头孢菌素 C | 61-24-5

• 物质功能分类: 原料药 - 抗生素类药物 - 头孢菌素类药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 头孢菌素 C
• 中文别名: 头孢菌素C(7-ACA)；头孢菌素C
• 英文名称: cephalosporin C
• 英文别名: cephalosporin；(6R,7R)-3-(acetyloxymethyl)-7-[[(5R)-5-amino-5-carboxypentanoyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 61-24-5
• 化学式: C₁₆H₂₁N₃O₈S
• 分子量: 415.424
• InChiKey: HOKIDJSKDBPKTQ-GLXFQSAKSA-N

物化性质

• 沸点：
  814.7±65.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.4
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  202
• 氢给体数：
  4
• 氢受体数：
  10

ADMET

毒理性

• 副作用

皮肤致敏剂 - 一种可以诱导皮肤产生过敏反应的制剂。

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

制备方法与用途

性质

头孢菌素C（简称CPC）是由顶头孢霉(Acremonium chrysogenum)产生的β-内酰胺类抗生素。其结构特点是用二氢噻嗪环代替了青霉素中的噻唑环与β-内酰胺环相连，这种结构差异使其具有更强的稳定性，不易被青霉素酶破坏，能够有效杀死许多青霉素耐药菌。

化学性质

头孢菌素C钠盐二水合物为单斜晶体。它溶于水而不溶于乙醇和乙醚。在pH值2.5至8的水中溶液中是稳定的。

用途

头孢菌素C对金黄色葡萄球菌、伤寒杆菌及大肠杆菌具有活性。但由于其抗菌活力较低，临床应用并不广泛。不过，通过改造可以制备出高效衍生物，目前它主要作为合成7-氨基头孢霉烷酸（7-ACA）的中间体。

生产方法

头孢菌素C通过发酵法生产。

反应信息

• 作为反应物：
  描述：

  头孢菌素 C 在 phosphate buffer 、 enzyme derivative DAO 、 enzyme derivative GA 、 PGA E_. coli A 作用下， 反应 5.0h， 生成 头孢唑啉
  参考文献：
  名称：

  One-Pot Chemoenzymatic Synthesis of 3‘-Functionalized Cephalosporines (Cefazolin) by Three Consecutive Biotransformations in Fully Aqueous Medium

  摘要：

  We illustrate a new chemoenzymatic synthesis of cefazolin from cephalosporin C, involving three consecutive biotransformations in full aqueous medium. This one-pot three-step synthesis includes the D-amino acid oxidase catalyzed oxidative deamination of the cephalosporin C side chain, hydrolysis of the resulting glutaryl derivative catalyzed by glutaryl acylase, and the final penicillin G acylase (PGA)-catalyzed acylation of 7-aminocephalosporanic acid (1, 7-ACA). The product, 7-[(1H-tetrazol-1-yl)acetamido]-3-(acetoxymethyl)-Delta(3)-cephem-4-carboxylic acid (5), was used as an intermediate for cefazolin synthesis by 3'-acetoxy group displacement with 2-mercapto-5-methyl-1,3,4-thiadiazole. Very high yields have been achieved with all the enzymatic reactions performed; high product concentrations were obtained in short reaction times. This synthetic approach presents several advantages when compared with the conventional chemical processes. The use of the toxic reagents and chlorinated solvents is avoided, while the substrate specificity and chemoselectivity of the enzymes makes reactive group protection and intermediate purification unnecessary. The enzymatic deacylation of cephalosporin C was performed by the simultaneous use of D-amino acid oxidase and glutaryl acylase. The substrate specificity of PGA allowed the acylation of 7-ACA (1) to be performed without purification from the glutaric acid produced during the enzymatic deacylation. These results were achieved by optimization and correct assembly of the different biotransformations involved. Special attention has been applied to the kinetically controlled acylation reaction. High yields were obtained through a careful selection of the enzyme catalyst, experimental conditions, and synthetic strategy.

  DOI：

  10.1021/jo971166u
• 作为产物：
  描述：

  cephalosporin C zinc salt 生成 头孢菌素 C
  参考文献：
  名称：

  GALIMULINA, K. R.;EGOROV, V. L., MOLEKUL. SORBTSIYA BIOL. AKTIV. VESHCHESTV: TEZ. DOKL. K ZONAL. KONF.,

  摘要：

  DOI：

文献信息

• DERIVATIVES OF RELEBACTAM AND USES THEREOF
  申请人：ARIXA PHARMACEUTICALS, INC.

  公开号：US20200102307A1

  公开（公告）日：2020-04-02

  Derivatives of relebactam, therapeutic methods of using the derivatives of relebactam, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The derivatives of relebactam are suitable for oral administration.

  Relebactam的衍生物、使用Relebactam的衍生物的治疗方法，特别是与β-内酰胺类抗生素结合使用以及其制药组合物已被披露。Relebactam的衍生物适合口服给药。
• [EN] PROGRAMMABLE POLYMERIC DRUGS<br/>[FR] MÉDICAMENTS POLYMÈRES PROGRAMMABLES
  申请人：SONY CORP

  公开号：WO2020210689A1

  公开（公告）日：2020-10-15

  Compounds useful as biologically active compounds are disclosed. The compounds have the following structure (I): or a stereoisomer, tautomer or salt thereof, wherein R1, R2, R3, R4, R5, L, L1, L2, M and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

  披露了作为生物活性化合物有用的化合物。这些化合物具有以下结构（I）：或其立体异构体、互变异构体或盐，其中R1、R2、R3、R4、R5、L、L1、L2、M和n如本文所定义。还提供了与这些化合物的制备和使用相关的方法。
• FUNCTIONALLY-MODIFIED OLIGONUCLEOTIDES AND SUBUNITS THEREOF
  申请人：Sarepta Therapeutics, Inc.

  公开号：US20140330006A1

  公开（公告）日：2014-11-06

  Functionally-modified oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3′ and/or 5′-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

  提供了包含修改的亚单位间连接和/或修改的3'和/或5'-末端基团的功能修饰寡核苷酸类似物。所公开的化合物对于治疗需要抑制蛋白质表达或纠正异常mRNA剪接产物以产生有益治疗效果的疾病是有用的。
• Beta-lactamase inhibitors and uses thereof
  申请人：ARIXA PHARMACEUTICALS, INC.

  公开号：US10085999B1

  公开（公告）日：2018-10-02

  β-Lactamase inhibiting compounds, therapeutic methods of using the β-lactamase inhibiting compounds, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The β-lactamase inhibiting compounds are suitable for oral administration.

  β-内酰胺酶抑制化合物，使用β-内酰胺酶抑制化合物的治疗方法，特别是与β-内酰胺类抗生素结合以及其制药组合物被披露。这些β-内酰胺酶抑制化合物适合口服给药。
• AZTREONAM DERIVATIVES AND USES THEREOF
  申请人：ARIXA PHARMACEUTICALS, INC.

  公开号：US20190100516A1

  公开（公告）日：2019-04-04

  Disclosed herein are aztreonam derivatives, therapeutic methods of using the aztreonam derivatives, particularly in combination with β-lactamase inhibitors, and pharmaceutical compositions thereof. The aztreonam derivatives can be administered orally to provide orally bioavailable aztreonam.

  本文披露了阿特雷纳姆衍生物，使用阿特雷纳姆衍生物的治疗方法，特别是与β-内酰胺酶抑制剂结合使用的方法，以及它们的药物组成物。这些阿特雷纳姆衍生物可以口服给药，从而提供口服可利用的阿特雷纳姆。