p-nitrobenzyl (7S,6R)-7-(phenoxyacetamido)-3-{[(trifluoromethyl)sulfonyl]oxy}-1-carba-1-dethia-3-cephem-4-carboxylate | 108493-71-6

• 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 (7S,6R)-7-(phenoxyacetamido)-3-{[(trifluoromethyl)sulfonyl]oxy}-1-carba-1-dethia-3-cephem-4-carboxylate
• 英文别名: (4-nitrophenyl)methyl (6R,7S)-8-oxo-7-[(2-phenoxyacetyl)amino]-3-(trifluoromethylsulfonyloxy)-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 108493-71-6
• 化学式: C₂₄H₂₀F₃N₃O₁₀S
• 分子量: 599.498
• InChiKey: BTLCDBSGXDABNN-XLIONFOSSA-N

物化性质

• 沸点：
  796.6±60.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  183
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  p-nitrobenzyl (7S,6R)-7-(phenoxyacetamido)-3-{[(trifluoromethyl)sulfonyl]oxy}-1-carba-1-dethia-3-cephem-4-carboxylate 在 palladium diacetate N-甲基吗啉 、 盐酸 、 chloro-dimethoxy-triazine 、 三正丁基氢锡 、 碳酸氢钠 、 四正丁基硫酸铵 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 乙醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.0h， 生成 7β-<2-(2-aminothiazol-4-yl)-2(Z)-(methoxyimino)acetamido>-3-(isopropylsulfonyl)-1-carba-1-dethia-3-cephem-4-carboxylic acid
  参考文献：
  名称：

  3-磺酰基-1-氨基-1-去硫脑。

  摘要：

  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=

  DOI：

  10.1021/jm00131a005
• 作为产物：
  描述：

  (3R-trans)-3-phenoxyacetylamino-4-phenylsulfonyl-2-azetidinone 在 吡啶 、 盐酸 、 二甲基硫 、 4 A molecular sieve 、 四氯化锡 、 臭氧 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 20.0h， 生成 p-nitrobenzyl (7S,6R)-7-(phenoxyacetamido)-3-{[(trifluoromethyl)sulfonyl]oxy}-1-carba-1-dethia-3-cephem-4-carboxylate
  参考文献：
  名称：

  Halide-Terminated N-Acyliminium Ion−Alkyne Cyclizations:  A New Construction of Carbacephem Antibiotics

  摘要：

  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.

  DOI：

  10.1021/jo971433w

文献信息

• 3-Quaternary ammonium 1-carba-1-dethiacephems
  作者：Gwendolyn K. Cook、John H. McDonald、William Alborn、Donald B. Boyd、Judy A. Eudaly、Joseph M. Indelicato、Rod Johnson、Jeffrey S. Kasher、Carol E. Pasini

  DOI：10.1021/jm00131a006

  日期：1989.11

  with or without warning to 50 degrees C. Bases nucleophilic enough to displace the triflate include a variety of substituted pyridines and N-methylimidazole. Deprotection then produced a very active series of 1-[7 beta-[(2-amino- 4-thiazolyl)(methoxyimino)acetyl]amino]-2-carboxy-8-oxo- 1-azabicyclo[4.2.0]oct-2-en-3-yl] quaternary ammonium hydroxide inner salts. These compounds were extremely potent antibacterials

  描述了一系列结构独特的1-carba-1-dethiacephems。1-carba-1-dethiacephem核的结构稳定性对于制备该系列的3-季铵碳萘啶是至关重要的。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-carba-1-dethia-3-cephem-4-羧酸酯既用作季铵化底物，又用作前体衍生物，例如烯丙基7β-[[[2- [烯丙基氧基]羰基]氨基-4-噻唑基] [（甲氧基亚氨基）乙酰基]氨基] -3-[（（三氟甲基）磺酰基]氧] -1-碳-1-1-硫醇-3 -cephem-4-羧酸盐。这些烯醇三氟甲磺酸酯的季铵化反应可通过溶解在含有碱的乙腈中或通过溶解在碱中来实现，无论是否警告到50摄氏度。足以取代三氟甲磺酸酯的亲核碱基包括各种取代的吡啶和N-甲基咪唑。然后脱保护产生了一系列非常活跃的1- [7β-[（2-氨基-4-噻唑基）（甲氧基亚氨基）乙酰基]氨基]
• Synthesis and in vitro antibacterial activities of 3-thiazol 4 yl-carba-l-dethiacephalosporins.
  作者：WILLIAM J. HORNBACK、JOHN E. MUNROE、FRED T. COUNTER

