CN1212699A - 1(2h)喹啉羧酸的新衍生物、其制备方法和用于合成具有抗菌性产品的用途 - Google Patents
1(2h)喹啉羧酸的新衍生物、其制备方法和用于合成具有抗菌性产品的用途 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims description 10
- 239000000126 substance Substances 0.000 title abstract 3
- 230000003115 biocidal effect Effects 0.000 title abstract 2
- FLXFRSZKOVKKPQ-UHFFFAOYSA-N 1,2-dihydroquinoline-2-carboxylic acid Chemical class C1=CC=C2C=CC(C(=O)O)NC2=C1 FLXFRSZKOVKKPQ-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
- -1 cyclic acetal Chemical class 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000002585 base Substances 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical class CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 claims description 3
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 2
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 claims description 2
- RMBUDIJMMPDEBH-UHFFFAOYSA-N ethyl 1,2-dihydroquinoline-2-carboxylate Chemical compound C1=CC=C2C=CC(C(=O)OCC)NC2=C1 RMBUDIJMMPDEBH-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 2
- ZYXNAQRXUFIBIF-UHFFFAOYSA-N 4-[2-(1,3-dioxolan-2-yl)ethyl]quinoline Chemical group C=1C=NC2=CC=CC=C2C=1CCC1OCCO1 ZYXNAQRXUFIBIF-UHFFFAOYSA-N 0.000 claims 1
- PEUCOYOJQKOHNB-UHFFFAOYSA-N C(C)C1N(C2=CC=CC=C2C=C1)C(=O)O Chemical compound C(C)C1N(C2=CC=CC=C2C=C1)C(=O)O PEUCOYOJQKOHNB-UHFFFAOYSA-N 0.000 claims 1
- 101150058891 alc1 gene Proteins 0.000 abstract 1
- 101150117093 alc2 gene Proteins 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- VHAHTQAZZOWKGC-UHFFFAOYSA-N ethyl 2-diethoxyphosphoryl-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OCC)C(P(=O)(OCC)OCC)C=CC2=C1 VHAHTQAZZOWKGC-UHFFFAOYSA-N 0.000 description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- PPHVREYBYFPPHD-UHFFFAOYSA-N 2-ethylquinoline;hydrochloride Chemical compound Cl.C1=CC=CC2=NC(CC)=CC=C21 PPHVREYBYFPPHD-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-SOOFDHNKSA-N D-ribopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@@H]1O SRBFZHDQGSBBOR-SOOFDHNKSA-N 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- ANUZKYYBDVLEEI-UHFFFAOYSA-N butane;hexane;lithium Chemical compound [Li]CCCC.CCCCCC ANUZKYYBDVLEEI-UHFFFAOYSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen 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
