(S)-4-(1-methylethyl)-3-(1-oxopropyl)-5,5-diphenyloxazolidin-2-one | 213887-84-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-4-(1-methylethyl)-3-(1-oxopropyl)-5,5-diphenyloxazolidin-2-one
• 英文别名: (S)-5,5-Diphenyl-4-isopropyl-3-(1'-oxopropyl)-1,3-oxazolidin-2-one；(S)-4-isopropyl-5,5-diphenyl-3-propionyloxazolidin-2-one；(4S)-5,5-diphenyl-3-propanoyl-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 213887-84-4
• 化学式: C₂₁H₂₃NO₃
• 分子量: 337.419
• InChiKey: RQFKFTFTDKLVMZ-IBGZPJMESA-N

物化性质

• 沸点：
  488.8±45.0 °C(Predicted)
• 密度：
  1.147±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  (S)-4-(1-methylethyl)-3-(1-oxopropyl)-5,5-diphenyloxazolidin-2-one 在 lithium hydroxide 、 正丁基锂 、 双氧水 、 zinc dibromide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 26.5h， 生成 (S)-3-acetyl-4-isopropyl-5,5-diphenyloxazolidin-2-one
  参考文献：
  名称：

  A Useful Modification of theEvans Auxiliary: 4-Isopropyl-5,5-diphenyloxazolidin-2-one

  摘要：

  The 4-isopropyl-5,5-diphenyloxazolidinone (1) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250 degrees, a low solubility in most organic solvents, and a C=O group which is sterically protected from nucleophilic attack. Thus; the soluble N-acyl-oxazolidinones (7-16) can be prepared from 1 with BuLi at temperatures around 0 degrees instead of - 78 degrees (Scheme 3): their Li enolates can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be achieved with NaOH at ambient temperatures (Scheme 12),with facile recovery of the precipitating auxiliary 1 (filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from 1 have been investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4 + 2) cycloaddition (Scheme II). The well-known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher melting points and a much more pronounced crystallization tendency than those derived from conventional oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensated by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TICl4 complex of an oxazolidinone are described and discussed in view of the diastereoselective-reaction mechanisms.

  DOI：

  10.1002/(sici)1522-2675(19981111)81:11<2093::aid-hlca2093>3.0.co;2-x
• 作为产物：
  描述：

  L-缬氨酸甲酯 在 sodium hydroxide 、 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 (S)-4-(1-methylethyl)-3-(1-oxopropyl)-5,5-diphenyloxazolidin-2-one
  参考文献：
  名称：

  A Useful Modification of theEvans Auxiliary: 4-Isopropyl-5,5-diphenyloxazolidin-2-one

  摘要：

  The 4-isopropyl-5,5-diphenyloxazolidinone (1) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250 degrees, a low solubility in most organic solvents, and a C=O group which is sterically protected from nucleophilic attack. Thus; the soluble N-acyl-oxazolidinones (7-16) can be prepared from 1 with BuLi at temperatures around 0 degrees instead of - 78 degrees (Scheme 3): their Li enolates can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be achieved with NaOH at ambient temperatures (Scheme 12),with facile recovery of the precipitating auxiliary 1 (filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from 1 have been investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4 + 2) cycloaddition (Scheme II). The well-known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher melting points and a much more pronounced crystallization tendency than those derived from conventional oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensated by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TICl4 complex of an oxazolidinone are described and discussed in view of the diastereoselective-reaction mechanisms.

  DOI：

  10.1002/(sici)1522-2675(19981111)81:11<2093::aid-hlca2093>3.0.co;2-x

文献信息

• Thermal proteome profiling efficiently identifies ribosome destabilizing oxazolidinones
  作者：Christina Nöcker、Nadine Kaiser、Daniel Foley、Sonja Sievers、Petra Janning、Herbert Waldmann、Luca Laraia

  DOI：10.1016/j.tet.2021.132118

  日期：2021.5

  Identifying the targets of bioactive small molecules is a challenging endeavor for which no general solution currently exists. Classical affinity purification experiments suffer from the need to functionalise a bioactive compound and link it to a solid support, which may interfere with target binding. A modern mass spectrometry-based proteomics technique that has partially circumvented this problem

  鉴定具有生物活性的小分子的靶标是一项具有挑战性的工作，目前尚无通用的解决方案。经典的亲和纯化实验需要功能化生物活性化合物并将其连接到固体支持物上，这可能会干扰靶标结合。基于现代质谱的蛋白质组学技术已部分规避了此问题，是热蛋白质组分析（TPP），它同时确定了未修饰的小分子对整个蛋白质组的热稳定性的影响。在这里，我们使用TPP来识别基于经常用作手性助剂的恶唑烷酮的新发现的自噬抑制剂的作用方式。出乎意料的是，发现所有核糖体蛋白中有很大一部分被抑制剂破坏了稳定性，
• Anguinomycins and Derivatives: Total Syntheses, Modeling, and Biological Evaluation of the Inhibition of Nucleocytoplasmic Transport
  作者：Simone Bonazzi、Oliv Eidam、Stephan Güttinger、Jean-Yves Wach、Ivo Zemp、Ulrike Kutay、Karl Gademann

  DOI：10.1021/ja9097093

  日期：2010.2.3

  polyketide natural products anguinomycin C and D is reported based on key steps such as Negishi stereoinversion cross coupling, Jacobsen Cr(III)-catalyzed Hetero Diels-Alder reaction, Evans B-mediated syn-aldol chemistry, and B-alkyl Suzuki-Miyaura cross coupling. The configuration of both natural products was established as (5R,10R,16R,18S,19R,20S). Biological evaluation demonstrated that these natural

