para-nitrobenzyl 7-(R)-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: para-nitrobenzyl 7-(R)-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate
• 英文别名: 4-nitrobenzyl 3-hydroxy-7-phenoxyacetamido-3-cephem-4-carboxylate；p-nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate；p-nitrobenzyl 3-hydroxy-7-phenoxyacetamido-3-cephem-4-carboxylate；p-Nitrobenzyl 3-hyroxy-7-phenoxyacetamido-3-cephem-4-carboxylate；(4-nitrophenyl)methyl (6R)-3-hydroxy-8-oxo-7-[(2-phenoxyacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• 化学式: C₂₂H₁₉N₃O₈S
• 分子量: 485.474
• InChiKey: MSJBRVIZZHKNPL-BDPMCISCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  176
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  para-nitrobenzyl 7-(R)-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate 、 异丙醚 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 生成 p-nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate-1, 1-dioxide
  参考文献：
  名称：

  Process for the stereospecific synthesis of keto-enol tautomeric mixture

  摘要：

  描述了一种用于立体特异性合成对硝基苄基(1R,6R,7R)-7-苯氧乙酰胺-3-氧代-3-头孢烯-4-(R/S)-羧酸酯-1-氧化物和对硝基苄基(1R,6R,7R)-7-苯氧乙酰胺-3-羟基-3-头孢烯-4-羧酸酯-1-氧化物的酮醇互变异构混合物的工艺。该工艺包括：a) 在惰性溶剂如丙酮或甲基乙基酮中，优选在质子溶剂如甲醇、乙酸或异丙醇存在下，于-90°C至-40°C的温度下，将对硝基苄基7-苯氧乙酰胺-3-亚甲基头孢烯-4-羧酸酯与臭氧反应，生成相应的臭氧化物；b) 无需使用任何还原剂，将臭氧化物分解为酮醇互变异构混合物，即对硝基苄基(1R,6R,7R)-7-苯氧乙酰胺-3-氧代-3-头孢烯-4-(R/S)-羧酸酯-1-氧化物和对硝基苄基(1R,6R,7R)-7-苯氧乙酰胺-3-羟基-3-头孢烯-4-羧酸酯-1-氧化物。这种酮醇互变异构混合物是合成头孢菌素类抗生素（如头孢克洛）的有价值的中间体。

  公开号：

  US05750683A1
• 作为产物：
  描述：

  p-Nitrobenzyl alpha-[4-mercapto-3-phenoxyacetamido-2-oxoazetidin-1-yl]-alpha-(2-bromo-1-hydroxyethylidene)acetate 在 silica gel 、 氯仿 作用下， 以 苯 为溶剂， 反应 1.0h， 以to give p-nitrobenzyl 3-hydroxy-7-phenoxyacetamido-3-cephem-4-carboxylate (60 mg)的产率得到para-nitrobenzyl 7-(R)-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate
  参考文献：
  名称：

  Cyclization to form cephem ring and intermediates therefor

  摘要：

  下列式子所代表的中间体，用于合成3-羟基-3-头孢烷类化合物。其中，A和B分别为氢或氨基取代基；R为氢或硫醇取代基；Hal为卤素；X为羟基或羧基保护基；A和R之间的断线表示当R和B为氢，A为羧酸酰基时，取代基可以结合形成氮杂环硫唑双环结构；以及其烯胺衍生物。

  公开号：

  US04332722A1

文献信息

• Certain 7-oxo-4-thio-2,6-diazabicyclo-3,2,0-hept-2-ene compounds
  申请人：Shionogi & Co., Ltd.

  公开号：US04079181A1

  公开（公告）日：1978-03-14

  An intermediate represented by following formula for synthesizing 3-hydroxy-3-cephem compounds. ##STR1## wherein A and B each is a hydrogen or amino substituent; R is a hydrogen or thiol substituent; Hal is a halogen; X is a hydroxy or carboxy protecting group; the broken line between A and R shows that when R and B are hydrogens, and A is a carboxylic acyl, the substituents can be combined to form an azetidinothiazoline bicyclic ring; and the enamine derivatives thereof.

  以下公式代表合成3-羟基-3-头孢菌素化合物的中间体。其中，A和B分别是氢或氨基取代基；R是氢或硫醇取代基；Hal是卤素；X是羟基或羧基保护基；在A和R之间的断线表示当R和B为氢，而A为羧酸酰基时，取代基可以结合形成氮杂环并噻唑啉双环；以及其烯胺衍生物。
• Cyclization to form cephem ring and intermediates therefor
  申请人：Shionogi & Co., Ltd.

