(2S,3S)-N-[(9-fluorenylmethoxy)carbonyl]-3-methylphenylalanine | 247175-69-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (2S,3S)-N-[(9-fluorenylmethoxy)carbonyl]-3-methylphenylalanine
• 英文别名: N-Fmoc-(2S,3S)-β-methylphenylalanine；N-(9-fluorenylmethoxycarbonyl)-(2S,3S)-erythro-L-β-methylphenylalanine；(2S,3S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-phenylbutanoic acid
• CAS: 247175-69-5
• 化学式: C₂₅H₂₃NO₄
• 分子量: 401.462
• InChiKey: ZQWJZRLWGALBIQ-HJPURHCSSA-N

物化性质

• 沸点：
  616.2±50.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S)-N-[(9-fluorenylmethoxy)carbonyl]-3-methylphenylalanine 在 哌啶 、 4-吡咯烷基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 生成 methyl (8R,9S,2'S,3'S,2E,4Z,6E)-8-[2'-amino-3'-phenylbutanoyloxy]-9,10-epoxy-9-methyl-2,4,6-decatrienoate
  参考文献：
  名称：

  t标记的AK毒素I的甲基酯的合成，这是一种由Alternaria alternata日本梨病原体产生的宿主特异性毒素。

  摘要：

  AK-毒素I是日本梨（Pyrus serotina）的一种宿主特异性毒素，是由其三个前体片段（共轭二烯-羧酸，手性环氧醇和β-甲基苯基丙氨酸）合成的甲酯形式的。环氧醇片段衍生自D-果糖，其中通过使用1-重氮-2-氧代丙基膦酸二甲酯使半缩醛碳有效同化为炔烃是关键反应。通过重复的Wittig反应制备二烯-羧酸片段，并通过Stille反应将其与环氧醇片段结合。用立体化学纯的β-甲基苯基丙氨酸片段酯化合并的产物，得到目标化合物。该方法用于制备tri标记的AK毒素I的甲酯，其比放射性为213 GBq / mmol。

  DOI：

  10.1271/bbb.63.1253
• 作为产物：
  描述：

  (2S,3S)-methylphenylalanine 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以60%的产率得到(2S,3S)-N-[(9-fluorenylmethoxy)carbonyl]-3-methylphenylalanine
  参考文献：
  名称：

  Use of .beta.-Methylphenylalanine (.beta.MeF) Residues To Probe the Nature of the Interaction of Substance P with Its Receptor: Effects of .beta.MeF-Containing Substance P Analogs on Rabbit Iris Smooth Muscle Contraction

  摘要：

  The effects of substituting (2S,3S)-beta-methylphenylalanine (S-beta MeF) or (2S,3R)-beta-methylphenylalanine (R-beta MeF) for the Phe(7) and/or Phe(8) residues of the tachykinin substance P (SP, RPKPQQFFGLM-NH2) upon the ability of SP to stimulate contraction of the rabbit iris smooth muscle were investigated. The eight beta MeF-containing SP analogs (four monosubstituted analogs, four disubstituted analogs) 1-8 were synthesized and found to be agonists of SP in the smooth muscle contraction assay, having EC(50) values ranging from 0.15 to 10.0 nM. Three analogs are significantly more active than SP [8R-(beta MeF)SP (4), 7S,8S-(beta MeF)(2)SP (5), and 7R,8S-(beta MeF)(2)SP (6)], three analogs are approximately equipotent with SP [7S-(beta MeF)SP (1), 7R-(beta MeF)SP (2), and 7S,8R-(beta MeF)(2)SP (8)], and two analogs are significantly less active than SP [8S-(beta MeF)SP (3) and 7R,8R-(beta MeF)(2)SP (7)]. The effects of the beta MeF substitutions upon the activity of SP are not additive and cannot be explained using simple conformational models which focus only on the side chain conformations of the beta MeF residues. It is postulated that the beta MeF residues induce minor distortions in the peptide backbone with resultant consequences upon peptide-receptor binding which are not dictated solely by the side chain conformations. This idea is consistent with H-1-NMR data for the monosubstituted analogs 1-4, which imply that the beta MeF substitutions cause slight distortions in the peptide backbone and that the beta MeF side chains are assuming trans or gauche(-) conformations.

  DOI：

  10.1021/jm00013a024

文献信息

• Asymmetric total synthesis of AK-toxins
  作者：Ippei Uemura、Hisashi Miyagawa、Tamio Ueno

  DOI：10.1016/s0040-4020(02)00117-5

  日期：2002.3

  A practical total synthesis of AK-toxins (AK-toxin I, 1; II, 2), host-specific toxins against the Japanese pear, has been achieved in 10% total yield, starting from the key intermediate 6. The (2E,4Z,6E)-conjugated triene system was successfully constructed by the use of the Stille coupling reaction between the (E,Z)-bromodiene (17) and (E)-stannylacrylate (21). The (E,Z)-configuration of 17 was established with excellent geometrical purity by palladium-catalyzed stereoselective hydrogenolysis of gem-dibromide (15), which was derived from 6 via the Wittig-Horner reactions. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Constrained H-Phe-Phe-NH₂ Analogues with High Affinity to the Substance P 1–7 Binding Site and with Improved Metabolic Stability and Cell Permeability
  作者：Rebecca Fransson、Christian Sköld、Jadel M. Kratz、Richard Svensson、Per Artursson、Fred Nyberg、Mathias Hallberg、Anja Sandström

