVHVGXOIASSU-UHFFFAOYSA-N 0.000 description 1
APFVVGHEWFDTHM-UHFFFAOYSA-N 2,2,2-trichloroethyl 2-amino-2-phenylacetate Chemical compound NC(C1=CC=CC=C1)C(=O)OCC(Cl)(Cl)Cl APFVVGHEWFDTHM-UHFFFAOYSA-N 0.000 description 1
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
DJTOYFIIRMBOTM-UHFFFAOYSA-N 2-amino-4-(4-oxalophenoxy)butanoic acid Chemical compound OC(=O)C(N)CCOC1=CC=C(C(=O)C(O)=O)C=C1 DJTOYFIIRMBOTM-UHFFFAOYSA-N 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
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LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
229910014033 C-OH Inorganic materials 0.000 description 1
125000006519 CCH3 Chemical group 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
208000035473 Communicable disease Diseases 0.000 description 1
229910014570 C—OH Inorganic materials 0.000 description 1
QJPWUUJVYOJNMH-GSVOUGTGSA-N D-homoserine lactone Chemical compound N[C@@H]1CCOC1=O QJPWUUJVYOJNMH-GSVOUGTGSA-N 0.000 description 1
FFEARJCKVFRZRR-SCSAIBSYSA-N D-methionine Chemical compound CSCC[C@@H](N)C(O)=O FFEARJCKVFRZRR-SCSAIBSYSA-N 0.000 description 1
229930182818 D-methionine Natural products 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
241000147019 Enterobacter sp. Species 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
HHLFWLYXYJOTON-UHFFFAOYSA-N Glyoxylic acid Natural products OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
241000588748 Klebsiella Species 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
241000588769 Proteus <enterobacteria> Species 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
208000036366 Sensation of pressure Diseases 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
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241000607720 Serratia Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
241000534944 Thia Species 0.000 description 1
WREBNDYJJMUWAO-LWYYNNOASA-N [(1r,4ar,4br,10ar)-1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)[C@@H](CCC(C(C)C)=C3)C3=CC[C@H]21 WREBNDYJJMUWAO-LWYYNNOASA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001263 acyl chlorides Chemical class 0.000 description 1
238000013019 agitation Methods 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
239000011324 bead Substances 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
CDVFJAIXFABLSQ-UHFFFAOYSA-N benzyl 2-(4-methoxyanilino)acetate Chemical compound C1=CC(OC)=CC=C1NCC(=O)OCC1=CC=CC=C1 CDVFJAIXFABLSQ-UHFFFAOYSA-N 0.000 description 1
HFBVAYJGIAUFLM-UHFFFAOYSA-N benzyl 2-(6-bicyclo[3.2.0]heptanyl)acetate Chemical compound C(C1=CC=CC=C1)OC(CC1C2CCCC2C1)=O HFBVAYJGIAUFLM-UHFFFAOYSA-N 0.000 description 1
JRKMSIBQRCYECU-UHFFFAOYSA-N benzyl 2-amino-2-(3,4-dimethylphenyl)acetate Chemical compound CC=1C=C(C(N)C(=O)OCC2=CC=CC=C2)C=CC=1C JRKMSIBQRCYECU-UHFFFAOYSA-N 0.000 description 1
RWZSHYYCEWSCEJ-UHFFFAOYSA-N benzyl 2-amino-2-(4-aminophenyl)acetate Chemical compound C=1C=C(N)C=CC=1C(N)C(=O)OCC1=CC=CC=C1 RWZSHYYCEWSCEJ-UHFFFAOYSA-N 0.000 description 1
ABOKXMHXPAYKSU-UHFFFAOYSA-N benzyl 2-amino-2-(4-chlorophenyl)acetate Chemical compound ClC1=CC=C(C(N)C(=O)OCC2=CC=CC=C2)C=C1 ABOKXMHXPAYKSU-UHFFFAOYSA-N 0.000 description 1
JPQIAKOVZUIGCU-UHFFFAOYSA-N benzyl 2-amino-2-(4-hydroxyphenyl)acetate Chemical compound C=1C=C(O)C=CC=1C(N)C(=O)OCC1=CC=CC=C1 JPQIAKOVZUIGCU-UHFFFAOYSA-N 0.000 description 1
VNBZYMVEHPBBJM-UHFFFAOYSA-N benzyl 2-amino-2-phenylacetate Chemical compound C=1C=CC=CC=1C(N)C(=O)OCC1=CC=CC=C1 VNBZYMVEHPBBJM-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
150000001721 carbon Chemical class 0.000 description 1
125000006364 carbonyl oxy methylene group Chemical group [H]C([H])([*:2])OC([*:1])=O 0.000 description 1
150000003857 carboxamides Chemical class 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
238000002983 circular dichroism Methods 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
JSYGRUBHOCKMGQ-UHFFFAOYSA-N dichloramine Chemical compound ClNCl JSYGRUBHOCKMGQ-UHFFFAOYSA-N 0.000 description 1
125000004188 dichlorophenyl group Chemical group 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
LTLCGIKWGSDBMN-UHFFFAOYSA-L dimercury diacetate Chemical compound CC(=O)O[Hg][Hg]OC(C)=O LTLCGIKWGSDBMN-UHFFFAOYSA-L 0.000 description 1
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
235000019441 ethanol Nutrition 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012847 fine chemical Substances 0.000 description 1
239000012634 fragment Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
150000004676 glycans Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 description 1
125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 1
125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 description 1
150000002545 isoxazoles Chemical class 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
150000002731 mercury compounds Chemical class 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 description 1
244000000010 microbial pathogen Species 0.000 description 1
244000005700 microbiome Species 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
KXFJZKUFXHWWAJ-UHFFFAOYSA-N p-hydroxybenzoylformic acid Natural products OC(=O)C(=O)C1=CC=C(O)C=C1 KXFJZKUFXHWWAJ-UHFFFAOYSA-N 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
150000005331 phenylglycines Chemical class 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
150000003527 tetrahydropyrans Chemical group 0.000 description 1
125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
125000006004 trihaloethyl group Chemical group 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/085—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a nitrogen atom directly attached in position 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/04—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D277/06—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Cephalosporin Compounds (AREA)

