p-nitrobenzyl 7β-[(phenoxyacetyl)amino]-3-hydroxy-1-carba-1-dethia-3-cephem-4-carboxylate | 119892-46-5

• 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: p-nitrobenzyl 7β-[(phenoxyacetyl)amino]-3-hydroxy-1-carba-1-dethia-3-cephem-4-carboxylate
• 英文别名: (4-nitrophenyl)methyl (6R,7S)-3-hydroxy-8-oxo-7-[(2-phenoxyacetyl)amino]-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 119892-46-5
• 化学式: C₂₃H₂₁N₃O₈
• 分子量: 467.435
• InChiKey: FTQDMGMSOMVZHO-XLIONFOSSA-N

物化性质

• 沸点：
  780.6±60.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  151
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  p-nitrobenzyl 7β-[(phenoxyacetyl)amino]-3-hydroxy-1-carba-1-dethia-3-cephem-4-carboxylate 在 N,N-二甲基丁胺 盐酸 、 (PhO)3P*Cl₂ 、 TEA 、 氯甲酸异丁酯 作用下， 以 吡啶 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 氯碳头孢
  参考文献：
  名称：

  An enantioselective synthesis of loracarbef (LY163892/KT3777)

  摘要：

  DOI：

  10.1016/s0040-4039(01)80388-9
• 作为产物：
  描述：

  cis-β,4-dioxo-3-[(phenoxyacetyl)amino]-2-azetidinepentanoic acid, (4-nitrophenyl)methyl ester 在 Rh₂(O₂CC₇H₁₅)4 p-dodecyl-SO₂N₃ 、 TEA 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 p-nitrobenzyl 7β-[(phenoxyacetyl)amino]-3-hydroxy-1-carba-1-dethia-3-cephem-4-carboxylate
  参考文献：
  名称：

  An enantioselective synthesis of loracarbef (LY163892/KT3777)

  摘要：

  DOI：

  10.1016/s0040-4039(01)80388-9

文献信息

• 3-Sulfonyl-1-carba-1-dethiacephems
  作者：Thomas A. Crowell、Basil D. Halliday、John H. McDonald、Joseph M. Indelicato、Carol E. Pasini、Ernie C. Y. Wu

  DOI：10.1021/jm00131a005

  日期：1989.11

  The stability of the 1-carba-1-dethiacephalosporin framework has allowed the synthesis of a range of 3-sulfonyl-1-carba-1-dethiacephems unavailable for a variety of reasons in the cephem arena. The known p-nitrobenzyl 7 beta-(phenoxyacetamido)-3-[[(trifluoromethyl)sulfonyl]oxy]-1-carba -1- dethia-3-cephem-4-carboxylate served as a precursor to this series of compounds. Displacement of the enol triflate

  1-carba-1-dethiacephalosporin框架的稳定性已允许在头孢烯领域合成因各种原因而无法使用的一系列3-磺酰基-1-carba-1-dethiacephems。已知的对硝基苄基7β-（苯氧基乙酰胺基）-3-[[（（三氟甲基）磺酰基]氧基] -1-咔基-1-dethia-3-cephem-4-羧酸盐用作该系列化合物的前体。在乙腈或DMF中用各种亚磺酸盐置换烯醇三氟甲磺酸酯，并对中间体进行脱保护，得到7β-[（2-氨基-4-噻唑基）（甲氧基亚氨基）乙酰基]氨基]-3- [烷基（芳基）磺酰基]- 1-carba-1-dethia-3-cephem-4-羧酸。3-磺酰基-1-carba-1-dethiacephems对革兰氏阳性菌和革兰氏阴性菌均显示有效的活性。以下是3-环丙基砜的MIC（微克/ mL）：金黄色葡萄球菌= 4，化脓链球菌= 1，流感嗜血杆菌= 0.25，大肠杆菌=
• Synthesis of carbacephem antibiotics: synthesis via dieckmann reaction using phenyl esters to direct the regioselectivity of the cyclization
  作者：Bill G. Jackson、John P. Gardner、Perry C. Heath

  DOI：10.1016/s0040-4039(00)97052-7

  日期：1990.1

  β-Ketoesters useful for elaboration to carbacephems were synthesized from a variety of enantiomerically pure diesters. Use of phenyl esters to direct the regioselectivity was demonstrated.

