氯霉素O-叔-丁基二甲基硅烷基醚 | 864529-25-9

• 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O-叔-丁基二甲基硅烷基醚
• 英文名称: chloramphenicol
• 英文别名: Chloramphenicol O-tert-Butyldimethylsilyl Ether；N-[(1R,2R)-3-[tert-butyl(dimethyl)silyl]oxy-1-hydroxy-1-(4-nitrophenyl)propan-2-yl]-2,2-dichloroacetamide
• CAS: 864529-25-9
• 化学式: C₁₇H₂₆Cl₂N₂O₅Si
• 分子量: 437.395
• InChiKey: HAFNKEOYFQRWIB-ZIAGYGMSSA-N

物化性质

• 沸点：
  576.0±50.0 °C(Predicted)
• 密度：
  1.240±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、可溶于二氯甲烷、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  3.94
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  氯霉素O-叔-丁基二甲基硅烷基醚 在 四丁基氟化铵 、 四丁基碘化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2,2-Dichloro-N-[1-(4-nitrophenyl)-3-oxoprop-1-en-2-yl]acetamide
  参考文献：
  名称：

  抑制核糖体的抗生素氯霉素的衍生物抑制细菌细胞壁的生物合成

  摘要：

  在这里，我们描述了细菌翻译抑制抗生素氯霉素（CAM）的α，β-不饱和羰基衍生物的制备和评价。与母体抗生素相比，两种含有α，β-不饱和酮的化合物（1和4）对一组革兰氏阳性病原体表现出更广谱的活性，其最低抑菌浓度范围为2–32μg/ mL。有趣的是，与母体CAM不同，这些化合物不会抑制细菌的翻译。显微镜证据和细胞壁肽聚糖的代谢标记表明化合物1和4对金黄色葡萄球菌的包膜造成了广泛破坏通过抑制细胞壁肽聚糖生物合成的早期来抑制细胞的生长。与破坏膜的阳离子阳离子两亲物的作用不同，这些化合物不能迅速渗透细菌膜。像母体抗生素CAM一样，化合物1和4对金黄色葡萄球菌具有抑菌作用。化合物1和4对永生化的有核哺乳动物细胞都具有细胞毒性。但是，它们都没有对哺乳动物的红细胞造成可测量的膜损伤。这些数据表明，所报道的源自CAM的抗微生物剂为开发新型细菌细胞壁生物合成抑制性抗生素提供了新的分子支架。

  DOI：

  10.1021/acsinfecdis.8b00078
• 作为产物：
  描述：

  氯霉素 、 叔丁基二甲基氯硅烷 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 氯霉素O-叔-丁基二甲基硅烷基醚
  参考文献：
  名称：

  抑制核糖体的抗生素氯霉素的衍生物抑制细菌细胞壁的生物合成

  摘要：

  在这里，我们描述了细菌翻译抑制抗生素氯霉素（CAM）的α，β-不饱和羰基衍生物的制备和评价。与母体抗生素相比，两种含有α，β-不饱和酮的化合物（1和4）对一组革兰氏阳性病原体表现出更广谱的活性，其最低抑菌浓度范围为2–32μg/ mL。有趣的是，与母体CAM不同，这些化合物不会抑制细菌的翻译。显微镜证据和细胞壁肽聚糖的代谢标记表明化合物1和4对金黄色葡萄球菌的包膜造成了广泛破坏通过抑制细胞壁肽聚糖生物合成的早期来抑制细胞的生长。与破坏膜的阳离子阳离子两亲物的作用不同，这些化合物不能迅速渗透细菌膜。像母体抗生素CAM一样，化合物1和4对金黄色葡萄球菌具有抑菌作用。化合物1和4对永生化的有核哺乳动物细胞都具有细胞毒性。但是，它们都没有对哺乳动物的红细胞造成可测量的膜损伤。这些数据表明，所报道的源自CAM的抗微生物剂为开发新型细菌细胞壁生物合成抑制性抗生素提供了新的分子支架。

  DOI：

  10.1021/acsinfecdis.8b00078

文献信息

• DIDMH in combination with triflic acid - A new promoter system for thioglycoside glycosyl donors
  作者：Mads Heuckendorff、Henrik H. Jensen

  DOI：10.1016/j.carres.2017.11.012

  日期：2018.1

  We have explored the possibility of using 1,3-diiodo-5,5-dimethylhydantoin (DIDMH) as an alternative to N-iodosuccinimide (NIS) for activation of glycosyl donors of the thioglycoside type in various glycosylation reactions. DIDMH was found to match NIS when it comes to the capability to activate thioglycosides and provide glycosylation products in good yields. Notably, with the two equivalents of reactive

  我们已经探索了在各种糖基化反应中使用1,3-二碘-5,5-二甲基乙内酰脲（DIDMH）替代N-碘琥珀酰亚胺（NIS）来活化硫代糖苷类型糖基供体的可能性。在激活硫糖苷和提供高收率糖基化产物的能力方面，发现DIDMH与NIS相匹配。值得注意的是，每个DIDMH分子具有两个当量的反应性碘鎓离子，因此只需添加较少的质量即可使该活化剂在经济上成为NIS的替代原子。此外，发现DIDMH可以在储存数周后保持稳定，并且价格与NIS相当。掌握了这些知识后，我们因此鼓励糖类社区考虑使用DIDMH在糖基化反应中激活硫糖苷。
• Elucidating absolute configuration of unsaturated alcohols via enantioselective acylation reactions
  作者：Christina M. LeGay、Colton G. Boudreau、Darren J. Derksen

  DOI：10.1039/c3ob40709h

  日期：——

  Enantioselective nucleophilic acylation catalysis provides a simple method of determining absolute configuration for unsaturated alcohols. Extension of this technique to natural products and synthetic compounds, as well as current limitations of this approach, are also described.

