(-)-(2R)-N-benzyloxycarbonyl-3,3,3-trifluoroalanine | 177469-13-5

• 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: (-)-(2R)-N-benzyloxycarbonyl-3,3,3-trifluoroalanine
• 英文别名: N-Cbz-3,3,3-trifluoroalane；(R)-Z-TFM-Gly-OH；Alanine, 3,3,3-trifluoro-N-[(phenylmethoxy)carbonyl]-；(2R)-3,3,3-trifluoro-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 177469-13-5
• 化学式: C₁₁H₁₀F₃NO₄
• 分子量: 277.2
• InChiKey: JBNIYYRTJUAMKZ-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (-)-(2R)-N-benzyloxycarbonyl-3,3,3-trifluoroalanine 在 palladium dihydroxide 氢气 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以64%的产率得到(R)-2-amino-3,3,3-trifluoropropanoic acid
  参考文献：
  名称：

  New Versatile Fluorinated Chiral Building Blocks:  Synthesis and Reactivity of Optically Pure α-(Fluoroalkyl)-β-sulfinylenamines

  摘要：

  Efficient synthesis of optically pure alpha-(fluoroalkyl)-beta-sulfinyl enamines has been achieved by aza-Wittig reaction of triphenyliminophosphoranes with the corresponding alpha-fluorinated-alpha'-sulfinyl ketones. The title compounds 3,4 showed an overwhelming preference for the Z stereochemistry of the enamine form. Their general reactivity has been studied. The reaction with some electrophiles (i.e. benzyl chloroformate and benzyl and allyl bromide) occurs at the nitrogen atom providing the corresponding N,N-disubstituted enamines. Nucleophiles add smoothly to C-2: heteroatom-centered nucleophiles like methanol, ammonia, and thiophenol afford gem-disubstituted derivatives under thermodynamic control, while a C-centered nucleophile like nitromethane adds in irreversible fashion. The hydride- and deuteride-promoted reduction of 3,4 to the N-Cbz-protected (14) and N-unprotected (15) alpha-fluorinated-alpha'-sulfinyl amines has been studied. Hydride addition was stereoselective, while low stereoselection was obtained with the other tested nucleophiles. Desulfurization of the optically pure 1,1,1-trifluoro-3-sulfinyl amine 15a afforded (R)-1-(trifluoromethyl)ethylamine 17. The Pummerer rearrangement of 14 occurs in an unusual nonoxidative way affording the sulfenamide 24, that readily provided (R)-(2-H)- and -(2-D)-3,3,3-trifluoroalaninol (19) and (R)-3,3,3-trifluoroalanine (22).

  DOI：

  10.1021/jo952097r
• 作为产物：
  描述：

  (-)-(2S,S_S)-2-(N-benzyloxycarbonyl)amino-3,3,3-trifluoropropyl-1-(1-naphtyl)sulfoxide 在 2,4,6-三甲基吡啶 、 ruthenium(IV) oxide 、 sodium periodate 、 potassium carbonate 作用下， 以 水 、 丙酮 、 乙腈 为溶剂， 反应 1.33h， 生成 (-)-(2R)-N-benzyloxycarbonyl-3,3,3-trifluoroalanine
  参考文献：
  名称：

  Enantioselective Synthesis of Fluorinated α-Amino Acids and Derivatives in Combination with Ring-Closing Metathesis:  Intramolecular π-Stacking Interactions as a Source of Stereocontrol

  摘要：

  [GRAPHICS]Hydride reduction of C=N bonds stereocontrolled by intramolecular m-stacking interactions of 1-naphthylsulfinyl and N-aryl groups, nonoxidative Pummerer rearrangement, and ring-closing metathesis are efficiently combined in a highly stereoselective entry to enantiomerically pure cyclic and acyclic fluorinated beta -amino alcohols and alpha -amino acid derivatives, respectively.

  DOI：

  10.1021/ol016087q

文献信息

• Methyl to trifluoromethyl substitution as a strategy to increase the membrane permeability of short peptides
  作者：Takahiro Ono、Kohsuke Aikawa、Takashi Okazoe、Jumpei Morimoto、Shinsuke Sando

  DOI：10.1039/d1ob01565f

  日期：——

  CH₃ to CF₃ substitution on a side chain of proteiogenic amino acids increases the membrane permeability of peptides.

