Ethyl 4(S)-benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate | 158744-40-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Ethyl 4(S)-benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate
• 英文别名: tert-butyl (4S,5R)-4-benzyl-5-(2-ethoxy-2-oxoethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 158744-40-2
• 化学式: C₂₁H₃₁NO₅
• 分子量: 377.481
• InChiKey: GSTISRJMVFPJEZ-DLBZAZTESA-N

物化性质

• 沸点：
  453.2±30.0 °C(Predicted)
• 密度：
  1.082±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 4(S)-benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate 在 palladium on activated charcoal N-乙基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 氢氧化钾 、 sodium hydroxide 、 草酰氯 、 三氯溴甲烷 、 氢气 、 2-mercaptopyridine-1-oxide sodium salt 、 溶剂黄146 、 1-羟基苯并三唑一水物 、 N,N-二甲基甲酰胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 异丙醇 、 甲苯 为溶剂， 反应 148.0h， 生成 沙喹那韦
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 在 sodium tetrahydroborate 、 对甲苯磺酸 、 N,N'-羰基二咪唑 作用下， 以 乙醇 为溶剂， 反应 32.0h， 生成 Ethyl 4(S)-benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026

文献信息

• Chemical study on hapalosin, a cyclic depsipeptide possessing multidrug resistance reversing activities: Synthesis, structure and biological activity
  作者：Toshiaki Okuno、Ken Ohmori、Shigeru Nishiyama、Shosuke Yamamura、Kensuke Nakamura、K.N. Houk、Kazuya Okamoto

  DOI：10.1016/0040-4020(96)00951-9

  日期：1996.11

  Hapalosin 1 possessing a multidrug resistance reversing activity, has been synthesized from the corresponding hydroxy acids A, C and γ-amino acid B. The stereochemistry of the natural product 1 and N-demethylhapalosin 11 is discussed by means of spectroscopic manner as well as molecular modeling studies. Biological evaluation of 1 and 11 indicated that a cis-amide function is a crucial factor for the

  由相应的羟基酸A，C和γ-氨基酸B合成了具有多重耐药逆转活性的Hapalosin 1。天然产物1和N-demethylhapalosin 11的立体化学通过光谱学方法以及分子建模研究进行了讨论。对1和11的生物学评估表明，顺式酰胺功能是MDR逆转活性的关键因素。
• HIV Protease Inhibitors Part 2: [3+2] Cycloaddition, Isomerization; and Ring Expansion en route to 4,5-Substituted Cyclohexenones
  作者：Emmanuel Demont、Andrew Eatherton、Christopher S. Frampton、Irfan Kahn、Sally Redshaw

  DOI：10.1055/s-2004-815439

  日期：——

  4,5-Substituted cyclohexanone 10 and its derivatives are carbocyclic analogues of Indinavir 3 and are expected to have antiviral activity. Early attempts to obtain these compounds via a dia­stereoselective [3+2] cycloaddition between 19 and 14 failed due to the sensitivity of the cycloadduct 24. It proved possible to obtain 30 from the α,β-unsaturated ester 27: [3+2] cycloaddition, isomerization, and ring expansion provided α,β-unsaturated ketone 31 from ester 26 in good yields. Further transformations of 31 gave the ­hydroxyethylamino inhibitor analogues of Indinavir 3.

  4,5-取代环己酮 10 及其衍生物是茚地那韦 3 的碳环类似物，有望具有抗病毒活性。早期尝试通过 19 和 14 之间的非对映选择性 [3+2] 环加成来获得这些化合物，但由于环加成物 24 的敏感性而失败。事实证明，可以从δ,δ-不饱和酯 27 中得到 30：通过[3+2]环加成、异构化和扩环，可以从酯 26 中得到δ,δ-不饱和酮 31，而且收率很高。进一步转化 31 得到了茚地那韦 3 的羟乙氨基抑制剂类似物。
• Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
  作者：Kevin E. B. Parkes、David J. Bushnell、Peter H. Crackett、Stephen J. Dunsdon、Andrew C. Freeman、Michelle P. Gunn、Richard A. Hopkins、Robert W. Lambert、Joseph A. Martin

  DOI：10.1021/jo00092a026

  日期：1994.7

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.