CA000293769A 1976-12-23 1977-12-22 Antibiotiques a base d'azetidin-2-one a substitution Expired CA1116618A (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US75398076A	1976-12-23	1976-12-23
US753,980		1976-12-23
US855,841		1977-11-30
US05/855,841 US4144232A (en)	1976-12-23	1977-11-30	Substituted azetidin-2-one antibiotics

Publications (1)

Publication Number	Publication Date
CA1116618A true CA1116618A (fr)	1982-01-19

Family

ID=27115854

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000293769A Expired CA1116618A (fr)	1976-12-23	1977-12-22	Antibiotiques a base d'azetidin-2-one a substitution

Country Status (9)

Country	Link
JP (1)	JPS5392756A (fr)
CA (1)	CA1116618A (fr)
DE (1)	DE2757083A1 (fr)
ES (1)	ES465358A1 (fr)
FR (1)	FR2375209A1 (fr)
GB (1)	GB1591110A (fr)
IE (1)	IE46280B1 (fr)
IL (1)	IL53663A (fr)
NL (1)	NL7714157A (fr)

1977
- 1977-12-20 NL NL7714157A patent/NL7714157A/xx not_active Application Discontinuation
- 1977-12-20 GB GB52882/77A patent/GB1591110A/en not_active Expired
- 1977-12-21 IL IL53663A patent/IL53663A/xx unknown
- 1977-12-21 DE DE19772757083 patent/DE2757083A1/de not_active Withdrawn
- 1977-12-22 CA CA000293769A patent/CA1116618A/fr not_active Expired
- 1977-12-22 FR FR7738902A patent/FR2375209A1/fr active Granted
- 1977-12-22 ES ES465358A patent/ES465358A1/es not_active Expired
- 1977-12-22 IE IE2612/77A patent/IE46280B1/en unknown
- 1977-12-23 JP JP15634077A patent/JPS5392756A/ja active Pending