  基于 Negishi 立体反转交叉偶联、Jacobsen Cr(III)-催化的 Hetero Diels-Alder 反应、Evans B 介导的 Syn-aldol 化学和 B-烷基等关键步骤，报道了聚酮化合物天然产物 Anguinomycin C 和 D 的制备铃木-宫浦交叉联轴器。两种天然产物的构型均建立为（5R、10R、16R、18S、19R、20S）。生物学评估表明，这些天然产物是核输出受体 CRM1 的抑制剂，导致 CRM1 介导的核蛋白输出在浓度高于 10 nM 时关闭。已经制备了 Anguinomycin 和 Leptomycin B (LMB) 的类似物，具有截短聚酮链的简单 α,β-不饱和内酯类似物 4 保留了大部分生物活性（抑制高于 25 nM）。
• Highly effective and recyclable chiral auxiliaries: a study of the synthesis and use of three 4-isopropyl-5,5-diaryloxazolidin-2-ones
  作者：Karen Alexander (née Gillon)、Stuart Cook、Colin L. Gibson、Alan R. Kennedy†

  DOI：10.1039/b102020j

  日期：——

  A series of three 5,5-diaryl substituted oxazolidin-2-ones (diphenyl, dinaphthyl and ditolyl) have been synthesised. Studies on the benzylation of the lithium enolates of N-acyl derivatives reveal that the yields obtained were sensitive to the method of quenching the reaction. This was particularly acute for the 5,5-diphenyl system where effective yields (69%) and high diastereoselectivities (dr 98 ∶ 2)

  已经合成了一系列三个5，5-二芳基取代的恶唑烷-2-酮（二苯基，二萘基和二甲苯基）。对N-酰基衍生物的烯醇锂的苄基化的研究表明，所获得的收率对淬灭反应的方法很敏感。对于5,5-二苯系统来说尤其如此，仅当将反应淬灭到水性缓冲液中时，才能观察到有效收率（69％）和高非对映选择性（dr 98：2）。对N-酰基衍生物的甲基化研究表明， 只有使用烯醇钠才能观察到最有利的结果（58-69％，博士 91：9）。5,5-ditolyl-4-isopropyloxazolidin-2-one被证明在效率和非对映选择性方面更有效（dr  97：3）。随后，烷基化产物的简单碱性水解允许5,5-二芳基取代的恶唑烷-2--2-酮的高回收率和可回收性，而没有任何有害的环内裂解。另外，从碱性水解中以高收率回收了酰基部分，而没有任何外消旋化的迹象。
• Probing the Influence of an Allylic Methyl Group in Zearalenone Analogues on Binding to Hsp90
  作者：Christian Rink、Florenz Sasse、Asta Zubrienė、Daumantas Matulis、Martin E. Maier

  DOI：10.1002/chem.201001752

  日期：2010.12.27

  Carreira acetylide addition. Further routine steps led to the sulfones 29 and 45, respectively. After merging them with 2‐bromobenzaldehyde 9 in a Julia–Kocienski reaction, metalation, carboxylation, and protecting‐group manipulations gave the seco acids 35 and 49. By means of lactonization under Mitsunobu (alcohol activation) or Trost–Kita conditions (carboxyl activation), all four possible macrocyclic ketone

  通过有机合成用丙酸酯代替乙酸盐，制备了一系列具有烯丙基甲基的玉米赤霉烯酮类似物。为了合成类似物的脂肪族区域，我们使用了不对称烷基化反应生成了戊烯醇衍生物16和ent - 16。通过硼氢化反应，确保了相应的醛。通过加入Carreira乙炔化物将它们与2-戊炔醇衍生物23偶联。进一步的常规步骤分别导致了砜29和45。将它们与2-溴苯甲醛9合并后在一个朱莉娅- Kocienski所反应，金属化，羧化，和保护基团的操作，得到开环酸35和49。通过在Mitsunobu（酒精活化）或Trost-Kita条件（羧基活化）下进行内酯化，可以得到所有四种可能的大环酮立体异构体。总之，考虑各种保护基团的装饰品，获得和细胞毒性（L929小鼠成纤维细胞系）测试16点的类似物。而大多数类似物比玉米赤霉烯酮活性较低（IC 50 = 9.4μ中号），间苯二酚衍生物是可比的，用一种立体异构体（40b中）为稍微更活性（IC
• A study of 4-substituted 5,5-diaryl oxazolidin-2-ones as efficacious chiral auxiliaries
  作者：Colin L. Gibson、Karen Gillon、Stuart Cook

  DOI：10.1016/s0040-4039(98)01412-9

  日期：1998.9

  A series of three 5,5-diaryl substituted oxazolidin-2-ones (diphenyl, dinaphthyl and ditolyl) have been prepared and shown to be particularly effective chiral auxiliaries to afford high yields and diastereoselectivities for alkylation and azidations of their N-acyl derivatives. The 5,5-ditolyl oxazolidin-2-one proved to be particularly efficacious in terms of diastereoselectivity, yield and solubility

  已经制备了一系列的三个5，5-二芳基取代的恶唑烷-2-酮（二苯基，二萘基和二甲苯基），并且显示出是特别有效的手性助剂，以为其烷基化和叠氮化其N-酰基衍生物提供高收率和非对映选择性。在非对映选择性，产率和溶解度方面，证明5，5-二甲苯基恶唑烷-2-酮是特别有效的。