- 239000002994 raw material Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/60—Quinoline or hydrogenated quinoline ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
公开了式(Ⅰ)所示的化合物,其中各个alc1、alc2和alc3可以相同或不同,是含至多8个碳原子的烷基,n是0—8的整数,R1和R2是含至多8个碳原子的O－烷基,或与它们所连接的碳原子一起形成一个环状缩醛。这类化合物可用于制备适用于合成抗菌素的物质。
Description
本发明涉及1(2H)喹啉羧酸的新衍生物、其制备方法和用于合成具有抗菌性产品的用途。
本发明的一个主题是式(Ⅰ)的化合物：
其中alc1、alc2和alc3可以相同或互不相同，代表含最多8个碳原子的烷基，n代表0-8的整数，R1和R2代表含最多8个碳原子的O-烷基，或与它们所连接的碳原子一起形成一个环状的缩醛。
烷基较好是甲基、乙基、正丙基、异丙基、丁基、异丁基或叔丁基。
当R1和R2与它们所连接的碳原子一起形成环状的缩醛时，它较好是1个下式的基团：
其中P代表数1、2、3或4。
本发明的一个非常具体的主题是式(Ⅰ)的化合物，其中n代表2，且其中alc1、alc2和alc3代表乙基。
在本发明的优选化合物中，可以提及的是如下定义的式(Ⅰ)化合物，其中R1和R2与它们所连接的碳原子一起形成一个1,3-二氧杂环戊烷基：
或1,3-二氧杂环己烷基：
本发明的一个非常具体的主题是式(Ⅰ)化合物，其制备方法在后面实验部分给出。
本发明的主题也是式(Ⅰ)化合物的制备方法，其特征在于使式(Ⅱ)的化合物：
式中alc1、alc2和alc3保留其前面的含义，经受式(Ⅲ)化合物的作用，以得到相应的式(Ⅰ)化合物：
式中Hal代表卤原子，R1、R2和n保留其前面的含义。
用作本发明方法起始材料的式(Ⅱ)化合物可按Tetrah.Lett.23(16),1709-12(1982)或日本专利申请1221-102中所述方法制备。
在本发明方法的一个优选的实施方案中，Hal是溴原子或氯原子。
本发明的一个具体主题是一种方法，其特征在于该方法的操作是在一种强碱存在下进行的。
所用的碱是丁基锂，或碱金属或碱土金属的醇盐，例如锂、钠，或钾的叔丁醇盐或叔戊醇盐，或者还有氢氧化锂。优先使用钠或钾的叔丁醇盐或叔戊醇盐。
此外，本发明的一个主题是用途，其特征在于使式(Ⅰ)化合物经受强碱的作用，以得到相应的式(Ⅳ)化合物：
其中n、R1和R2保留其前述的含义。
本发明的一个更具体的主题是用途，其特征在于所述强碱可以是苏打，或优选乙醇钠。
该操作也可以在碱金属碘化物如碘化钠存在下，在非质子传递极性溶剂中在高温下进行。
有利的是，且具体地说，当R1和R2与它们所连接的碳原子一起形成一个环状缩醛时，式(Ⅳ)的产物以盐酸盐的形式精制，但它也可以呈该醛的水合物形式。
本发明的一个更具体的主题是实验部分所述的实例1或2的化合物用于制备式(Ⅳ)产物的用途。
式(Ⅳ)化合物通常是已知产品；它们也可以按照欧洲专利申请676409所述方法制备。
式(Ⅳ)化合物可以转化成相应的醛：
然后按照上面提到的专利申请中所述方法转化成具有抗菌性的产品。
由此可见，以实验部分中所述应用的产品为原料，可以制得11,12-二脱氧-3-脱[(2,6-二脱氧-3-C-甲基-3-O甲基-α-L-己糖吡喃核糖基(ribohexopyranosyl))氧]-6-O-甲基-3-氧代-12,11-(氧羰基(2-(3-(4-喹啉基)丙基)亚肼基))-红霉素，如前面提到的欧洲专利申请所指出的那样，该化合物是一种具有有用的抗菌性的产品。
下列实例说明本发明，但又不限制本发明。
实例1
2-(二乙氧基氧膦基)4-(2-(1,3-二氧杂环戊烷-2-基)乙基-1(2H)-喹啉羧酸乙酯
在-78℃将75ml 1.6M的正丁基锂己烷溶液加入到33.933g 2-(二乙氧基氧膦基)-1(2H)-喹啉羧酸乙酯在500ml四氢呋喃中的溶液中。接着加入18ml 2-(2-溴乙基)-1,3二氧杂环戊烷。让反应介质回到环境温度，然后在搅拌下维持5小时。加入300ml水，接着搅拌并倾析。有机相用水洗涤、干燥，然后过滤并除去溶剂。得到63.45g产物，用色谱法将其提纯，用乙酸乙酯洗脱。由此制得所希望的产物。
