tert-butyl (4S,5S)-5-[N-(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenyl-(E)-2-hexenoate | 160803-09-8

• 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,5S)-5-[N-(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenyl-(E)-2-hexenoate
• 英文别名: tert-butyl (E,4S,5S)-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhex-2-enoate
• CAS: 160803-09-8
• 化学式: C₂₁H₃₁NO₅
• 分子量: 377.481
• InChiKey: IBFXDVTYWSHAGO-CPQFKCLQSA-N

物化性质

• 熔点：
  89-91 °C
• 沸点：
  517.2±50.0 °C(predicted)
• 密度：
  1.095±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4S,5S)-5-[N-(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenyl-(E)-2-hexenoate 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 以84%的产率得到tert-butyl (4S,5S)-5-[N-(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenyl-hexanoate
  参考文献：
  名称：

  Phe-Gly Dipeptidomimetics Designed for the Di-/Tripeptide Transporters PEPT1 and PEPT2:  Synthesis and Biological Investigations

  摘要：

  A series of five Phe-Gly dipeptidomimetics containing different amide bond replacements have been synthesized in a facile way from the readily available unsaturated ketoester 1, and their affinities for the di-/tripeptide transporters hPEPT1 (Caco-2 cells) and rPEPT2 (SKPT cells) were tested. The compounds contained the amide bond isosteres ketomethylene (2a), (R)- and (S)-hydroxyethylidene (3a and 4a), and (R)- and (S)-hydroxyethylene (5a and 6a) to provide information on the conformational and stereochemical requirements for hPEPT1 and rPEPT2 affinity. The affinity studies showed that for rPEPT2 there is no significant difference in affinity between the ketomethylene isostere 2a and the natural substrate Phe-Gly (K-i values of 18.8 and 14.6 muM, respectively). Also the affinities for hPEPT1 are in the same range (K-i values of 0.40 and 0.20 mM, respectively). This corroborates earlier findings that the amide bond as such is not essential for binding to PEPTX, but the results also reveal possible differences in the binding of ketomethylene isosteres to hPEPT1 and rPEPT2. The trans-hydroxyethylidene and hydroxyethylene isosteres proved to be poor substrates for PEPTX. These results provide new information about the importance of flexibility and of the stereochemistry at the C-4-position for this class of compounds. Furthermore, the intracellular uptake of 2a-4a in Caco-2 cells was investigated, showing a 3-fold reduction of the uptake of 2a in the presence of the competetive inhibitor Gly-Pro, indicating contribution from an active transport component. No active uptake of 3a and 4a was observed. Transepithelial. transport studies also indicated active transport of 2a across Caco-2 monolayers.

  DOI：

  10.1021/jm031022+
• 作为产物：
  描述：

  tert-butyl glyoxylate 在 (S)-alpine-hydride 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.17h， 生成 tert-butyl (4S,5S)-5-[N-(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenyl-(E)-2-hexenoate
  参考文献：
  名称：

  Diastereoselective Reduction of a Chiral N-Boc-Protected δ-Amino-α,β-unsaturated γ-Keto Ester Phe-Gly Dipeptidomimetic

  摘要：

  The readily available N-Boc-protected delta-amino alpha,beta-unsaturated gamma-keto ester 1 was diastereoselectively reduced to the corresponding alcohols 2 and 3, using boron- and aluminum-based reducing reagents. Reduction reactions were successful and resulted in anti/syn ratios of alcohols of >95:5 (80% yield), using LiAlH(O-t-Bu)(3) in EtOH at -78degreesC under chelation control, and 5:95 (98% yield), using NB-Enantride in THF at -78degreesC under Felkin-Anh control.

  DOI：

  10.1021/jo020442o

文献信息

• Synthesis of (E)-olefin dipeptide isosteres
  作者：Judi A. McKinney、Daniel F. Eppley、Richard M. Keenan

  DOI：10.1016/0040-4039(94)88055-7

  日期：1994.8

  A route to the synthesis of (E)-olefin dipeptide isosteres is reported. The key step involves an orthoester Claisen rearrangement of an allylic alcohol derived from commercially available amino acids. Chirality transfer from the alcohol center to the newly formed carbon-carbon bond provides a stereocontrolled introduction of the C-terminal aspartic acid“side chain” of the isosteres.

  报道了合成（E）-烯烃二肽等排体的途径。关键步骤涉及衍生自商业氨基酸的烯丙醇的原酸酯克莱森重排。从醇中心向新形成的碳-碳键的手性转移为立体异构体的C末端天冬氨酸“侧链”提供了立体控制的引入。