phenylmethyl (S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-5-hexenoate | 141362-38-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: phenylmethyl (S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-5-hexenoate
• 英文别名: Benzyl 2(S)-<(tert-butoxycarbonyl)amino>hex-5-enoate；benzyl (S)-2-((tert-butoxycarbonyl)amino)hex-5-enoate；benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hex-5-enoate
• CAS: 141362-38-1
• 化学式: C₁₈H₂₅NO₄
• 分子量: 319.401
• InChiKey: POLPKBFYDHURKE-HNNXBMFYSA-N

物化性质

• 沸点：
  440.2±45.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  phenylmethyl (S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-5-hexenoate 在 9-borabicyclo[3.3.1]nonane dimer 、 4 Angstroems MS 、 phosphorus pentoxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 pyridinium chlorochromate 、 三氟乙酸 、 barium(II) oxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 phenylmethyl (2S)-1,2,3,4-tetrahydro-1-<carbonyl>-2-pyridinecarboxylate
  参考文献：
  名称：

  从常见的中间体合成血管紧张素转换酶抑制剂（-）-A58365A和（-）-A58365B。

  摘要：

  由亚基9和10合成了血管紧张素转化酶抑制剂（-）-A58365A（1）和（-）-A58365B（2），它们被偶联，并且将得到的各个酰胺17a，b转化。通过臭氧分解成醛18a，b，然后进行环脱水成酰胺19a，b。用锡烷处理有助于产生乙烯基锡烷20a，b，通过原甲酸酯化和臭氧分解从中产生酮22a，b。然后进行碱处理和氢解，得到（-）-A58365A（1）。中间体17a，b也通过硼氢化和氧化转化为醛26a，b，然后应用与（-）-A58365A相似的序列，以完成同类物（-）-的第一对映体特异性合成。 A58365B（2）。

  DOI：

  10.1021/jo9822941
• 作为产物：
  描述：

  N-叔丁氧羰基-L-丝氨酸 在 吡啶 、 碘 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 phenylmethyl (S)-2-<<(1,1-dimethylethoxy)carbonyl>amino>-5-hexenoate
  参考文献：
  名称：

  Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors

  摘要：

  Macrocyclization has been frequently utilized for optimizing peptide or peptidomimetic-based compounds. In an attempt to obtain potent, metabolically stable, and orally available proteasome inhibitors, 30 oprozomib-derived macrocyclic peptides with structural diversity in their N-terminus and linker were successively designed and synthesized for structure- activity relationship (SAR) studies. As a consequence, the macrocyclic peptides with N-methyl-pyrazole (24p, 24x), imidazole (24t), and pyrazole (24v) as their respective N-termini exhibited favorable in vitro activity and metabolic stability, which translated into their potent in vivo proteasome inhibitory activity after oral administration. In particular, compound 24v, as the most distinguished one among this series, displayed excellent chymotrypsin-like (ChT-L, beta 5) inhibitory potency (IC50 = 16 nM), low nanomolar antiproliferative activity against all three of the tested cell lines, and superior metabolic stability in mouse liver microsome (MLM), as well as favorable inhibition against ChT-L compared to that of oprozomib in BABL/c mice following po administration at a comparatively low dose, thereby representing a promising candidate for further development.

  DOI：

  10.1021/acs.jmedchem.8b00819

文献信息

• Preparation of enantiomerically pure protected unsaturated α-amino acids from a new serine derived zinc–copper reagent
  作者：Michael J. Dunn、Richard F. W. Jackson

  DOI：10.1039/c39920000319

  日期：——

  Treatment of the iodoalanine derived zinc reagent 1 with Knochel's soluble copper salt (CuCN·2LiCl) allows the preparation of a reactive copper reagent 2 which couples in moderate to good yield with allyl halides to give protected unsaturated α-amino acids in a single step from easily available precursors.

  利用碘丙氨酸衍生的锌试剂1与Knochel可溶性铜盐（CuCN·2LiCl）处理，可制备出一种活性铜试剂2，该试剂与烯丙基卤化物在温和至良好的产率下偶联，可从易获得的起始物直接一步合成得到保护的不饱和α-氨基酸。
• Cross metathesis-mediated synthesis of hydroxamic acid derivatives
  作者：Shital Kumar Chattopadhyay、Subhankar Ghosh、Suman Sil

  DOI：10.3762/bjoc.14.285

  日期：——

  An alternative synthesis of α,ß-unsaturated hydroxamates via cross metathesis between a class-I olefin and N-benzyloxyacrylamide is reported. The reaction proceeds better in the presence of Grubbs' second generation catalyst within short time and in good yields (57-85%) with a range of substrates. Subsequent hydrogenation of each of the CM products delivers the title compounds in moderate to very good

  据报道，通过I类烯烃和N-苄氧基丙烯酰胺之间的交叉复分解，可以合成α，ß-不饱和异羟肟酸酯。在格拉布斯第二代催化剂的存在下，该反应在短时间内以多种底物在较高收率下（57-85％）更好地进行。随后，每种CM产品的氢化反应都会以中等至非常高的收率（70-89％）提供标题化合物。该协议的一个重要证明是生物活性环状肽Chap-31的异常氨基酸成分的制备。
• Synthesis of Enantiomerically Pure Unsaturated .alpha.-Amino Acids Using Serine-Derived Zinc/Copper Reagents
  作者：Michael J. Dunn、Richard F. W. Jackson、Joerg Pietruszka、Debra Turner

  DOI：10.1021/jo00112a048

  日期：1995.4

  Treatment of the serine-derived organozinc reagent 2, in benzene/dimethylacetamide, with a THF solution of CuCN . 2LiCl gives rise to a zinc/copper reagent 6 which reacts directly with allylic halides and tosylates to give the corresponding enantiomerically pure substitution products 9 in 32-65% yield (11 examples). The reaction proceeds by formal S(N)2' displacement of the leaving group. Reaction with propargyl halides gives the corresponding terminal allene 12a. The zinc reagent 2 may also be prepared directly from protected iodoalanine 1 in THP by the Knochel method. Reaction with propargylic tosylates as electrophiles gives rise to the corresponding protected terminal allenic amino acids in 51-81% yield (four examples); use of enantiomerically enriched propargylic tosylates results in the formation of diastereoisomerically enriched allenic products. Reactions of the zinc/copper reagent 6 with a range of representative electrophiles is explored; use of relatively reactive electrophiles is necessary to obtain satisfactory yields. Finally, the possibility of using the serine-derived iodide 20, in which the carboxylic acid is protected as a methyl ester, is established: This reagent offers advantages over the corresponding benzyl ester protected reagent 6 for the synthesis of unsaturated amino acids.