Rf=0.16，收率62.7％
NMR CDCl3 ppm
0.97(t),N-COOEt中的CH3；1.18(t)-1.33(t),P-OEt中的CH3；1.91(m)(2H),CH-CH2-CH2；2.60(m)(2H),=C-CH2-CH2；-3.70至4.40(～11H),P-OEt和COOEt中的CH2，缩酮中的O-CH2；4.96(t)(1H),O-CH-CH2；5.52(wd)(1H),P-CH-N；5.90(wt),H3；7.11(m)(1H),7.20至7.35(m)(2H)。
应用1：
4-(2-(1,3-二氧杂环戊烷-2-基)乙基-喹啉
在氮气保护下将含有63.45g实例1中制得的产物、430ml 2N苏打溶液和430ml绝对乙醇的混合物加热回流1小时。
除去乙醇后用异丙醚进行萃取。有机相用水洗涤、干燥并过滤。(收率=43％)。蒸出溶剂后得到11.263g产物，将该产物进行硅胶柱色谱提纯，用70-30乙酸乙酯-环己烷混合物洗脱。得到所希望的产物。Rf=0.4NMR CDCl3 ppm2.13(m)，中心-CH2-；3.22(m),=C-CH2-CH2；3.86至4.11(m),-O-CH2-CH2-O-；5.00(t),O-CH(缩酮)；7.27(d,j=4.5)H3；8.81(d,j=4.5)H2；7.57(dt)和7.71(dt),H6和H7；8.10(m,2H),H5和H8。
实例2
2-(二乙氧基氧膦基)4-(2-(1,3-二噁烷-2-基)乙基)1(2H)-喹啉羧酸乙酯
在20°±2℃将3.6g叔丁醇钾加入到含有9g 2-(二乙氧基氧膦基)1(2H)-喹啉羧酸乙酯和45ml二甲基甲酰胺的溶液中。反应介质在搅拌下保持30分钟。然后在-20°±2℃加入9.7g 2(2-碘乙基)-1,3-二噁烷。加入54ml水，将所得溶液倒入到180ml水中，用异丙醚进行萃取，接着用水洗涤，干燥后再用异丙醚洗涤、萃取物在减压下浓缩，以便得到12g所希望的产物。
应用2
4-(2-(1,3-二噁烷-2-基)乙基喹啉盐酸盐
在20°±2℃将7.5g乙醇钠引入到含有10g实例1或2制备的产物和50ml乙醇100的溶液中。将所得混合物回流1小时，接着冷却至20°±2℃，然后维持搅拌1.5小时。在减压下进行蒸馏后，在20°±2℃加入50ml水。用异丙醚进行萃取，接着用水洗涤，用硫酸钠干燥，分离后用异丙醚洗涤。浓缩后得到3.89g碱形式的所需产物。将3.76g所得产物溶于19ml乙酸乙酯中制成20℃的溶液，在20分钟内加入7.6ml含10％盐酸的乙酸乙酯溶液，反应介质在搅拌下保持1小时，然后过滤，沉淀物用乙酸乙酯洗涤，在40℃干燥2小时后，得到2.56g预期的盐酸盐。
Claims (12)
1．式(Ⅰ)的化合物：
其中alc1、alc2和alc3可以相同或互不相同，代表含最多8个碳原子的烷基，n代表0-8的整数，R1和R2代表含最多8个碳原子的O-烷基，或与它们所连接的碳原子一起形成一个环状的缩醛。
2．如权利要求1所定义的式(Ⅰ)化合物，其中n代表2。
3．如权利要求1或2所定义的式(Ⅰ)化合物，其中alc1、alc2和alc3代表乙基。
4．如权利要求1-3中任何一项所定义的式(Ⅰ)化合物，其中R1和R2与它们所连接的碳原子一起形成一个1,3-二氧杂环戊烷基：或1,3二氧杂环己烷基：
5．如权利要求1所定义的式(Ⅰ)化合物，其名称如下：
-2-(二乙氧基氧膦基)4-(2(1,3-二氧杂环戊烷-2-基)乙基-1(2H)-喹啉羧酰乙酯，
-2-(二乙氧基氧膦基)4-(2-(1,3-二噁烷-2-基)乙基)1(2H)-喹啉羧酸乙酯。
6．如权利要求1-5中任何一项所定义的式(Ⅰ)化合物的制备方法，其特征在于使式(Ⅱ)的化合物：
式中alc1、alc2和alc3保留其前面的含义，经受式(Ⅲ)化合物的作用，以得到相应的式(Ⅰ)化合物；
式中Hal代表卤原子，R1、R2和n保留其前面的含义。
7．按照权利要求6的方法，其特征在于该操作是在强碱存在下进行的。
8．按照权利要求7的方法，其特征在于所用的碱是钠或钾的叔丁醇盐或叔戊醇盐。
9．如权利要求1-5中任何一项所定义的式(Ⅰ)化合物的用途，其特征在于使式(Ⅰ)化合物经受强碱的作用，以制得相应的式(Ⅳ)化合物：式中n、R1和R2保留其前面的含义。
10．按照权利要求9的用途，其特征在于所述强碱是乙醇钠。
11．按照权利要求9或10的用途，其特征在于所用的式(Ⅰ)产物是按照权利要求5的2-(二乙氧基氧膦基)-4-(2-(1,3-二氧杂环戊烷-2-基)乙基-1(2H)-喹啉羧酰乙酯，而所制备的式(Ⅳ)产物是4-(2-(1,3-二氧杂环戊烷-2-基)乙基)-喹啉。
