4-硝基苄基(6S,7S)-7-氨基-3-甲基-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸酯 | 29124-83-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-硝基苄基(6S,7S)-7-氨基-3-甲基-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸酯
• 英文名称: p-nitrobenzyl 7β-amino-desacetoxycephalosporanate
• 英文别名: p-NB ester of 7-aminodeacetoxycephalosporanic acid；p-nitrobenzyl ester of 7-aminodeacetoxycephalosporanic acid；p-nitrobenzyl 7-amino-3-methyl-3-cephem-4-carboxylate；p-Nitrobenzyl-7-amino-3-methyl-3-cephem-4-carboxylat；(6R)-7t-amino-3-methyl-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 4-nitro-benzyl ester；(4-nitrophenyl)methyl (6R,7R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 29124-83-2
• 化学式: C₁₅H₁₅N₃O₅S
• 分子量: 349.367
• InChiKey: ABTUPEBOWRKQLD-BXUZGUMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  144
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-硝基苄基(6S,7S)-7-氨基-3-甲基-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸酯 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 tert-butyl (2S)-4-methyl-2-[[(6R,7R)-3-methyl-7-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbonyl]amino]pentanoate
  参考文献：
  名称：

  Pitlik; Bagossi; Jekoe, Pharmazie, 1996, vol. 51, # 10, p. 700 - 704

  摘要：

  DOI：
• 作为产物：
  描述：

  1ξ-oxo-6β-(2-phenyl-acetylamino)-1λ⁴-penicillanic acid 4-nitro-benzyl ester 在 pyridinium trichloroethyl phosphate 作用下， 以 甲苯 为溶剂， 生成 4-硝基苄基(6S,7S)-7-氨基-3-甲基-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸酯
  参考文献：
  名称：

  Conversion of acylamidopenicillins to phosphoramidopenicillins, and removal of their phosphoryl side chain.

  摘要：

  用五氯化磷、甲醇、碳酸氢钠或二甲基苯胺依次处理苄基青霉烷酸酯（1）或其硫醚（7），可得到 6-（二甲基磷酰氨基）青霉素（5）或其硫醚（8）。6-（二甲基磷酰氨基）青霉素硫醚（8）经热重排后生成相应的去乙酰氧基头孢菌素（10）。用 85% 的磷酸或多磷酸去除 7-（二甲基磷酰氨基）去乙酰氧基头孢菌素（10）的二甲基磷酰基，可使 6-（二甲基磷酰氨基）青霉素（5）及其硫醚（8）中的 β-内酰胺环降解。青霉素和去乙酰氧基头孢菌素的二甲基磷酰也可通过光气和吡啶去除，分别得到 6-异氰酸青霉素（16）和 7-异氰酸去乙酰氧基头孢菌素（15）。

  DOI：

  10.1248/cpb.24.3058

文献信息

• Orally absorbable cephalosporin antibiotics. 3. Preparation of biologically active R-isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid
  作者：Stjepan Kukolja、Janice L. Pfeil、Susan E. Draheim、John L. Ott

  DOI：10.1021/jm00150a024

  日期：1985.12

  were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7. After removal of the Boc and p-NB groups, the R isomer of 7-(3-benzo

  将（RS）-3-苯并噻吩基甘氨酸的甲基和异丙基酯用（+）-和（-）-酒石酸在乙腈中拆分，得到相应的R和S盐。R盐4水解为（R）-3-苯并噻吩基甘氨酸（5）。5中的氨基被Boc功能保护，被保护的R氨基酸6与7-ADCA的p-NB酯偶联，得到双保护的头孢菌素7。除去Boc和p-NB基团后，R异构体获得了7-（3-苯并噻吩基糖基氨基）脱乙酰氧基头孢菌酸（1）。通过制备色谱将差向性头孢菌素7的p-NB酯分离为R和S异构体。除去保护基后，分离出S差向异构体。报道了R和S差向异构体与头孢菌素1的RS混合物的抗菌活性的比较。
• X=Y-ZH systems as potential 1,3-Dipoles. Part 46.1 cascade 1,3-dipolar cycloaddition reactions of cephalosporin imines
  作者：Ronald Grigg、Peter McMeekin、Visuvanathar Sridharan

  DOI：10.1016/0040-4020(95)00847-2

  日期：1995.11

  Proton sponge effects in ortho-OMe and -NMe2 arylidene imines of 7-aminocephalosporins promote thermal (toluene. 110 °C) 1,2-prototropy to give mixtures of E,E- and E,Z-azomethine ylides which undergo diastereofacially specific (α-face) cycloaddilion to N-phenylmaleimide to give mixtures of mainly endo-cycloadducts in excellent yield.

  7-氨基头孢菌素的邻-OMe和-NMe 2亚芳基亚胺中的质子海绵效应促进热（甲苯。110°C）1,2-亲质性，产生E，E-和E，Z-偶氮甲亚胺混合物，这些混合物经历非对映体特异性（α-面）环加成至N-苯基马来酰亚胺，以优异的产率得到主要为内环加合物的混合物。
• Orally absorbable cephalosporin antibiotics. 2. Structure-activity studies of bicyclic glycine derivatives of 7-aminodeacetoxycephalosporanic acid
  作者：Stjepan Kukolja、Susan E. Draheim、Bernard J. Graves、David C. Hunden、Janice L. Pfeil、Robin D. G. Cooper、John L. Ott、Fred T. Counter

  DOI：10.1021/jm00150a023

  日期：1985.12

  Three positional analogues (4-, 5-, and 7-) of benzothienylglycine and (N-acetylindolinyl)-5-glycine were prepared and coupled to 7-aminodeacetoxycephalosporanic acid (7-ADCA) to give the cephalosporins 17a-c. In addition two isomeric (2,3-b and 3,2-b) thienothiopheneglycines were synthesized and coupled to 7-ADCA to yield cephalosporins 30d and 30e. In vitro testing of these new cephalosporins indicates good activity against Gram-positive bacteria. Against Streptococcus pneumoniae infections compound 25 displayed better mouse protection (both orally and subcutaneously) than cephalexin.
• Orally absorbable cephalosporin antibiotics. 1. Structure-activity relationships of benzothienyl- and naphthylglycine derivatives of 7-aminodeacetoxycephalosporanic acid
  作者：Stjepan Kukolja、Susan E. Draheim、Janice L. Pfeil、Robin D. G. Cooper、Bernard J. Graves、Richard E. Holmes、David A. Neel、George W. Huffman、J. Alan Webber

  DOI：10.1021/jm00150a022

  日期：1985.12

  A structure-activity relationship study of a number of orally absorbed cephalosporins together with their syntheses is described. These new cephalosporins are benzothienyl- and naphthylglycine derivatives of 7-aminodeacetoxycephalosporanic acid. Several different synthetic methods for the glycine side chains, their protection, and the final acylations are reported. Several of these analogues were more active than cephalexin both in vitro and in vivo against commonly encountered Gram-positive bacteria. (R)-7-(3-Benzothienylglycylamido)-3-methyl-3-cephem-4-carboxylic acid (1R) has emerged as a potent antibacterial agent and is currently undergoing preclinical evaluation.
• Azetidinone antibiotics. XIV. Removal of a phthaloyl protective group from acid and base sensitive compounds
  作者：Stjepan Kukolja、Steven R. Lammert

  DOI：10.1021/ja00852a044

  日期：1975.9