4(S)-Benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetic acid | 158895-85-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4(S)-Benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetic acid
• 英文别名: 2-[(4S,5R)-4-benzyl-2,2-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-oxazolidin-5-yl]acetic acid
• CAS: 158895-85-3
• 化学式: C₁₉H₂₇NO₅
• 分子量: 349.427
• InChiKey: YYSQQCFVUDILRY-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4(S)-Benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetic acid 在 palladium on activated charcoal N-乙基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 氢氧化钾 、 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 130.0h， 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：

  Ethyl 4(S)-benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetate 在 sodium hydroxide 作用下， 生成 4(S)-Benzyl-3-(tert-butoxycarbonyl)-2,2-dimethyl-5(R)-oxazolidineacetic acid
  参考文献：
  名称：

  具有多药耐药逆转活性的环状十肽肽haloposin的化学研究：合成，结构和生物学活性

  摘要：

  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。

  DOI：

  10.1016/0040-4020(96)00951-9

文献信息

• Synthetic study on hapalosin, a cyclic depsipeptide possessing multidrug resistance reversing activities
  作者：Ken Ohmori、Toshiaki Okuno、Shigeru Nishiyama、Shosuke Yamamura

  DOI：10.1016/0040-4039(96)00592-8

  日期：1996.5

  Hapalosin possessing a multidrug resistance reversing activity, has been synthesized from the corresponding hydroxy acids and γ-amino acids. The stereochemistry of the natural product and related derivatives is discussed.

  由相应的羟基酸和γ-氨基酸合成了具有多重耐药逆转活性的Hapalosin。讨论了天然产物和相关衍生物的立体化学。
• 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。
• 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.