N-(4-methoxybenzyl)-L-phenylalanine | 161563-31-1

• 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: N-(4-methoxybenzyl)-L-phenylalanine
• 英文别名: (S)-2-((4-methoxybenzyl)ammonio)-3-phenylpropanoate；PMB-Phe-OH；(S)-2-((4-Methoxybenzyl)amino)-3-phenylpropanoic acid；(2S)-2-[(4-methoxyphenyl)methylamino]-3-phenylpropanoic acid
• CAS: 161563-31-1
• 化学式: C₁₇H₁₉NO₃
• 分子量: 285.343
• InChiKey: KXZJVJXEKVDDDZ-INIZCTEOSA-N

物化性质

• 沸点：
  453.7±40.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-methoxybenzyl)-L-phenylalanine 在 甲酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 甲苯 、 仲丁醇 为溶剂， 反应 2.0h， 生成 (3S,8aS)-2-(4-methoxybenzyl)-3-benzylhexahydropyrrolo[1,2a]pyrazine-1,4-dione
  参考文献：
  名称：

  合成衍生自二酮哌嗪的复杂桥连生物碱：阳离子级联方法对步石酸，对乙酰氨基苯甲酰胺和相关系统的影响

  摘要：

  区域选择性烯醇盐的形成，然后对不对称脯氨酸衍生的二酮哌嗪（DKPs）进行立体选择性亲电淬灭，使得能够合成各种取代的DKP，包括可以进一步被取代和环化的一种底物，从而形成双环[2.2.2]二氮杂辛烷核心结构天然产品中的对乙酰氨基苯甲酸酯和十八烷酸中存在。

  DOI：

  10.1016/j.tetlet.2006.09.046
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 sodium tetrahydroborate 、 sodium hydroxide 作用下， 反应 1.0h， 生成 N-(4-methoxybenzyl)-L-phenylalanine
  参考文献：
  名称：

  The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1

  摘要：

  The rationale for targeting the human di-/tripeptide transporter hPEPT1 for oral drug delivery has been well established by several drug and prodrug cases. The aim of this study was to synthesize novel ketomethylene modified tripeptidomimetics and to investigate their binding affinity for hPEPT1. Three related tripeptidomimetics of the structure H-Phe-psi[COCH2]-Ser(Bz)-X-aa-OH were synthesized applying the tandem chain extension aldol reaction, where amino acid derived beta-keto imides were stereoselectively converted to alpha-substituted gamma-keto imides. In addition, three corresponding tripeptides, composed of amide bonds, were synthesized for comparison of binding affinities. The six investigated compounds were all defined as high affinity ligands (K-i-values < 0.5 mM) for hPEPT1 by measuring the concentration dependent inhibition of apical [C-14]Gly-Sar uptake in Caco-2 cells. Consequently, the ketomethylene replacement for the natural amide bond and alpha-side chain modifications appears to offer a promising strategy to modify tripeptidic structures while maintaining a high affinity for hPEPT1. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.108

文献信息

• Studies towards complex bridged alkaloids: regio- and stereocontrolled enolate chemistry of 2,5-diketopiperazines
  作者：Mark Pichowicz、Nigel S. Simpkins、Alexander J. Blake、Claire Wilson

  DOI：10.1016/j.tet.2008.02.020

  日期：2008.4

  N-protected diketopiperazines (DKPs) via enolate intermediates has been studied. The enolate reactions were highly diastereocontrolled, leading to enantiopure DKP products if chiral amino acid precursors were employed, and giving racemic products, starting with centrosymmetric DKPs, even when a chiral lithium amide base was used to generate the lithium enolate. With unsymmetrical DKPs derived from proline

  已经研究了通过烯醇化物中间体取代对称的N-保护的二酮哌嗪（DKP）。烯醇盐的反应是高度非对映体控制的，如果使用手性氨基酸前体，则会产生对映体纯的DKP产物，即使使用手性锂酰胺碱生成烯醇酸锂，也可以从中心对称的DKPs开始生成外消旋产物。对于衍生自脯氨酸和丙氨酸，苯丙氨酸或缬氨酸的不对称DKP，烯醇取代发生在脯氨酸残基上，具有很高的区域选择性和立体选择性。这样就可以合成取代的DKP，该化合物可以通过阳离子过程环化，得到天然产物对乙酰氨基酚和Stephacid中存在的双环[2.2.2]二氮杂辛烷核心结构。
• Development of Reduced Peptide Bond Pseudopeptide Michael Acceptors for the Treatment of Human African Trypanosomiasis
  作者：Santo Previti、Roberta Ettari、Carla Di Chio、Rahul Ravichandran、Marta Bogacz、Ute A. Hellmich、Tanja Schirmeister、Sandro Cosconati、Maria Zappalà

