diphenylmethyl 3-hydroxy-2-<(3R,4R)-2-oxo-3-(phenoxyacetylamino)-4-(p-tolylsulfonylthio)-1-azetidinyl>-2-butenoate | 57561-96-3

• 英文名称: diphenylmethyl 3-hydroxy-2-<(3R,4R)-2-oxo-3-(phenoxyacetylamino)-4-(p-tolylsulfonylthio)-1-azetidinyl>-2-butenoate
• 英文别名: diphenylmethyl 2-[(3R,4R)-4-(p-toluenesulfonylthio)-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-3-hydroxy-2-butenoate；benzhydryl (E)-3-hydroxy-2-[(2R,3R)-2-(4-methylphenyl)sulfonylsulfanyl-4-oxo-3-[(2-phenoxyacetyl)amino]azetidin-1-yl]but-2-enoate
• CAS: 57561-96-3
• 化学式: C₃₅H₃₂N₂O₈S₂
• 分子量: 672.78
• InChiKey: JYBFYDOVDDHVMZ-MLLIXMJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  47
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  173
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  diphenylmethyl 3-hydroxy-2-<(3R,4R)-2-oxo-3-(phenoxyacetylamino)-4-(p-tolylsulfonylthio)-1-azetidinyl>-2-butenoate 在 copper(l) iodide 、 焦硫酰氟 、 TEA 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 Diphenylmethyl (7S,6R)-7-(phenoxyacetamido)-3-tert-butyl-3-cephem-4-carboxylate
  参考文献：
  名称：

  A Novel Approach to Cephalosporins From Allenylazetidinones: A New Cyclization Strategy via Tandem Cuprate Addition-Sulfenylation

  摘要：

  An efficient approach to the synthesis of 3-substituted cephems bearing carbon-based substituents of choice at the C(3) position from inexpensive penicillins is described. The strategy involves the synthesis of an allenylazetidinone from penicillin sulfoxide followed by the addition of an organocuprate at low temperature. Organocuprates undergo 1,4-conjugate addition at the central allenic carbon of the allenylazetidinone to form a carbon-carbon bond which is followed by ring closure via an intramolecular sulfenylation reaction. The chemistry has been applied to the synthesis of a variety of 3-substituted cephems bearing substituents such as alkyl, cycloalkyl, aryl, alkenyl, and allyl. Precursors to the synthesis of important antibiotics, i.e., Cefadroxil, Cefixime, and Cefzil, are also available from this novel approach. The methodology is not limited to carbon-based 3-substituted cephems, but provides access to some 3-norcephalosporins as well.

  DOI：

  10.1021/jo00096a045
• 作为产物：
  描述：

  diphenylmethyl 2-[(3R,4R)-4-(p-toluenesulfonylthio)-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-3-methyl-3-butenoate 在 sodium periodate 、 四氧化锇 作用下， 以 水 、 丙酮 、 叔丁醇 为溶剂， 反应 6.0h， 以97.6%的产率得到diphenylmethyl 3-hydroxy-2-<(3R,4R)-2-oxo-3-(phenoxyacetylamino)-4-(p-tolylsulfonylthio)-1-azetidinyl>-2-butenoate
  参考文献：
  名称：

  A Non Ozone Approach to Enol Azetidinones: Synthetic Precursors to β-Lactam Antibiotics

  摘要：

  烯醇取代的氮杂环丁酮（2-[(3R, 4R)- 4-(2-苯并噻唑基二硫)-2-氧代-3-(苯氧乙酰氨基)-1-氮杂环丁基]-3-羟基-2-丁烯酸二苯甲酯及其衍生物）是合成多种头孢菌素的重要中间体。我们开发了一种四氧化锇/高碘酸钠氧化系统组合，可以高产率制备这些中间体。该方法是臭氧分解法的替代方法。

  DOI：

  10.1055/s-1993-25850

文献信息

• Processes for making cephems from allenylazetidinone derivatives
  申请人：Bristol-Myers Squibb Company

  公开号：US05162524A1

  公开（公告）日：1992-11-10

  This invention relates to a novel process for making a cephem of formula II from a 2-(3-amino-2-oxo-azetidin-1-yl)-2,3-butadienoate intermediate of formula I using an organo-copper reagent. In another aspect, this invention is concerned with said intermediate. ##STR1## In the compounds of Scheme (A), R.sup.1 is a conventional amino protecting group or an acyl group; R.sup.2 is an aromatic heterocyclic or aryl group; R.sup.3 is a conventional carboxy protecting group or --CO.sub.2 R.sup.3 taken together forms a physiologically hydrolyzable ester; and R.sup.4 is a group selected from the group consisting of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, cyclic C.sub.3-6 alkyl, and aryl; and n is 0 or 2. This invention also relates to an intermediate represented by formula ##STR2## in which R.sup.1, R.sup.2, R.sup.3 and n are as defined above.

  这项发明涉及一种从式I的2-(3-氨基-2-氧代氮杂环丙氧基)-2,3-丁二烯酸酯中使用有机铜试剂制备式II头孢菌素的新工艺。在另一个方面，这项发明涉及所述的中间体。在方案(A)的化合物中，R^1是传统的氨基保护基或酰基；R^2是芳香杂环或芳基；R^3是传统的羧基保护基或--CO_2R^3，两者结合形成生理可水解的酯；R^4是选自C_1-6烷基、C_2-6烯基、C_2-6炔基、环状C_3-6烷基和芳基的基团；n为0或2。这项发明还涉及一种由式所表示的中间体 R^1、R^2、R^3和n如上定义。
• US5162521A
  申请人：——

  公开号：US5162521A

  公开（公告）日：1992-11-10
• US5162524A
  申请人：——

  公开号：US5162524A

  公开（公告）日：1992-11-10
• US5266691A
  申请人：——

  公开号：US5266691A

  公开（公告）日：1993-11-30