(4S)-3-(2-methylene-1-oxohexyl)-4-(phenylmethyl)-2-oxazolidinone | 478912-40-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4S)-3-(2-methylene-1-oxohexyl)-4-(phenylmethyl)-2-oxazolidinone
• 英文别名: (S)-3-(2-methylenehexanoyl)-4-benzyloxazolidin-2-one；4-benzyl-3-(2-butyl-acryloyl)-oxazolidin-2-one；(4S)-4-benzyl-3-(2-methylidenehexanoyl)-1,3-oxazolidin-2-one
• CAS: 478912-40-2
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: ITXPNBGDJSQYEH-HNNXBMFYSA-N

物化性质

• 沸点：
  393.6±25.0 °C(Predicted)
• 密度：
  1.129±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S)-3-(2-methylene-1-oxohexyl)-4-(phenylmethyl)-2-oxazolidinone 在 对甲苯磺酸 、 potassium hydroxide 作用下， 以 乙酸乙酯 为溶剂， 反应 23.5h， 生成 N-[2-(4-benzyl-2-oxo-oxazolidine-3-carbonyl)-hexyl]-N-benzyloxy-formamide
  参考文献：
  名称：

  一种新型肽去甲酰基酶抑制剂的实用对映选择性合成。

  摘要：

  肽去甲酰基酶抑制剂LBM415，（2 S）-N-（5-氟-1-氧化-2-吡啶基）-1-[（2 R）-2-[（甲酰基羟氨基）甲基] -1-的实用合成描述了氧己基] -2-吡咯烷甲酰胺，镁盐11。关键的手性中间体，（2 S）-N-（5-氟-2-吡啶基）-1-[（2 R）-2-[[甲酰基（苯基甲氧基）氨基]甲基] -1-氧己基] -2-吡咯烷甲酰胺8，按与相应的氨基酸偶联制成7与甲酰胺25从制备升-脯氨酸和2-氨基-5-氟吡啶。吡啶氮氧化后，对苄基进行选择性氢解得到原料药的游离酸，将其用氯化镁原位转化为镁盐。得到的产物的总产率为16％，ee＞ 99％。

  DOI：

  10.1021/op050165y
• 作为产物：
  描述：

  正丁基丙二酸二乙酯 在 正丁基锂 、 二乙胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 4.0h， 生成 (4S)-3-(2-methylene-1-oxohexyl)-4-(phenylmethyl)-2-oxazolidinone
  参考文献：
  名称：

  Synthesis, antibacterial activity, and biological evaluation of formyl hydroxyamino derivatives as novel potent peptide deformylase inhibitors against drug-resistant bacteria

  摘要：

  Peptide deformylase (PDF) has been identified as a promising target for novel antibacterial agents. In this study, a series of novel formyl hydroxyamino derivatives were designed and synthesized as PDF inhibitors and their antibacterial activities were evaluated. Among the potent PDF inhibitors (1o, 1q, 1o', 1q', and 1x), in vivo studies showed that compound 1q possesses mild toxicity, a good pharmacokinetic profile and protective effects. The good in vivo efficacy and low toxicity suggest that this class of compounds has potential for development and use in future antibacterial drugs. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.07.106

文献信息

• N-Formyl Hydrozyamine Compounds
  申请人：Lee Kwangho

  公开号：US20090062537A1

  公开（公告）日：2009-03-05

  Novel N-formyl hydroxylamine compounds and their derivatives are disclosed. These N-formyl hydroxylamine compounds inhibit peptidyl deformylase (PDF), an enzyme present in prokaryotes. The compounds are useful as antimicrobials and antibiotics. The compounds of the invention display selective inhibition of peptidyl deformylase versus other metalloproteinases such as MMPs. Methods of preparation and use of the compounds are also disclosed.

  本发明公开了新型N-甲酰基羟胺化合物及其衍生物。这些N-甲酰基羟胺化合物可以抑制肽脱甲酰酶（PDF），该酶存在于原核生物中。这些化合物作为抗菌素和抗生素具有用途。本发明的化合物对肽脱甲酰酶相对于其他金属蛋白酶如MMPs表现出了选择性抑制作用。还公开了这些化合物的制备方法和用途。
• β-Amino Amides from β-Lactams: Application to the Formal Synthesis of a Peptide-Deformylase Inhibitor
  作者：Kapa Prasad、Xinglong Jiang、Mahavir Prashad、Joel Slade、Oljan Repič、Thomas Blacklock

  DOI：10.1055/s-2006-951499

  日期：2006.11

  A facile and a practical synthesis of peptide-deformylase inhibitor 1 is described using an acid-catalyzed aminolysis of β-lactam 12 with pyrrolidine 6 as the key transformation. In addition, simplified conditions for the conversion of a β-hydroxy acid to a β-lactam are reported.

  描述了一种简单且实用的肽去甲酰化酶抑制剂1的合成方法，该方法使用酸催化的氨基醇解反应，将β-内酰胺12与哌啶6作为关键转化。此外，还报告了将β-羟酸转化为β-内酰胺的简化条件。
• [EN] PROCESS FOR PREPARING INTERMEDIATES USEFUL TO PREPARE CERTAIN ANTIBACTERIAL N-FORMYL HYDROXYLAMINES<br/>[FR] PROCEDE DE PREPARATION D'INTERMEDIAIRES SERVANT A PREPARER CERTAINES N-FORMYLE HYDROXYLAMINES ANTIBACTERIENNES
  申请人：NOVARTIS AG

  公开号：WO2005000835A1

  公开（公告）日：2005-01-06

  The present invention is directed to a process for preparing intermediates that are useful to prepare certain antibacterial N-formyl hydroxylamine compounds which are peptide deformylase inhibitors.

  本发明涉及一种用于制备中间体的方法，这些中间体可用于制备特定的抗菌N-甲酰羟胺化合物，这些化合物是肽去甲酰化酶抑制剂。
• WO2007/77186
  申请人：——

  公开号：——

  公开（公告）日：——
• Peptide deformylase inhibitors of Mycobacterium tuberculosis: Synthesis, structural investigations, and biological results
  作者：Arkadius Pichota、Jeyaraj Duraiswamy、Zheng Yin、Thomas H. Keller、Jenefer Alam、Sarah Liung、Gladys Lee、Mei Ding、Gang Wang、Wai Ling Chan、Mark Schreiber、Ida Ma、David Beer、Xinyi Ngew、Kakoli Mukherjee、Mahesh Nanjundappa、Jeanette W.P. Teo、Pamela Thayalan、Amelia Yap、Thomas Dick、Wuyi Meng、Mei Xu、James Koehn、Shi-Hao Pan、Kirk Clark、Xiaoling Xie、Carolyn Shoen、Michael Cynamon

  DOI：10.1016/j.bmcl.2008.10.040

  日期：2008.12

  Bacterial peptide deformylase (PDF) belongs to a subfamily of metalloproteases catalyzing the removal of the N-terminal formyl group from newly synthesized proteins. We report the synthesis and biological activity of highly potent inhibitors of Mycobacterium tuberculosis (Mtb) PDF enzyme as well as the first X-ray crystal structure of Mtb PDF. Structure-activity relationship and crystallographic data clarified the structural requirements for high enzyme potency and cell based potency. Activities against single and multi-drug-resistant Mtb strains are also reported.