  由多种对映体纯的二酯合成了可用于精制羧甲基的β-酮酸酯。证明了使用苯基酯指导区域选择性。
• Halide-Terminated <i>N</i>-Acyliminium Ion−Alkyne Cyclizations:  A New Construction of Carbacephem Antibiotics
  作者：Eric Metais、Larry E. Overman、Maria Inés Rodriguez、Brian A. Stearns

  DOI：10.1021/jo971433w

  日期：1997.12.1

  A series of 4-(3-alkynyl)azetidinones 13 was prepared from 4-(phenylsulfonyl)azetidine-2-one (9) and isopropyl glyoxylate hydrate. The 3-pentynyl (13a) and 4-phenyl-3-butynyl (13b) azetidinone acetates underwent 6-exo cyclization when treated with 3 equiv of SnCl4 at 0 degrees C to provide 3-(1-chloroalkylidene)carbacephems 15a (65%) and 15b (33%) respectively. In contrast, the 5-butynyl (13d) and 4-(trimethylsilyl)-3-butynyl (13c) azetidinone acetates under ent 7-endo cyclization under similar conditions to give 1-azabicyclo[5.2.0]nonenes 14a (11%) and 14b (71%), respectively. Beginning with penicillin degradation product 18, the more elaborate 3-pentynyl azetidinone cyclization substrate 27 was prepared in seven steps. Exposure to 27 to 3 equiv of SnCl4 in CH2Cl2 at 0 degrees C for 6 h, followed by allowing the reaction mixture to warm to rt, provided the desired 3-(1-chloroethylidene)carbacephem 28 in 60% yield and high (>99%) enantiometric purity. Cleavage of the chloroethylidene group of 28 with ozone gave 3-hydroxy carbacephem 29 in 77% yield. Since this intermediate has been converted in three steps to loracarbef (3), a new formal total synthesis of this carbacephem antiboitic was concluded.
• Kinetic Differences in the Chlorination of Cephalosporin versus Carbacephalosporin Enols: Evidence of Sulfur Neighboring Group Participation
  作者：John E. Burks、Erik C. Chelius、Ross A. Johnson

  DOI：10.1021/jo00098a034

  日期：1994.9

  Intermediates in the chlorination of carbacephalosporin and cephalosporin enols with chlorotriph-enoxyphosphonium chloride, (PHO)(3)P+Cl Cl-, have been characterized at low temperatures by NMR. P-31 NMR has been used to determine the rate constants and Arrhenius activation energies for the chlorination of the cephalosporin enol 1b and the carbacephalosporin enol 1c. The results show a 3.7 kcal/mol lower activation energy for the chlorination of the cephalosporin enol. Semiempirical and ab initio calculations have been employed to evaluate chloride attack and phosphate departure for model cephalosporin and carbacephalosporin enols. The experimental and computational results are consistent with a chlorination mechanism that involves rapid, reversible chloride addition to an intermediate enol phosphonium species followed by rate-limiting phosphate departure. The lower activation energy for phosphate departure in the cephalosporin case is attributed to sulfur neighboring group participation.
• Use of an iodonium ylide in the synthesis of p-nitrobenzyl (6R, 7S) 3-hydroxy-8-oxo-7-phenoxyacetamino-1-azabicyclo[4.2.0]octa-2-ene-2-carboxylate
  作者：Radhe K. Vaid、Thomas E. Hopkins

  DOI：10.1016/s0040-4039(97)01669-9

  日期：1997.10

  p-Nitrobenzyl (6R,7S)-3-hydroxy-8-oxo-7-phenoxyacetamido-1-azabicyclo [4.2.0]octa-2-ene-2-carboxyate (6) was synthesized utilizing rhodium(II)- or acid-catalyzed cyclization of iodonium ylide (5). The iodonium ylide (5) was easily prepared from the corresponding beta-keto ester (4) and[(diacetoxy)iodo]benzene in good yield. (C) 1997 Elsevier Science Ltd.