<6R<6α,7β(Z)>>-3-<<6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinyl>carbonyloxymethyl>-7-<(methoxyimino)<2-(triphenylmethyl)amino-4-thiazolyl>acetylamino>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxyli... | 139263-67-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: <6R<6α,7β(Z)>>-3-<<6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinyl>carbonyloxymethyl>-7-<(methoxyimino)<2-(triphenylmethyl)amino-4-thiazolyl>acetylamino>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxyli...
• 英文别名: [6R(6α,7β(Z))]-3-{[6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinyl]carbonyloxymethyl}-7-{(methoxyimino)[2-(triphenylmethyl)amino-4-thiazolyl]acetylamino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxyli...；(6R,7R)-3-[[6,8-difluoro-1-(2-fluoroethyl)-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carbonyl]oxymethyl]-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 139263-67-5
• 化学式: C₅₀H₄₅F₃N₈O₈S₂
• 分子量: 1007.08
• InChiKey: RTTIPFPRHJXNEL-OKQOTSBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  71
• 可旋转键数：
  17
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  240
• 氢给体数：
  3
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  <6R<6α,7β(Z)>>-3-<<6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinyl>carbonyloxymethyl>-7-<(methoxyimino)<2-(triphenylmethyl)amino-4-thiazolyl>acetylamino>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxyli... 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 3.0h， 以93%的产率得到<6R<6α,7β(Z)>>-7-<(2-amino-4-thiazolyl)(methoxyimino)acetylamino>-3-<<6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinyl>carbonyloxymethyl>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid bis..........
  参考文献：
  名称：

  Synthesis of a Dual-Action Cephalosporin: A Novel Approach to 3-Acyloxymethyl-3- cephems

  摘要：

  由 7-氨基头孢烷酸 (7-ACA)、S-苯并噻唑-2-基 (2-氨基-4-噻唑基)(甲氧亚氨基)硫代乙酸酯 (MAEM)和氟罗沙星[6,8-二氟-1-(2-氟乙基)-1,4-二氢-7-(4-甲基-1-哌嗪基)-4-氧代-3-喹啉羧酸，3]。原位制备的三苯甲基 MAEM 与 7-ACA 在二氯甲烷中偶联，然后水解乙酸基团，得到 3-羟甲基-3-cephem 2。发现这两种产物的比例取决于所使用的活化酯离去基团的性质，其中由氯甲酸环己酯制备的活化酯更有利于 4 的形成。除去三丁基后，就得到了双效头孢菌素 5。

  DOI：

  10.1055/s-1992-26326
• 作为产物：
  描述：

  氟罗沙星 、 <6R<6α,7β(Z)>>-3-(hydroxymethyl)-7-<(methoxyimino)<2-(triphenylmethyl)amino-4-thiazolyl>acetylamino>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid (1:1) tributylamine salt 在 4-二甲氨基吡啶 三正丁胺 、 氯甲酸环己酯 作用下， 生成 、 <6R<6α,7β(Z)>>-3-<<6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinyl>carbonyloxymethyl>-7-<(methoxyimino)<2-(triphenylmethyl)amino-4-thiazolyl>acetylamino>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxyli...
  参考文献：
  名称：

  Synthesis of a Dual-Action Cephalosporin: A Novel Approach to 3-Acyloxymethyl-3- cephems

  摘要：

  由 7-氨基头孢烷酸 (7-ACA)、S-苯并噻唑-2-基 (2-氨基-4-噻唑基)(甲氧亚氨基)硫代乙酸酯 (MAEM)和氟罗沙星[6,8-二氟-1-(2-氟乙基)-1,4-二氢-7-(4-甲基-1-哌嗪基)-4-氧代-3-喹啉羧酸，3]。原位制备的三苯甲基 MAEM 与 7-ACA 在二氯甲烷中偶联，然后水解乙酸基团，得到 3-羟甲基-3-cephem 2。发现这两种产物的比例取决于所使用的活化酯离去基团的性质，其中由氯甲酸环己酯制备的活化酯更有利于 4 的形成。除去三丁基后，就得到了双效头孢菌素 5。

  DOI：

  10.1055/s-1992-26326

文献信息

• A process for synthesizing cephalosporin compounds
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0453952A2