  DOI：10.1021/jm400209h

  日期：2013.6.27

  We recently reported the discovery, of H-Phe-Phe-NH2 as a small and high affinity ligand for the substance P 1-7 (SP1-7, H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH) specific binding site and its intriguing ability to reduce neuropathic pain. With the overall aim to develop stable and orally bioavailable SP1-7 mimetics, the dipeptide was chosen as a lead compound. Herein the structure activity relationship (SAR) of a set of modified H-Phe-Phe-NH2 analogues is presented together with their potential active uptake by PEPT1 transporter, intestinal permeability, and metabolic stability. Local constraints via peptide backbone methylation or preparation of cyclized analogues based on pyrrolidine were evaluated and were shown to significantly improve the in vitro pharmacokinetic properties. The SAR was rationalized by deriving a plausible binding pose for the high affinity ligands. Rigidification using a 3-phenylpyrrolidine moiety in the C-terminal of H-Phe-Phe-NH2 resulted in high affinity and improved intrinsic clearance and intestinal epithelial permeability.
• Synthesis of the Methyl Ester of Tritium-labeled AK-toxin I, a Host-specific Toxin Produced by<i>Alternaria alternata</i>Japanese Pear Pathotype
  作者：Masakazu OKADA、Hisashi MIYAGAWA、Tamio UENO

  DOI：10.1271/bbb.63.1253

  日期：1999.1

  AK-toxin I, a host-specific toxin to Japanese pear (Pyrus serotina), was synthesized as its methyl ester from three precursor fragments: conjugated diene-carboxylic acid, chiral epoxyalcohol and β-methylphenylalanine. The epoxyalcohol fragment was derived from D-fructose, in which effective homologation of the hemiacetal carbon to alkyne by using dimethyl 1-diazo-2-oxopropylphosphonate was the key

  AK-毒素I是日本梨（Pyrus serotina）的一种宿主特异性毒素，是由其三个前体片段（共轭二烯-羧酸，手性环氧醇和β-甲基苯基丙氨酸）合成的甲酯形式的。环氧醇片段衍生自D-果糖，其中通过使用1-重氮-2-氧代丙基膦酸二甲酯使半缩醛碳有效同化为炔烃是关键反应。通过重复的Wittig反应制备二烯-羧酸片段，并通过Stille反应将其与环氧醇片段结合。用立体化学纯的β-甲基苯基丙氨酸片段酯化合并的产物，得到目标化合物。该方法用于制备tri标记的AK毒素I的甲酯，其比放射性为213 GBq / mmol。
• Use of .beta.-Methylphenylalanine (.beta.MeF) Residues To Probe the Nature of the Interaction of Substance P with Its Receptor: Effects of .beta.MeF-Containing Substance P Analogs on Rabbit Iris Smooth Muscle Contraction
  作者：David M. Birney、Derek C. Cole、Craig E. Crosson、Brenda F. Kahl、Bart W. Neff、Ted W. Reid、Kaijun Ren、Robert D. Walkup

  DOI：10.1021/jm00013a024

  日期：1995.6

  The effects of substituting (2S,3S)-beta-methylphenylalanine (S-beta MeF) or (2S,3R)-beta-methylphenylalanine (R-beta MeF) for the Phe(7) and/or Phe(8) residues of the tachykinin substance P (SP, RPKPQQFFGLM-NH2) upon the ability of SP to stimulate contraction of the rabbit iris smooth muscle were investigated. The eight beta MeF-containing SP analogs (four monosubstituted analogs, four disubstituted analogs) 1-8 were synthesized and found to be agonists of SP in the smooth muscle contraction assay, having EC(50) values ranging from 0.15 to 10.0 nM. Three analogs are significantly more active than SP [8R-(beta MeF)SP (4), 7S,8S-(beta MeF)(2)SP (5), and 7R,8S-(beta MeF)(2)SP (6)], three analogs are approximately equipotent with SP [7S-(beta MeF)SP (1), 7R-(beta MeF)SP (2), and 7S,8R-(beta MeF)(2)SP (8)], and two analogs are significantly less active than SP [8S-(beta MeF)SP (3) and 7R,8R-(beta MeF)(2)SP (7)]. The effects of the beta MeF substitutions upon the activity of SP are not additive and cannot be explained using simple conformational models which focus only on the side chain conformations of the beta MeF residues. It is postulated that the beta MeF residues induce minor distortions in the peptide backbone with resultant consequences upon peptide-receptor binding which are not dictated solely by the side chain conformations. This idea is consistent with H-1-NMR data for the monosubstituted analogs 1-4, which imply that the beta MeF substitutions cause slight distortions in the peptide backbone and that the beta MeF side chains are assuming trans or gauche(-) conformations.