tert-butyl (6R,7R)-3-(acetoxymethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | 53638-83-8

• 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: tert-butyl (6R,7R)-3-(acetoxymethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• 英文别名: Cephaloram-tert.butylester；(6R,7R)-tert-butyl 3-(acetoxymethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate；(6R)-3-acetoxymethyl-8-oxo-7t-(2-phenyl-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid tert-butyl ester；7β-(2-phenyl-acetylamino)-cephalosporanic acid tert-butyl ester；7-(phenylacetamido)cephalosporanic acid t-butyl ester；tert-butyl (6R,7R)-3-(acetyloxymethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 53638-83-8
• 化学式: C₂₂H₂₆N₂O₆S
• 分子量: 446.524
• InChiKey: SWKQYAZPNHEONW-YLJYHZDGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (6R,7R)-3-(acetoxymethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 在 Candida antarctica lipase B 作用下， 以 四氢呋喃 、 正己烷 、 仲丁醇 为溶剂， 反应 96.0h， 以97%的产率得到tert-butyl (7R,7aR)-3-(hydroxymethyl)-6-oxo-7-[(2-phenylacetyl)amino]-7,7a-dihydro-2H,6H-azeto[2,1-b][1,3]thiazine-4-carboxylate
  参考文献：
  名称：

  Enzymatic Deprotection of the Cephalosporin 3′-Acetoxy Group Using Candida antarctica Lipase B

  摘要：

  Cephalosporins remain one of the most important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3'-hydroxymethyl position. While 3'-acetoxymethyl-substituted cephalosporins are readily available, deacetylation to access the free 3'-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or tert-butyl esters and on the corresponding sulfoxide and sulfone of the tert-butyl ester.

  DOI：

  10.1021/jo902406b
• 作为产物：
  描述：

  7-氨基头孢烷酸 在 对甲苯磺酸 作用下， 反应 8.25h， 生成 tert-butyl (6R,7R)-3-(acetoxymethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  头孢烯-吡嗪酸缀合物：规避结核分枝杆菌的耐药性

  摘要：

  合成了头孢烯-吡嗪酸 (POA)缀合物作为治疗耐药结核病 (TB) 的新型药物。我们的策略规避了pncA相关耐药突变，该突变威胁着一线抗结核吡嗪酰胺 (PZA) 的继续使用，并且还表现出针对其他耐药菌株和模型的有希望的活性，通过双重治疗方式的联合作用实现了协同药物作用。

  DOI：

  10.1002/chem.202200995

文献信息

• 7-.alpha. substituted imino 7-.beta. substituted thio cephalosporin
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04071682A1

  公开（公告）日：1978-01-31

  An improved, versatile method for producing 7-cephalosporin derivatives having a 7-alkylthio or 7-arylthio group which comprises treating a 7-substituted imino halide, imino ether or iminothio ether of 7-aminocephalosporanic acid, 7-amino-3-desacetoxycephalosporanic acid and the like with a thiolating agent in the presence of a base, to obtain the thio derivative. These products are particularly useful for conversion to 7.alpha.-alkylthio or 7.alpha.-arylthio-7-acylamino intermediates which are converted to lower alkoxy cephalosporin derivatives useful as antibacterial agents.

  一种改进的、多功能的方法，用于制备具有7-烷硫基或7-芳基硫基的7-头孢菌素衍生物，包括将7-取代的亚胺卤化物、亚胺醚或亚胺硫醚与7-氨基头孢菌素酸、7-氨基-3-去乙酰氧头孢菌素酸等在碱的存在下与硫化剂反应，以获得硫衍生物。这些产品特别适用于转化为7.alpha.-烷硫基或7.alpha.-芳基硫基-7-酰氨基中间体，这些中间体可转化为有用的抗菌剂的较低烷氧头孢菌素衍生物。
• Cephalosporins
  申请人：Glaxo Laboratories Limited

  公开号：US03976546A1

  公开（公告）日：1976-08-24

  3-Acyloxymethylceph-3-em-4-carboxylic acids, for example cephalosporin C, are enzymically deacylated to their 3-hydroxymethyl analogues by means of esterases produced by culturing microorganisms or mutants thereof of the class Basidiomycetes, particularly of the genus Rhodosporidium, for example a microorganism of the species Rhodosporidium toruloides.

  例如头孢菌素C等3-酰氧甲基头孢-3-酮-4-羧酸可以通过培养类担子菌类（Basidiomycetes）的微生物或其突变体产生的酯酶，特别是属于红孢酵母属（Rhodosporidium）的微生物，例如红孢酵母属（Rhodosporidium toruloides）的微生物，进行酯化作用，使其脱酰基，形成相应的3-羟甲基类似物。
• 7-N-Amidinocephalosporins
  作者：J. Altman、E. Karoly、N. Maoz

  DOI：10.1021/jm00240a023

  日期：1975.6

  7-Aminocephalosporanic acid tert-butyl ester reacts quantitatively at--20 degrees with iminium chlorides to give amidino derivatives. Removal of the tert-butyl protecting group with trifluoroacetic acid and treatment with 1 equiv of triethylamine yield the corresponding zwitterions. These compounds were less active than their penicillin analogs.
• US4071682A
  申请人：——

  公开号：US4071682A

  公开（公告）日：1978-01-31
• Enzymatic Deprotection of the Cephalosporin 3′-Acetoxy Group Using <i>Candida antarctica</i> Lipase B
  作者：Leslie D. Patterson、Marvin J. Miller

  DOI：10.1021/jo902406b

  日期：2010.2.19

  Cephalosporins remain one of the most important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3'-hydroxymethyl position. While 3'-acetoxymethyl-substituted cephalosporins are readily available, deacetylation to access the free 3'-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or tert-butyl esters and on the corresponding sulfoxide and sulfone of the tert-butyl ester.