  CH₃到CF₃的取代会增加蛋白质氨基酸侧链的膜通透性。
• DE2806833
  申请人：——

  公开号：——

  公开（公告）日：——
• Untersuchungen zur proteasekatalysierten und chemischen Peptidbindungskn�pfung mit ?-trifluormethylsubstituierten ?-Aminos�uren
  作者：K. Burger、Kerstin M�tze、Wolfgang Hollweck、Beate Koksch、Peter Kuhl、H.-D. Jakubke、J�rgen Riede、Annette Schier

  DOI：10.1002/prac.19933350404

  日期：——

  Subtilisin, alpha-chymotrypsin and papain catalyzed hydrolyses of alpha-trifluoromethyl substituted N-benzyloxycarbonyl amino acid methylesters (Z-TFM-Xaa-OMe) 1 can be achieved only in the case of 3,3,3-trifluoroalanine. Enzymatic incorporation of Z-TFM amino acids 2 into N-terminal position of dipeptides also fails. In contrary, dipeptides with a TFM amino acid moiety in N-terminal position, e. g. TFM-Phg-L-Phe-OMe 5, react with H-Leu-NH2 to give the corresponding tripeptides 6 in high yield. Z protected dipeptide derivatives 8 with N-terminal TFM amino acids can be obtained via 4-trifluoromethyl-5-(4H)-oxazolones 7.
• Enantioselective Synthesis of Fluorinated α-Amino Acids and Derivatives in Combination with Ring-Closing Metathesis:  Intramolecular π-Stacking Interactions as a Source of Stereocontrol
  作者：Santos Fustero、Antonio Navarro、Belén Pina、Juan García Soler、Ana Bartolomé,、Amparo Asensio、Antonio Simón、Pierfrancesco Bravo、Giovanni Fronza、Alessandro Volonterio、Matteo Zanda

  DOI：10.1021/ol016087q

  日期：2001.8.1

  [GRAPHICS]Hydride reduction of C=N bonds stereocontrolled by intramolecular m-stacking interactions of 1-naphthylsulfinyl and N-aryl groups, nonoxidative Pummerer rearrangement, and ring-closing metathesis are efficiently combined in a highly stereoselective entry to enantiomerically pure cyclic and acyclic fluorinated beta -amino alcohols and alpha -amino acid derivatives, respectively.
• New Versatile Fluorinated Chiral Building Blocks:  Synthesis and Reactivity of Optically Pure α-(Fluoroalkyl)-β-sulfinylenamines
  作者：Alberto Arnone、Pierfrancesco Bravo、Silvia Capelli、Giovanni Fronza、Stefano V. Meille、Matteo Zanda、Giancarlo Cavicchio、Marcello Crucianelli

  DOI：10.1021/jo952097r

  日期：1996.1.1

  Efficient synthesis of optically pure alpha-(fluoroalkyl)-beta-sulfinyl enamines has been achieved by aza-Wittig reaction of triphenyliminophosphoranes with the corresponding alpha-fluorinated-alpha'-sulfinyl ketones. The title compounds 3,4 showed an overwhelming preference for the Z stereochemistry of the enamine form. Their general reactivity has been studied. The reaction with some electrophiles (i.e. benzyl chloroformate and benzyl and allyl bromide) occurs at the nitrogen atom providing the corresponding N,N-disubstituted enamines. Nucleophiles add smoothly to C-2: heteroatom-centered nucleophiles like methanol, ammonia, and thiophenol afford gem-disubstituted derivatives under thermodynamic control, while a C-centered nucleophile like nitromethane adds in irreversible fashion. The hydride- and deuteride-promoted reduction of 3,4 to the N-Cbz-protected (14) and N-unprotected (15) alpha-fluorinated-alpha'-sulfinyl amines has been studied. Hydride addition was stereoselective, while low stereoselection was obtained with the other tested nucleophiles. Desulfurization of the optically pure 1,1,1-trifluoro-3-sulfinyl amine 15a afforded (R)-1-(trifluoromethyl)ethylamine 17. The Pummerer rearrangement of 14 occurs in an unusual nonoxidative way affording the sulfenamide 24, that readily provided (R)-(2-H)- and -(2-D)-3,3,3-trifluoroalaninol (19) and (R)-3,3,3-trifluoroalanine (22).