  公开（公告）日：1991-10-30

  A process for synthesizing cephalosporin compounds of the general formula    wherein R¹ is a quinolonyl or an azaquinolonyl group; R² is selected from the group consisting of hydrogen, lower alkoxy, amino, lower alkylthio and lower alkanoylamino; and R³ is selected from the group consisting of hydrogen and an acyl group, including the pharmaceutically acceptable salts, readily hydrolyzable esters thereof and hydrates of said compounds; said process comprising reacting a cephalosporin compound of the formula    wherein R² is selected from the group consisting of hydrogen, lower alkoxy, amino, lower alkylthio and lower alkanoylamino; R³ is selected from the group consisting of hydrogen and an acyl group; and Rb is an organic base which forms a salt with the 2-COOH substituent which salt is soluble in non-aqueous organic solvents, with an activated quinolone compound of formula    wherein R¹ is quinolonyl or an azaquinolonyl group; and Rf is alkyl, alkenyl, aryl which may be substituted or unsubstituted, cycloalkyl which may be substituted or unsubstituted, cycloalkenyl which may be substituted or unsubstituted or aralkyl, the reaction being carried out in a non-aqueous organic solvent in the presence of a reaction promoter, whereafter, (a) for the manufacture of a readily hydrolyzable ester of a compound of formula I a carboxylic acid of formula I is subjected to a corresponding esterification, or (b) for the manufacture of salts or hydrates of a compound of formula I or hydrates of said salts a compound of formula I is converted into a salt or hydrate or into a hydrate of said salt. The end products are antibacterially active.

  一种合成通式头孢菌素化合物的工艺 其中 R¹ 是喹啉基或偶氮喹啉基；R² 选自氢、低级烷氧基、氨基、低级烷硫基和低级烷酰氨基组成的组；以及 R³ 选自氢和酰基组成的组、 包括药学上可接受的盐、其易水解酯和所述化合物的水合物；所述工艺包括使式如下的头孢菌素化合物反应 其中 R² 选自氢、低级烷氧基、氨基、低级烷硫基和低级烷酰氨基组成的组；R³ 选自氢和酰基组成的组；Rb 是有机碱，它与 2-COOH 取代基形成盐，该盐可溶于非水有机溶剂、 式中的活化喹诺酮化合物 其中 R¹ 是喹啉基或偶氮喹啉基；Rf 是烷基、烯基、可取代或未取代的芳基、可取代或未取代的环烷基、可取代或未取代的环烯基或芳烷基、 该反应在非水有机溶剂中，在反应促进剂存在下进行，然后、 (a) 为制造式 I 化合物的易水解酯，将式 I 羧酸进行相应的酯化反应，或 (b) 为制造式 I 化合物的盐或水合物或所述盐的水合物，将式 I 化合物转化为盐或水合物或所述盐的水合物。 最终产品具有抗菌活性。
• US5066800A
  申请人：——

  公开号：US5066800A

  公开（公告）日：1991-11-19
• Synthesis of a Dual-Action Cephalosporin: A Novel Approach to 3-Acyloxymethyl-3- cephems
  作者：Masami Okabe、Ruen-Chu Sun

  DOI：10.1055/s-1992-26326

  日期：——

  A practical synthesis of the dual-action cephalosporin 5 from 7-aminocephalosporanic acid (7-ACA), S-benzothiazol-2-yl (2-amino-4-thiazolyl)(methoxyimino)thioacetate (MAEM), and fleroxacin [6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazi-nyl)-4-oxo-3-quinolinecarboxylic acid, 3] is described. Tritylated MAEM prepared in situ was coupled with 7-ACA in dichloromethane followed by hydrolysis of the acetate group to afford the 3-hydroxymethyl-3-cephem 2. The direct acylation of 2, which has an unprotected 4-carboxy group, with activated esters of 3 gave mixtures of the desired ester A (4) and the lactone B. The ratio of these two products was found to depend on the nature of the leaving group of the activated ester used, with the one prepared from cyclohexyl chloroformate favoring the formation of 4. Ester 4 was isolated in more than 50% overall yield from 7-ACA. Removal of the trityl group afforded the dual- action cephalosporin 5.

  由 7-氨基头孢烷酸 (7-ACA)、S-苯并噻唑-2-基 (2-氨基-4-噻唑基)(甲氧亚氨基)硫代乙酸酯 (MAEM)和氟罗沙星[6,8-二氟-1-(2-氟乙基)-1,4-二氢-7-(4-甲基-1-哌嗪基)-4-氧代-3-喹啉羧酸，3]。原位制备的三苯甲基 MAEM 与 7-ACA 在二氯甲烷中偶联，然后水解乙酸基团，得到 3-羟甲基-3-cephem 2。发现这两种产物的比例取决于所使用的活化酯离去基团的性质，其中由氯甲酸环己酯制备的活化酯更有利于 4 的形成。除去三丁基后，就得到了双效头孢菌素 5。