tert-butyl (4S)-4-<(1S)-1-hydroxy-3-phenyl-2-propynyl>-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | 241478-34-2

• 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: tert-butyl (4S)-4-<(1S)-1-hydroxy-3-phenyl-2-propynyl>-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• 英文别名: tert-butyl (4S,1'S)-2,2-dimethyl-4-(1'-hydroxy-3'-phenylprop-2'-ynyl)oxazolidine-3-carboxylate；tert-butyl (4S,1'S)-2,2-dimethyl-4-(1'-hydroxy-3'-phenyl-2'-propynyl)oxazolidine-3-carboxylate；tert-butyl (4S)-4-[(1S)-1-hydroxy-3-phenylprop-2-ynyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 241478-34-2
• 化学式: C₁₉H₂₅NO₄
• 分子量: 331.412
• InChiKey: GMJFVEXSJDRBJS-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (4S)-4-<(1S)-1-hydroxy-3-phenyl-2-propynyl>-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 在 Cu(TBS)2 2,6-二甲基吡啶 、 盐酸 、 三乙基硅烷 、 sodium hydroxide 、 copper(I) bromide dimethylsulfide complex 、 氢气 、 1-羟基苯并三唑 、 N,N-二甲基苯胺 、 乙二胺 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 23.84h， 生成 (1R,2S,3R)-2-[(1S,2S)-1-[tert-butyl(dimethyl)silyl]oxy-2-[[(4R)-2,2-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-thiazolidine-4-carbonyl]amino]butyl]-3-phenylcyclopropane-1-carboxylic acid
  参考文献：
  名称：

  环丙烷衍生的拟肽。设计，合成和评估新型Ras法呢基转移酶抑制剂。

  摘要：

  先前已经建立了三取代的环丙烷作为几种生物系统中二肽阵列的刚性替代品。为了进一步评估这些二肽模拟物在基于Ras farnesyltransferase（FTase）的新型CA（1）A（2）X-基抑制剂的设计中的实用性，该抑制剂是构象受限的非对映体假肽CAbuPsi [COcpCO] FM 7-9，制备类似的CAbuPsi [CHOHCH（2）] FM（10）和四肽CAbuFM（6）。特别设计了两个肽主链取代基和7-9中环丙烷环上的苯基的方向，以探测FTase A（2）子位点疏水结合口袋的选定拓扑特征。必要的三取代环丙烷羧酸22和非对映体环丙基内酯32a的合成，b特色为手性烯丙基重氮乙酸酯的非对映选择性分子内环丙烷化，以及通过用有机铜酸盐打开N-Boc-氮丙啶，将侧链引入环丙烷衍生的二肽取代的C端氨基酸的新方法。然后通过标准肽偶联技术将这些环丙烷中间体转化为靶向的FTase抑制剂7-9。发现伪肽7-9是Ras

  DOI：

  10.1021/jo001257i
• 作为产物：
  描述：

  3-反-溴碳-2,2'-二甲基氧酸酯 、 苯乙炔 在 正丁基锂 、 zinc dibromide 作用下， 以 乙醚 为溶剂， 以69%的产率得到tert-butyl (4S)-4-<(1S)-1-hydroxy-3-phenyl-2-propynyl>-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
  参考文献：
  名称：

  Structure-activity relationship of short-chain sphingoid bases as inhibitors of sphingosine kinase

  摘要：

  Short-chain sphinganine analogues 8, 9, 18, and 19 as well as 3-fluoro-sphingosine analogues 25 and 26 were synthesized. Their potential as sphingosine kinase inhibitors was investigated, in combination with previously synthesized sphingosine and fluorinated sphinganine analogues. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00554-5

文献信息

• Effect of Aromatic Short-Chain Analogues of Ceramide on Axonal Growth in Hippocampal Neurons
  作者：Ilse Van Overmeire、Swetlana A. Boldin、Filip Dumont、Serge Van Calenbergh、Guido Slegers、Denis De Keukeleire、Anthony H. Futerman、Piet Herdewijn