Also Published As

Publication number	Publication date
IL53663A (en)	1981-10-30
FR2375209A1 (fr)	1978-07-21
IE46280B1 (en)	1983-04-20
IE46280L (en)	1978-06-23
IL53663A0 (en)	1978-03-10
JPS5392756A (en)	1978-08-15
DE2757083A1 (de)	1978-07-06
NL7714157A (nl)	1978-06-27
GB1591110A (en)	1981-06-17
ES465358A1 (es)	1979-01-01
FR2375209B1 (fr)	1981-05-29

Legal Events

Date	Code	Title	Description
1999-01-19	MKEX	Expiry

Publication	Publication Date	Title
US4144232A (en)	1979-03-13	Substituted azetidin-2-one antibiotics
US4337197A (en)	1982-06-29	O-sulfated β-lactam hydroxamic acids and intermediates
SE457256B (sv)	1988-12-12	1-sulfo-2-oxazetidinderivat med antimikrobiella och beta-laktamasinhiberande egenskaper, foerfarande foer framstaellning daerav samt farmaceutisk komposition daerav
BG98723A (en)	1995-03-31	Cephalosporines
JPS6139313B2 (fr)	1986-09-03
PL94934B1 (fr)	1977-09-30
CA1109859A (fr)	1981-09-29	Derives de thiooxime de cephalosporine et de penicilline
US4533660A (en)	1985-08-06	Antibacterial O-sulfated β-lactam hydroxamic acids
US4241050A (en)	1980-12-23	Penam 1,1-dioxides as beta-lactamase inhibitors
US4122086A (en)	1978-10-24	Isopenicillins
CA1116618A (fr)	1982-01-19	Antibiotiques a base d'azetidin-2-one a substitution
CA1212378A (fr)	1986-10-07	ACIDE 1,1-DIOXO 2-.beta.-SUBSTITUTION-2-.alpha.-METHYL- (5R) PENAM-3-ALPHACARBOXYLIQUE, INHIBITEUR DE LA .beta.-LACTAMASE, ET PRODUITS INTERMEDIAIRES
US4166816A (en)	1979-09-04	Methods and intermediates for preparing cis-4-oxoazetidine intermediates
US4388316A (en)	1983-06-14	Amino-substituted oxazole, oxadiazole and isoxazole-substituted cephalosporins
US4203896A (en)	1980-05-20	Acetoxy azetidin-2-one antibiotics via thiazolidine ring cleavage
JPH0515692B2 (fr)	1993-03-02
FR2511375A1 (fr)	1983-02-18	Nouveaux derives de la cephalosporine, leur preparation et les medicaments qui les contiennent
EP0001715A2 (fr)	1979-05-02	Antibiotiques dérivés d'azétidinone et leurs préparations pharmaceutiques et utilisation
SE444682B (sv)	1986-04-28	Nya 7alfa-metoxicefalosporiner
US4072674A (en)	1978-02-07	Cis-4-oxoazetidine intermediates and methods of preparing them
US4144333A (en)	1979-03-13	Monocyclic beta-lactams with antibacterial activity
US4310459A (en)	1982-01-12	Process for producing carbamoyl substituted penams and carbamoyl substituted cephams from penicillin sulfoxide esters
US4831130A (en)	1989-05-16	β-lactam antibacterial agents
US4131734A (en)	1978-12-26	7β-Acyloxy-3-heterocyclicthiomethyl cephalosporins
US4581352A (en)	1986-04-08	Thienothienylglycyl cephalosporin derivatives