  公开号：US04160085A1

  公开（公告）日：1979-07-03

  Intermediates represented by the following formulas are useful for synthesizing 3-hydroxy-3-cephem compounds ##STR1## wherein A and B each is a hydrogen or amino substituent; R is a hydrogen or thiol substituent; Hal is a halogen; X is a hydroxy or carboxy protecting group; the broken line between A and R shows that when R and B are hydrogens, and A is a carboxylic acyl, the substituents can be combined to form an azetidinothiazoline bicyclic ring; and the enamine derivatives thereof. One embodiment provides for cyclizing a compound of the formula: ##STR2## wherein A, B, X and Hal are as defined above, which comprises treating the said compound with an acid, base, or solvent if required in the presence of a catalyzer to give a compound represented by following formula ##STR3## In a further embodiment a compound represented by the following formula ##STR4## wherein A, B, R and X are as defined above, is prepared by a process which comprises treating an enamine of a compound represented by following formula ##STR5## wherein A, B, R, X, Hal and broken line are as defined above, with a disubstituted amino containing from 2 to 20 carbon atoms, with the action of an aqueous acid.

  以下式子代表的中间体在合成3-羟基-3-头孢烷化合物时非常有用：##STR1## 其中A和B均为氢或氨基取代基；R为氢或硫醇取代基；Hal为卤素；X为羟基或羧基保护基；A和R之间的断裂线表示当R和B为氢，A为羧酸酰基时，取代基可以结合形成氮杂环硫唑双环环；以及其烯胺衍生物。一种实施例提供了将以下式子的化合物环化：##STR2## 其中A、B、X和Hal如上所定义，包括在催化剂存在下，用酸、碱或必要的溶剂处理所述化合物，以给出以下式子所代表的化合物：##STR3## 在另一种实施例中，通过将以下式子所代表的烯胺与含有2至20个碳原子的二取代氨基化合物在水酸的作用下处理，制备出以下式子所代表的化合物：##STR4## 其中A、B、R和X如上所定义。
• Cyclization to form cephem ring and azetidinone intermediates therefor
  申请人：Shionogi & Co., Ltd.

  公开号：US04440683A1

  公开（公告）日：1984-04-03

  An intermediate represented by following formula for synthesizing 3-hydroxy-3-cephem compounds. ##STR1## wherein A and B each is a hydrogen or amine substituent; R is a hydrogen or thiol substituent; Nal is a halogen; X is a hydroxy or carboxy protecting group; the broken line between A and R shows that when R and B are hydrogens, and A is a carboxylic acyl, the substituents can be combined to form an azetidimethiazoline bicyclic ring; and the enamine derivatives thereof.

  以下公式代表合成3-羟基-3-头孢菌素类化合物的中间体。其中A和B分别为氢或胺基取代基；R为氢或硫醇取代基；Nal为卤素；X为羟基或羧基保护基；A和R之间的断线表示当R和B为氢，A为羧酸酰基时，取代基可以组合形成一种氮杂环庚烷-噻唑啉二环环。以及其烯胺衍生物。
• Preparation of 3-substituted cephalosporins
  申请人：Lilly Industries Limited

  公开号：US04301280A1

  公开（公告）日：1981-11-17

  There is described a process for preparing an enamine of formula (IX): ##STR1## where R.sup.2 is a carboxylic acid protecting group and R.sup.3 is the residue of a carboxylic acid derived acyl group and where R.sup.5 and R.sup.6 are the same or different C.sub.1-4 alkyl or C.sub.7-10 aralkyl groups; or taken together with the adjacent nitrogen atom form a heterocyclic ring containing from 4 to 8 carbon atoms and optionally a further heteroatom selected from oxygen and nitrogen; by reacting a compound of formula (XII): ##STR2## with an amine of formula HNR.sup.5 R.sup.6, the reactant of formula (XII) being prepared by reaction of an appropriate enol derivative with a phosphorus reagent. The enamines of formula (IX) are useful in the preparation of 3-hydroxycephalosporins.

  本发明描述了一种制备式（IX）的恩酰胺的过程：##STR1## 其中R.sup.2是羧酸保护基，R.sup.3是来自羧酸衍生的酰基残基，R.sup.5和R.sup.6是相同或不同的C.sub.1-4烷基或C.sub.7-10芳基烷基；或与相邻的氮原子结合形成含有4到8个碳原子和可选的进一步杂原子（选自氧和氮）的杂环环；通过将式（XII）的化合物：##STR2## 与式HNR.sup.5 R.sup.6的胺反应制备式（XII）的反应物，其中适当的烯醇衍生物与磷试剂反应制备。式（IX）的恩酰胺在3-羟基头孢菌素的制备中有用。
• Cephalosporin intermediates
  申请人：Eli Lilly and Company

  公开号：US04060688A1

  公开（公告）日：1977-11-29

  3-Exomethylenecepham and 3-hydroxy-3-cephem sulfoxides represented by the formulas ##STR1## wherein R is an acyl group derived from a carboxylic acid and R.sub.1 is a carboxylic acid protecting group, are useful intermediates in the synthesis of 3-alkoxy-3-cephem, 3-chloro-3-cephem and 3-methyl-3-cephem antibiotic compounds.

  3-Exomethylenecepham和3-羟基-3-头孢烷砜的化学式分别为##STR1##其中R是来自羧酸的酰基，R.sub.1是羧酸保护基，它们是合成3-烷氧基-3-头孢烷、3-氯-3-头孢烷和3-甲基-3-头孢烷抗生素化合物的有用中间体。