氯霉素 1-乙酸酯 | 23214-93-9

• 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: 氯霉素 1-乙酸酯
• 中文别名: 氯霉素1-乙酸酯
• 英文名称: (1R,2R)-2-(2,2-dichloroacetamido)-3-hydroxy-1-(4-nitrophenyl)propyl acetate
• 英文别名: (1R,2R)-2-[(dichloroacetyl)amino]-3-hydroxy-1-(4-nitrophenyl)propyl acetate；chloramphenicol-1-yl acetate；1'-O-acetylchloramphenicol；1-O-acetylchlorampenicol；1-acetylchloramphenicol；(2'R,3'R)-chloramphenicol 1'-acetate；Chloramphenicol 1-acetate；[(1R,2R)-2-[(2,2-dichloroacetyl)amino]-3-hydroxy-1-(4-nitrophenyl)propyl] acetate
• CAS: 23214-93-9
• 化学式: C₁₃H₁₄Cl₂N₂O₆
• 分子量: 365.17
• InChiKey: WEYAPUCXWINQDH-GHMZBOCLSA-N

物化性质

• 熔点：
  >119°C (dec.)
• 沸点：
  569.5±50.0 °C(Predicted)
• 密度：
  1.473±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、乙酸乙酯、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2924299090
• 储存条件：
  -20°C

反应信息

• 作为反应物：
  描述：

  氯霉素 1-乙酸酯 在 高碘酸 、 pyridinium chlorochromate 作用下， 以 乙腈 为溶剂， 反应 1.5h， 以64%的产率得到(2S,3R)-3-acetoxy-2-(2,2-dichloroacetamido)-3-(4-nitrophenyl)propanoic acid
  参考文献：
  名称：

  Synthesis and antimicrobial activity of chloramphenicol–polyamine conjugates

  摘要：

  A series of chloramphenicol (CAM) amides with polyamines (PAs), suitable for structure-activity relationship studies, were synthesized either by direct attachment of the PA chain on the 2-aminopropane- 1,3-diol backbone of CAM, previously oxidized selectively at its primary hydroxyl group, or from chloramphenicol base (CLB) through acylation with succinic or phthalic anhydride and finally coupling with a PA. Conjugates 4 and 5, in which the CLB moiety was attached on N4 and N1 positions, respectively, of the N-8,N-8-dibenzylated spermidine through the succinate linker, were the most potent antibacterial agents. Both conjugates were internalized into Escherichia coli cells by using the spermidine-preferential uptake system and caused decrease in protein and polyamine content of the cells. Noteworthy, conjugate 4 displayed comparable activity to CAM in MRSA or wild-type strains of Staphylococcus aureus and Escherichia coli, but superior activity in E. coli strains possessing ribosomal mutations or expressing the CAM acetyltransferase (cat) gene. Lead compounds, and in particular conjugate 4, have been therefore discovered during the course of the present work with clinical potential. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.069
• 作为产物：
  描述：

  氯霉素 在 咪唑 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.5h， 生成 氯霉素 1-乙酸酯
  参考文献：
  名称：

  Synthesis and antimicrobial activity of chloramphenicol–polyamine conjugates

  摘要：

  A series of chloramphenicol (CAM) amides with polyamines (PAs), suitable for structure-activity relationship studies, were synthesized either by direct attachment of the PA chain on the 2-aminopropane- 1,3-diol backbone of CAM, previously oxidized selectively at its primary hydroxyl group, or from chloramphenicol base (CLB) through acylation with succinic or phthalic anhydride and finally coupling with a PA. Conjugates 4 and 5, in which the CLB moiety was attached on N4 and N1 positions, respectively, of the N-8,N-8-dibenzylated spermidine through the succinate linker, were the most potent antibacterial agents. Both conjugates were internalized into Escherichia coli cells by using the spermidine-preferential uptake system and caused decrease in protein and polyamine content of the cells. Noteworthy, conjugate 4 displayed comparable activity to CAM in MRSA or wild-type strains of Staphylococcus aureus and Escherichia coli, but superior activity in E. coli strains possessing ribosomal mutations or expressing the CAM acetyltransferase (cat) gene. Lead compounds, and in particular conjugate 4, have been therefore discovered during the course of the present work with clinical potential. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.069