  DOI：10.7164/antibiotics.47.1052

  日期：——

  The synthesis and microbiological evaluation of a new series of 3-thiazol-4-yl-carba-1-dethiacephalosporins is described. Structure activity relationship was achieved by changing substitution at the 2-position of the thiazole moiety. The result was a marked variance of microbiological activity in the C7 side-chain derivatives. ATMO derivatives possess potent activity against both Gram-positive and Gram-negative bacteria. For example, MICs (μg/ml) of LY215226 against representative organisms are as follows: S. aureus 0.25, S. pneumoniae 0.008, H. influenzae 0.008, E. coli 0.25, K. pneumoniae 0.008, E. cloacae 0.5, S. typhi 0.25, and M. morganii 0.25.

  描述了一系列新的3-噻唑-4-基-卡巴-1-去硫头孢菌素的合成和微生物学评估。通过改变噻唑部分的2位取代来实现结构-活性关系。结果表明，C7侧链衍生物在微生物活性上存在明显差异。ATMO衍生物对革兰阳性和革兰阴性细菌均具有强效活性。例如，LY215226对典型微生物的最低抑菌浓度（MIC，μg/ml）如下：金黄色葡萄球菌0.25，肺炎链球菌0.008，流感嗜血杆菌0.008，大肠杆菌0.25，肺炎克雷伯菌0.008，克隆氏菌0.5，伤寒沙门氏菌0.25，以及摩根氏菌0.25。
• 3-Trifluoromethylcarbacephems: Synthesis of broad spectrum antibacterial compounds
  作者：G.K. Cook、W.J. Hornback、J.H. McDonald、J.E. Munroe、N.J. Snyder

  DOI：10.1016/s0960-894x(98)00204-2

  日期：1998.5

  The enhanced stability of the carbacephem nucleus over the corresponding cephalosporin nucleus has allowed the synthesis of 7-arylglycyl-3-trifluoromethyl-carbacephems. These unique carbacephems possess broad spectrum activity and high stability to both plasmid and chromosomally mediated beta-lactamases. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Palladium-catalyzed chemistry of .beta.-lactam vinyl triflates: coupling with organostannanes and alkoxycarbonylation
  作者：Gwendolyn K. Cook、William J. Hornback、Chris L. Jordan、John H. McDonald、John E. Munroe

  DOI：10.1021/jo00285a037

  日期：1989.11
• Comparative reactivity of 1-carba-1-dethiacephalosporins with cephalosporins
  作者：Larry C. Blaszczak、Raymond F. Brown、Gwendolyn K. Cook、William J. Hornback、Joseph M. Indelicato、Chris L. Jordan、Alan S. Katner、Michael D. Kinnick、John H. McDonald

  DOI：10.1021/jm00168a019

  日期：1990.6

  Nine matched pairs of cephalosporins and their 1-carba-1-dethiacephalosporin analogues have been compared with regard to microbiological activity, beta-lactam carbonyl infrared absorption, and aqueous stability. In general the microbiological activity of the pairs of compounds were very similar across a broad range of bacteria. The infrared absorption bands for the beta-lactam carbonyls of the pairs indicated a general trend for the 1-carba-1-dethiacephalosporins to absorb at lower frequencies than the corresponding cephalosporins. All of the 1-carba-1-dethiacephalosporins did however present a striking stability enhancement over their cephalosporin counterparts at pH = 10 or 11 in water. This marked contrast of MIC similarity with the observed differences in chemical reactivity clearly demonstrates hydroxide ion catalyzed hydrolysis is not a good model for transpeptidase activity unless the compounds comprise a limited domain of structural type.