12．按照权利要求9或10的用途，其特征在于所用的式(Ⅰ)产物是按照权利要求5的2(二乙氧基氧膦基)4-(2-(1,3-二噁烷2基)乙基)1(2H)-喹啉羧酸乙酯，而所制备的式(Ⅳ)产物是4-(2-(1,3-二噁烷-2-基)乙基)-喹啉。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9602473A FR2745289B1 (fr) | 1996-02-28 | 1996-02-28 | Nouveaux derives de l'acide 1(2h) quinoleine carboxylique, leur procede de preparation et leur application a la synthese de produits doues de proprietes antibiotiques |
| FR96/02473 | 1996-02-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1212699A true CN1212699A (zh) | 1999-03-31 |
| CN1072226C CN1072226C (zh) | 2001-10-03 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97192624A Expired - Fee Related CN1072226C (zh) | 1996-02-28 | 1997-02-27 | 1(2h)喹啉羧酸的衍生物、其制备方法和用于合成具有抗菌性产品的用途 |
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| Country | Link |
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| US (1) | US6002006A (zh) |
| EP (1) | EP0885232B1 (zh) |
| JP (1) | JP3856241B2 (zh) |
| KR (1) | KR19990087323A (zh) |
| CN (1) | CN1072226C (zh) |
| AT (1) | ATE231153T1 (zh) |
| AU (1) | AU708022B2 (zh) |
| BR (1) | BR9707777A (zh) |
| CA (1) | CA2247172C (zh) |
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| DE (1) | DE69718444T2 (zh) |
| DK (1) | DK0885232T3 (zh) |
| EA (1) | EA001157B1 (zh) |
| ES (1) | ES2186871T3 (zh) |
| FR (1) | FR2745289B1 (zh) |
| HU (1) | HUP9900937A3 (zh) |
| IL (1) | IL125873A (zh) |
| NO (1) | NO983956D0 (zh) |
| NZ (1) | NZ331599A (zh) |
| OA (1) | OA10846A (zh) |
| PL (1) | PL185497B1 (zh) |
| PT (1) | PT885232E (zh) |
| SK (2) | SK284016B6 (zh) |
| TR (1) | TR199801708T2 (zh) |
| UA (1) | UA61069C2 (zh) |
| WO (1) | WO1997031926A1 (zh) |
| YU (1) | YU37198A (zh) |
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| AU2018255283B2 (en) * | 2017-04-17 | 2022-05-26 | Ohio State Innovation Foundation | Type II topoisomerase inhibitors and methods of making and using thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61221192A (ja) * | 1985-03-27 | 1986-10-01 | Toyo Soda Mfg Co Ltd | ホスホナ−ト誘導体 |
| FR2718450B1 (fr) * | 1994-04-08 | 1997-01-10 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments. |
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