文献信息

• Chemoenzymatic Synthesis of Acyl Coenzyme A Substrates Enables <i>in Situ</i> Labeling of Small Molecules and Proteins
  作者：Vinayak Agarwal、Stefan Diethelm、Lauren Ray、Neha Garg、Takayoshi Awakawa、Pieter C. Dorrestein、Bradley S. Moore

  DOI：10.1021/acs.orglett.5b02113

  日期：2015.9.18

  generate fully functional acyl coenzyme A molecules that are then used as substrates to drive in situ acyl transfer reactions is described. Mass spectrometry based assays to verify the identity of acyl coenzyme A enzymatic products are also illustrated. The approach is responsive to a diverse array of carboxylic acids that can be elaborated to their corresponding coenzyme A thioesters, with potential applications

  描述了一种化学酶促方法，其产生全功能的酰基辅酶A分子，然后将其用作底物以驱动原位酰基转移反应。还说明了基于质谱的测定法，以验证酰基辅酶A酶产物的身份。该方法响应于可以修饰为其相应的辅酶A硫酯的各种羧酸，在利用酰基辅酶A底物的广泛化学生物学研究中具有潜在的应用前景。
• Isolation of 3′-O-Acetylchloramphenicol: A possible intermediate in chloramphenicol biosynthesis
  作者：Frank Groß、Elizabeth A. Lewis、Mahmood Piraee、Karl-Heinz van Pée、Leo C. Vining、Robert L. White

  DOI：10.1016/s0960-894x(01)00739-9

  日期：2002.2

  ol, commonly formed from chloramphenicol by resistant bacteria, has been isolated from the antibiotic-producing organism. Biosynthetic experiments suggest that it is a protected intermediate in chloramphenicol biosynthesis, implicating acetylation as a self-resistance mechanism in the producing organism.

  通常从抗生细菌由氯霉素形成的3'-O-乙酰氯霉素已从产生抗生素的生物中分离出来。生物合成实验表明，它是氯霉素生物合成中的一种受保护中间体，暗示乙酰化是生产生物体中的一种自抗性机制。
• Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics
  作者：Shamima Nasrin、Suresh Ganji、Kavita S. Kakirde、Melissa R. Jacob、Mei Wang、Ranga Rao Ravu、Paul A. Cobine、Ikhlas A. Khan、Cheng-Cang Wu、David A. Mead、Xing-Cong Li、Mark R. Liles

  DOI：10.1021/acs.jnatprod.7b00903

  日期：2018.6.22

  A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol (Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acety1-3-butanoyl-chloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol. Cm was used as the selectable antibiotic for cloning, suggesting that heterologously expressed enzymes resulted in derivatization of Cm into new chemical entities with biological activity. An esterase was found to be responsible for the enzymatic regeneration of Cm, and the gene trfA responsible for plasmid copy induction was found to be responsible for inducing antibacterial activity in some clones. Six additional acylchloramphenicols were synthesized for structure and antibacterial activity relationship studies, with 1-p-nitrobenzoylchloramphenicol the most active against Mycobacterium intracellulare and Mycobacterium tuberculosis, with MICs of 12.5 and 50.0 mu g/mL, respectively.
• Enzymatic regioselective production of chloramphenicol esters
  作者：Ayla M.C. Bizerra、Tasso G.C. Montenegro、Telma L.G. Lemos、Maria C.F. de Oliveira、Marcos C. de Mattos、Iván Lavandera、Vicente Gotor-Fernández、Gonzalo de Gonzalo、Vicente Gotor

  DOI：10.1016/j.tet.2011.02.070

  日期：2011.4

  An enzymatic study has been performed in the search for synthetic routes to produce chloramphenicol derivatives through regioselective processes using lipases. Complementary transesterification and hydrolytic reactions have been carried to synthesize chloramphenicol regioisomers. Reaction parameters, such as biocatalyst, solvent, acyl donor, and temperature have been optimised in order to obtain chloramphenicol esters with high yields through acylation processes. Scale-up of the enzymatic reactions (1 g-scale at 0.25 M) and catalyst recycling (up to 10 cycles) have been successfully achieved. Furthermore, monoacylated derivatives at the more hindered secondary position could also be obtained employing hydrolysis processes. (C) 2011 Elsevier Ltd. All rights reserved.