  对映选择性核亲电酰化催化提供了一种简单的方法来确定不饱和醇的绝对构型。该技术在自然产品和合成化合物中的扩展以及该方法目前的局限性也进行了描述。
• 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.
• Correlation between Antigen-Combining-Site Structures and Functions within a Panel of Catalytic Antibodies Generated against a Single Transition State Analog
  作者：Ikuo Fujii、Fujie Tanaka、Hideaki Miyashita、Ryuji Tanimura、Keiko Kinoshita

  DOI：10.1021/ja00128a006

  日期：1995.6

  The diversity of the immune response, which can provide a panel of catalytic antibodies with varying degrees of catalytic activity and substrate specificity by immunization with a single hapten,raises the question concerning the extent to which a rationally designed hapten dictates the paratopes for catalytic function in the antigen-combining site. We have investigated the biochemical properties within a panel of six hydrolytic catalytic antibodies elicited against a phosphonate transition state analog 3 and:have examined the correlation between the functions and the antigen-combining-site structures. Although the individual values for k(cat), K-m, and K-TsA (the affinity for the transition state analog) of the six antibodies differed substantially, the transition state analysis (k(cat)/k(uncat) versus K-S/K-TSA) displayed a linear relationship (slope = 0.99) with the four antibodies 6D9, 8D11, 4D5, and 9C10, which have homologous primary amino acid sequences,providing evidence that all of the differential binding energy of the transition state vs the ground state is available for the rate enhancement. This also suggested that these four antibodies catalyze the hydrolysis by variations of the same basic mechanism of transition state stabilization. In antibody 6D9, the difference in free energy between the antibody-catalyzed and uncatalyzed reactions was calculated to be 4.0 kcal/mol, a value that is consistent with the typical binding energy for one hydrogen bond between charged and uncharged groups in enzyme-substrate complexes. On the other hand, antibody 7C8, which has an amino acid sequence different from those of the others, deviated from the linear relationship observed in the transition state analysis, suggesting that catalytic factors other than transition state stabilization, such as a functioning acid or base, are involved in the catalysis. Thus, the difference in the catalytic properties is reflected in the differences in the Fv amino acid sequences. The analysis of the substrate specificity suggested that the catalytic antibodies with highly homologous primary amino acid sequences possess homogeneous binding modes to the substrate or hapten. The three-dimensional molecular model of the antibody 6D9-hapten complex reveals that the phosphonate moiety in the hapten interacts with His (L27d), a catalytic amino acid residue participating in the transition state stabilization in the antibody-catalyzed reactions. This histidine is conserved in the catalytic antibodies 6D9, 8D11, 4B5, and 9C10, and chemical modification by DEPC treatment caused a complete loss of the hydrolytic activity. Although the amino acid sequence of antibody 3G6 is highly homologous to the other four catalytic antibodies; antibody 3G6 has Tyr (L27d), which had reduced activity when modified with tetranitromethane., It is noteworthy that the majority of these catalytic antibodies, generated against a single transition state analog, display high homology in the biochemical and structural properties and catalyze the reaction with the same mechanism expected from designing the transition state analog. These findings emphasize the critical importance of hapten affinity to transition state stabilization and of chemically designing haptens that closely resemble the true transition state for the generation of catalytic antibodies.
• Derivatives of Ribosome-Inhibiting Antibiotic Chloramphenicol Inhibit the Biosynthesis of Bacterial Cell Wall
  作者：Sivan Louzoun Zada、Keith D. Green、Sanjib K. Shrestha、Ido M. Herzog、Sylvie Garneau-Tsodikova、Micha Fridman

  DOI：10.1021/acsinfecdis.8b00078

  日期：2018.7.13

  evidence and metabolic labeling of a cell wall peptidoglycan suggested that compounds 1 and 4 caused extensive damage to the envelope of Staphylococcus aureus cells by inhibition of the early stage of cell wall peptidoglycan biosynthesis. Unlike the effect of membrane-disrupting antimicrobial cationic amphiphiles, these compounds did not rapidly permeabilize the bacterial membrane. Like the parent antibiotic

  在这里，我们描述了细菌翻译抑制抗生素氯霉素（CAM）的α，β-不饱和羰基衍生物的制备和评价。与母体抗生素相比，两种含有α，β-不饱和酮的化合物（1和4）对一组革兰氏阳性病原体表现出更广谱的活性，其最低抑菌浓度范围为2–32μg/ mL。有趣的是，与母体CAM不同，这些化合物不会抑制细菌的翻译。显微镜证据和细胞壁肽聚糖的代谢标记表明化合物1和4对金黄色葡萄球菌的包膜造成了广泛破坏通过抑制细胞壁肽聚糖生物合成的早期来抑制细胞的生长。与破坏膜的阳离子阳离子两亲物的作用不同，这些化合物不能迅速渗透细菌膜。像母体抗生素CAM一样，化合物1和4对金黄色葡萄球菌具有抑菌作用。化合物1和4对永生化的有核哺乳动物细胞都具有细胞毒性。但是，它们都没有对哺乳动物的红细胞造成可测量的膜损伤。这些数据表明，所报道的源自CAM的抗微生物剂为开发新型细菌细胞壁生物合成抑制性抗生素提供了新的分子支架。