  DOI：10.3390/molecules27123765

  日期：——

  micro/sub-micromolar activity towards the protozoa. However, whilst impressive binding affinity against rhodesain has been observed, the limited selectivity towards the target still remains a hard challenge for the development of antitrypanosomal agents. In this paper, we report the synthesis, biological evaluation, as well as docking studies of a series of reduced peptide bond pseudopeptide Michael acceptors

  非洲人类锥虫病 (HAT) 是一种在撒哈拉以南地区广泛传播的地方性原生动物疾病，由锥虫引起。冈比亚和T. b.罗德西亚。针对罗得赛因（ T. b.的主要半胱氨酸蛋白酶）的分子的开发。 rhodesense已开发出一组对原生动物具有微/亚微摩尔活性的抑制剂。然而，虽然已经观察到对罗得西亚的令人印象深刻的结合亲和力，但对靶标的有限选择性仍然是抗锥虫药物开发的严峻挑战。在本文中，我们报告了一系列作为潜在抗 HAT 药物的还原肽键伪肽 Michael 受体 ( SPR10 – SPR19 ) 的合成、生物学评价以及对接研究。新分子显示出针对罗得赛的低微摩尔/亚微摩尔范围内的K值，以及 1314 至 6950 M −1 min −1之间的k 2nd值。除少数例外，观察到对人组织蛋白酶 L 具有明显的选择性。针对T. b 的体外测定。在brucei培养物中， SPR16和SPR18对原生动物表现出个位
• Synthesis of biosynthetic precursors of chromophores of red fluorescent proteins
  作者：P. E. Ivashkin、K. A. Lukyanov、I. V. Yampolsky

  DOI：10.1134/s1068162011040066

  日期：2011.7

  A method for the synthesis of 5-arylidene-3,5-dihydro-4H-imidazol-4-ones corresponding to the chromophore of the green fluorescent protein ( GFP) with acylaminoalkyl substituents at position 2 of the imidazolone core has been developed. These biomimetic model compounds are the precursors of the chromophores of red fluorescent proteins. The method is based on the masking of the dehydrotyrosine fragment of target compounds by the beta-hydroxytyrosine moiety. The key stages of the synthesis include the condensation of beta-hydroxytyrosine with the appropriate N-acetylamino acid, the unmasking of dehydrotyrosine by O-acylation with subsequent elimination, and the cyclization of the resulting 3-acylaminocinnamic acid derivatives in basic medium.
• The tandem chain extension aldol reaction used for synthesis of ketomethylene tripeptidomimetics targeting hPEPT1
  作者：Karina Thorn、Carsten Uhd Nielsen、Palle Jakobsen、Bente Steffansen、Charles K. Zercher、Mikael Begtrup

  DOI：10.1016/j.bmcl.2011.05.108

  日期：2011.8

  The rationale for targeting the human di-/tripeptide transporter hPEPT1 for oral drug delivery has been well established by several drug and prodrug cases. The aim of this study was to synthesize novel ketomethylene modified tripeptidomimetics and to investigate their binding affinity for hPEPT1. Three related tripeptidomimetics of the structure H-Phe-psi[COCH2]-Ser(Bz)-X-aa-OH were synthesized applying the tandem chain extension aldol reaction, where amino acid derived beta-keto imides were stereoselectively converted to alpha-substituted gamma-keto imides. In addition, three corresponding tripeptides, composed of amide bonds, were synthesized for comparison of binding affinities. The six investigated compounds were all defined as high affinity ligands (K-i-values < 0.5 mM) for hPEPT1 by measuring the concentration dependent inhibition of apical [C-14]Gly-Sar uptake in Caco-2 cells. Consequently, the ketomethylene replacement for the natural amide bond and alpha-side chain modifications appears to offer a promising strategy to modify tripeptidic structures while maintaining a high affinity for hPEPT1. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis towards complex bridged alkaloids derived from diketopiperazines: a cationic cascade approach to stephacidins, paraherquamides and related systems
  作者：Mark Pichowicz、Nigel S. Simpkins、Alexander J. Blake、Claire Wilson

  DOI：10.1016/j.tetlet.2006.09.046

  日期：2006.11

  Regioselective enolate formation, followed by stereoselective electrophilic quenching of unsymmetrical proline-derived diketopiperazines (DKPs), enabled the synthesis of variously substituted DKPs, including one substrate which could be further substituted and cyclised to give the bicyclo[2.2.2]diazaoctane core structure present in paraherquamide and stephacidin natural products.

  区域选择性烯醇盐的形成，然后对不对称脯氨酸衍生的二酮哌嗪（DKPs）进行立体选择性亲电淬灭，使得能够合成各种取代的DKP，包括可以进一步被取代和环化的一种底物，从而形成双环[2.2.2]二氮杂辛烷核心结构天然产品中的对乙酰氨基苯甲酸酯和十八烷酸中存在。