(2S,3R)-1-((fluoren-9-ylmethyl)oxycarbonyl)-3-(4-((bis-(tert-butyl)phosphono)methyl)phenyl)piperidine-2-carboxylic acid | 510773-78-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,3R)-1-((fluoren-9-ylmethyl)oxycarbonyl)-3-(4-((bis-(tert-butyl)phosphono)methyl)phenyl)piperidine-2-carboxylic acid
• 英文别名: (2S,3R)-3-[4-[bis[(2-methylpropan-2-yl)oxy]phosphorylmethyl]phenyl]-1-(9H-fluoren-9-ylmethoxycarbonyl)piperidine-2-carboxylic acid
• CAS: 510773-78-1
• 化学式: C₃₆H₄₄NO₇P
• 分子量: 633.722
• InChiKey: QKYVRJAWMGJSLS-DICHSLLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3R)-1-((fluoren-9-ylmethyl)oxycarbonyl)-3-(4-((bis-(tert-butyl)phosphono)methyl)phenyl)piperidine-2-carboxylic acid 在 哌啶 、 三乙基硅烷 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.0h， 生成 2-[(2S,3R)-2-[[1-[[(2S)-4-amino-1-(3-naphthalen-1-ylpropylamino)-1,4-dioxobutan-2-yl]carbamoyl]cyclohexyl]carbamoyl]-3-[4-(phosphonomethyl)phenyl]piperidin-1-yl]-2-oxoacetic acid
  参考文献：
  名称：

  Synthesis of N -Fmoc 3-(4-(di-( tert -butyl)phosphonomethyl)phenyl)pipecolic acid as a conformationally constrained phosphotyrosyl mimetic suitably protected for peptide synthesis

  摘要：

  Phosphonomethylphenylalanine (Pmp, 2) has shown wide utility as a hydrolytically stable phosphtyrosyl (pTyr, 1) mimetic, particularly in Src homology 2 (SH2) domain-binding peptides. (2S,3R)-3-(4-(phosphonomethyl)phenyl)pipecolic acid (3) represents a variant of Pmp having phi and chi(1) torsion angles constrained through incorporation into the piperidinyl ring structure contained within pipecolic acid. Reported herein is the enantioselective preparation of 3, in an orthogonally protected form (4) suitable for use in peptide synthesis. Stereochemistries at both the 2- and 3-positions are derived inductively from a single chiral center provided by the commercially available Evans chiral auxiliary, (4S)-4-benzyl-1,3-oxazolidin-2-one. Incorporation of 4 into a Grb2 SH2 domain-directed tripeptide (18) showed that Grb2 SH2 domain-binding affinity was reduced relative to the parent Pmp-containing tripeptide (19). Although conformational constraint did not enhance affinity in this case, novel amino acid analogue 4 may serve as a useful tool for the induction of defined phosphotyrosyl geometry in peptides directed at other signal transduction targets. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)01421-7
• 作为产物：
  描述：

  methyl (2S,3R)-3-(4-((bis-(tert-butyl)phosphono)methyl)phenyl)piperidine-2-carboxylate 在 sodium hydroxide 、 甲基安非他命 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 生成 (2S,3R)-1-((fluoren-9-ylmethyl)oxycarbonyl)-3-(4-((bis-(tert-butyl)phosphono)methyl)phenyl)piperidine-2-carboxylic acid
  参考文献：
  名称：

  Synthesis of N -Fmoc 3-(4-(di-( tert -butyl)phosphonomethyl)phenyl)pipecolic acid as a conformationally constrained phosphotyrosyl mimetic suitably protected for peptide synthesis

  摘要：

  Phosphonomethylphenylalanine (Pmp, 2) has shown wide utility as a hydrolytically stable phosphtyrosyl (pTyr, 1) mimetic, particularly in Src homology 2 (SH2) domain-binding peptides. (2S,3R)-3-(4-(phosphonomethyl)phenyl)pipecolic acid (3) represents a variant of Pmp having phi and chi(1) torsion angles constrained through incorporation into the piperidinyl ring structure contained within pipecolic acid. Reported herein is the enantioselective preparation of 3, in an orthogonally protected form (4) suitable for use in peptide synthesis. Stereochemistries at both the 2- and 3-positions are derived inductively from a single chiral center provided by the commercially available Evans chiral auxiliary, (4S)-4-benzyl-1,3-oxazolidin-2-one. Incorporation of 4 into a Grb2 SH2 domain-directed tripeptide (18) showed that Grb2 SH2 domain-binding affinity was reduced relative to the parent Pmp-containing tripeptide (19). Although conformational constraint did not enhance affinity in this case, novel amino acid analogue 4 may serve as a useful tool for the induction of defined phosphotyrosyl geometry in peptides directed at other signal transduction targets. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)01421-7