  DOI：10.1021/jm990091e

  日期：1999.7.1

  A series of D-erythro- and L-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B-1 (FB1) on axonal growth in hippocampal neurons. The analogues contained either a C-7 Side chain or a phenyl group substituted for the C-13 residue present in naturally occurring ceramides, while the N-acyl chain length was reduced from C-16-C-24 to C-2-C-8. D-erythro-Ceramide 18a with a C-7 Side chain and an N-acetyl residue and D-erythro-ceramide 20c with an aromatic side chain and an N-hexanoyl residue were most active in reversing the inhibitory effects of FB1 on axonal growth, although the mechanism remains unclear.
• Development of New Carboxylic Acid-Based MMP Inhibitors Derived from Functionalized Propargylglycines
  作者：Michael G. Natchus、Roger G. Bookland、Matthew J. Laufersweiler、Staszek Pikul、Neil G. Almstead、Biswanath De、Michael J. Janusz、Lily C. Hsieh、Fei Gu、Matthew E. Pokross、Vikram S. Patel、Susan M. Garver、Sean X. Peng、Todd M. Branch、Selane L. King、Timothy R. Baker、David J. Foltz、Glen E. Mieling

  DOI：10.1021/jm000477l

  日期：2001.3.1

  A series of carboxylic acids were prepared from a propargylglycine scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for four enzymes within the MMP family. The inhibitors were typically potent against collagenase-3 (MMP-13) and gelatinase A (MMP-2), while they spared collagenase-1 (MMP-1) and only moderately inhibited stromelysin (MMP-3). Compound 40 represents a typical inhibition profile of a compound with reasonable potency. Introduction of polar groups was required in order to generate inhibitors with acceptable water solubility, and this often resulted in a loss of potency as in compound 63. High serum protein binding proved to be a difficult hurdle with many compounds such as 48 showing > 99% binding. Some compounds such as 64 displayed similar to 90% binding, but no reliable method was discovered for designing molecules with low protein binding. Finally, selected data regarding the pharmacokinetic behavior of these compounds is presented.
• Structure-activity relationship of short-chain sphingoid bases as inhibitors of sphingosine kinase
  作者：Steven De Jonghe、Ilse Van Overmeire、Samantha Poulton、Chris Hendrix、Roger Busson、Serge Van Calenbergh、Denis De Keukeleire、Sarah Spiegel、Piet Herdewijn

  DOI：10.1016/s0960-894x(99)00554-5

  日期：1999.11

  Short-chain sphinganine analogues 8, 9, 18, and 19 as well as 3-fluoro-sphingosine analogues 25 and 26 were synthesized. Their potential as sphingosine kinase inhibitors was investigated, in combination with previously synthesized sphingosine and fluorinated sphinganine analogues. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Cyclopropane-Derived Peptidomimetics. Design, Synthesis, and Evaluation of Novel Ras Farnesyltransferase Inhibitors
  作者：Michael C. Hillier、James P. Davidson、Stephen F. Martin

  DOI：10.1021/jo001257i

  日期：2001.3.1

  Trisubstituted cyclopropanes have previously been established as rigid replacements of dipeptide arrays in several biological systems. Toward further evaluating the utility of these dipeptide mimics in the design of novel CA(1)A(2)X-based inhibitors of Ras farnesyltransferase (FTase), the conformationally constrained, diastereomeric pseudopeptides CAbuPsi[COcpCO]FM 7-9, the flexible analogue CAbuPsi[CHOHCH(2)]FM

  先前已经建立了三取代的环丙烷作为几种生物系统中二肽阵列的刚性替代品。为了进一步评估这些二肽模拟物在基于Ras farnesyltransferase（FTase）的新型CA（1）A（2）X-基抑制剂的设计中的实用性，该抑制剂是构象受限的非对映体假肽CAbuPsi [COcpCO] FM 7-9，制备类似的CAbuPsi [CHOHCH（2）] FM（10）和四肽CAbuFM（6）。特别设计了两个肽主链取代基和7-9中环丙烷环上的苯基的方向，以探测FTase A（2）子位点疏水结合口袋的选定拓扑特征。必要的三取代环丙烷羧酸22和非对映体环丙基内酯32a的合成，b特色为手性烯丙基重氮乙酸酯的非对映选择性分子内环丙烷化，以及通过用有机铜酸盐打开N-Boc-氮丙啶，将侧链引入环丙烷衍生的二肽取代的C端氨基酸的新方法。然后通过标准肽偶联技术将这些环丙烷中间体转化为靶向的FTase抑制剂7-9。发现伪肽7-9是Ras