N^α-<(tert-butyloxy)carbonyl>-L-2-(9-fluorenyl)glycine | 138566-23-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N^α-<(tert-butyloxy)carbonyl>-L-2-(9-fluorenyl)glycine
• 英文别名: (S)-2-(N-tert-butoxycarbonylamino)-2-(9-fluorenyl)acetic acid；N-Boc-L-fluorenylglycine；(2S)-2-(9H-fluoren-9-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid
• CAS: 138566-23-1
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: GSODHVQZXQVIPW-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.63
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  BOC-甘氨酸 、 BOC-L-亮氨酸 、 Boc-L-蛋氨酸 、 N^α-<(tert-butyloxy)carbonyl>-L-2-(9-fluorenyl)glycine 、 alkaline earth salt of/the/ methylsulfuric acid 生成 8>SP
  参考文献：
  名称：

  Tachykinin NK-1 receptor probed with constrained analogues of substance P

  摘要：

  The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e. L-tetrahydroisoquinoleic acid (Tie), L-fluorenylglycine (Flg), L-diphenylalanine (Dip), the diastereoisomers of L-1-indanylglycine (Ing) and L-benz[f]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylalanine (Delta(Z)Phe, Delta(E)Phe, Delta(Z)Nal, Delta(E)Nal) and L-o,o'-dimethylphenylalanine (Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S-7 and S-8 subsites, corresponding to residues Phe(7) and Phe(8) of substance P. According to the binding potencies of these substituted-SP analogues, the S-7 binding subsite is smaller than the S-8 subsite: the S-7 subsite accepts only one aromatic nucleus, while the S-8 can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S, binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu(6), Pro(9)]SP(6-11), discrepancies are observed between affinity (K-i) and activity (EC(50)) values for IPs production. While a weak correlation between K-i and EC(50) values for IPs production could be found (r=0.70), an excellent correlation could be demonstrated between their affinities (K-i) and their potencies (EC(50)) for cAMP production (r=0.97). The high potency (EC(50)) observed for 'septide-like' molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC(50) values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r=0.94). Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0968-0896(96)00230-1
• 作为产物：
  描述：

  N-(diphenylmethylene)-L-2-(9-fluorenyl)glycinesultam 在 盐酸 、 lithium hydroxide 、 四丁基溴化铵 、 silica gel 、 碳酸氢钠 、 lithium bromide 作用下， 以 乙醇 、 氯仿 、 乙腈 为溶剂， 反应 10.0h， 生成 N^α-<(tert-butyloxy)carbonyl>-L-2-(9-fluorenyl)glycine
  参考文献：
  名称：

  Asymmetric synthesis of L-diphenylalanine and L-9-fluorenylglycine via room temperature alkylations of a sultam-derived glycine imine

  摘要：

  L-diphenylalanine and L-9-fluorenylglycine were prepared from a sultam-derivated glycine imine 3 via room temperature-asymmetric-alkylation/ hydrolysis/mild-sultam-clivage. The L-configuration was ascertained using an X-ray analysis of the alkylation product 4b.

  DOI：

  10.1016/0040-4039(91)80217-t

文献信息

• Design and Synthesis of Side-Chain Conformationally Restricted Phenylalanines and Their Use for Structure-Activity Studies on Tachykinin NK-1 Receptor
  作者：Hubert Josien、Solange Lavielle、Alie Brunissen、Monique Saffroy、Yvette Torrens、Jean-Claude Beaujouan、Jacques Glowinski、Gerard Chassaing

  DOI：10.1021/jm00037a009

  日期：1994.5

  Constrained analogues of phenylalanine have been conceptually designed for analyzing the binding pockets of Phe(7) (S-7) and Phe(8) (S-8), two aromatic residues important for the pharmacological properties of SP, i.e., L-tetrahydroisoquinoleic acid, L-diphenylalanine, L-9-fluorenylglycine (Flg), 2-indanylglycine, the diastereomers of L-1-indanylglycine (Ing) and L-1-benz[f]indanylglycine (Bfi), and the Z and E isomers of dehydrophenylalanine (Delta(z)Phe, Delta(E)Phe). Binding studies were performed with appropriate ligands and tissue preparations allowing the discrimination of the three tachykinin binding sites, NK-1, NK-2, and NK-3. The potencies of these agonists were evaluated in the guinea pig ileum bioassay. According to the binding data, we can conclude that the S-7 subsite is small, only the gauche (-) probe [(2S,3S)-Ing(7)]SP presents a high affinity for specific NK-1 binding sites. Surprisingly, the [Delta(E)Phe(7)]SP analogue, which projects the aromatic ring toward the trans orientation, is over 40-fold more potent than the Z isomer, [Delta(Z)Phe(7)]SP. A plausible explanation of these conflictual results Is that either the binding protein quenches the minor trans rotamer of [(2S,3S)-Ing(7)]SP in solution or this constrained amino acid side chain rotates when inserted in the protein. In position 8, the high binding affinities of [Flg(8)]SP and [(2S,3S)-Bfi(8)]SP suggest that the S-8 subsite is large enough to accept two aromatic rings in the gauche (-) and one aromatic ring in the trans direction. Peptides bearing two conformational probes in positions 7, 8, or 9 led to postulate that S-7, S-8, and S-9 subsites are independent from each other. The volumes available for side chains 7 and 8 can be estimated to be close to 110 and 240 Angstrom(3), respectively. The large volume of the S-8 subsite raises question on the localization of the SP-binding site in the NK-1 receptor. If SP were to bind in the transmembrane domains, the cleft defined by the seven transmembrane segments must rearrange during the binding process in order to bind a peptide in an ac-helical structure and at least one large binding subsite in position 8. Thus, indirect topographical analysis with constrained amino acids might contribute to the analysis of the receptor/ligand dynamics. Finally, this study demonstrates that a good knowledge of the peptidic backbone structure and a combination of constrained amino acids are prerequisites to confidently attribute the preferred orientation(s) of an amino acid side chain.
• Synthesis of enantiomerically pure β,β-diphenylalanine (Dip) and fluorenylglycine (Flg)
  作者：Soledad Royo、Ana I. Jiménez、Carlos Cativiela

  DOI：10.1016/j.tetasy.2006.08.007

  日期：2006.9

  A new strategy for the preparation of both enantiomers of two phenylalanine analogues, beta,beta-diphenylalanine and fluorenylglycine, has been developed. The combination of a high yielding racemic synthesis and a very efficient resolution procedure has provided significant amounts of each amino acid in enantiomerically pure form and suitably protected for use in peptide synthesis. This methodology can be easily applied to the preparation of larger quantities of enantiopure compounds. (c) 2006 Elsevier Ltd. All rights reserved.