Diphenylmethyl 2-<(3R,4R)-<(p-toluenesulfonyl)thio>-3-(phenoxyacetamido)-2-oxoazetidin-1-yl>-3-<(fluorosulfonyl)oxy>-2-butenoate

• 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: Diphenylmethyl 2-<(3R,4R)-<(p-toluenesulfonyl)thio>-3-(phenoxyacetamido)-2-oxoazetidin-1-yl>-3-<(fluorosulfonyl)oxy>-2-butenoate
• 英文别名: Diphenylmethyl 2-[(3R,4R)-4-(p-toluenesulfonylthio)-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-3-fluorosulfonyloxy-2-butenoate；benzhydryl (E)-3-fluorosulfonyloxy-2-[(2R,3R)-2-(4-methylphenyl)sulfonylsulfanyl-4-oxo-3-[(2-phenoxyacetyl)amino]azetidin-1-yl]but-2-enoate
• 化学式: C₃₅H₃₁FN₂O₁₀S₃
• 分子量: 754.835
• InChiKey: GOZONMGLZMEDIM-MLLIXMJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  51
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  205
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  Diphenylmethyl 2-<(3R,4R)-<(p-toluenesulfonyl)thio>-3-(phenoxyacetamido)-2-oxoazetidin-1-yl>-3-<(fluorosulfonyl)oxy>-2-butenoate 在 TEA 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以90%的产率得到Diphenylmethyl 2-<(3R,4R)-4-<(p-toluenesulfonyl)thio>-3-(phenoxyacetamido)-2-oxoazetidin-1-yl>-2,3-butadienoate
  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 3-hydroxy-2-<(3R,4R)-2-oxo-3-(phenoxyacetylamino)-4-(p-tolylsulfonylthio)-1-azetidinyl>-2-butenoate 在 焦硫酰氟 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以86.5%的产率得到Diphenylmethyl 2-<(3R,4R)-<(p-toluenesulfonyl)thio>-3-(phenoxyacetamido)-2-oxoazetidin-1-yl>-3-<(fluorosulfonyl)oxy>-2-butenoate
  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

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
• A Novel Approach to Cephalosporins From Allenylazetidinones: A New Cyclization Strategy via Tandem Cuprate Addition-Sulfenylation
  作者：Joydeep Kant、Jeanine A. Roth、Carl E. Fuller、Donald G. Walker、Daniel A. Benigni、Vittorio Farina

  DOI：10.1021/jo00096a045

  日期：1994.8

  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.