5-氰基-DL-色氨酸 | 139393-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 5-氰基-DL-色氨酸
• 中文别名: 5-氰基-L-色氨酸
• 英文名称: 5-cyanotryptophan
• 英文别名: (S)-2-Amino-3-(5-cyano-1H-indol-3-yl)propanoic acid；(2S)-2-amino-3-(5-cyano-1H-indol-3-yl)propanoic acid
• CAS: 139393-02-5
• 化学式: C₁₂H₁₁N₃O₂
• 分子量: 229.238
• InChiKey: RWUVZHFIVNNDBO-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  应存放在2-8°C的环境中，避免光照，并保持在惰性气体中保存。

反应信息

• 作为反应物：
  描述：

  5-氰基-DL-色氨酸 、 1-环己基-2-(3-呋喃)-1H-苯并咪唑-5-羧酸 生成 3-{(S)-2-Carboxy-2-[(1-cyclohexyl-2-furan-3-yl-1H-benzoimidazole-5-carbonyl)-amino]-ethyl}-1H-indole-5-carboxylic acid 、 (2S)-3-(5-carbamoyl-1H-indol-3-yl)-2-[[1-cyclohexyl-2-(3-furyl)benzimidazole-5-carbonyl]amino]propanoic acid
  参考文献：
  名称：

  Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase: discovery of benzimidazole 5-carboxylic amide derivatives with low-nanomolar potency

  摘要：

  Optimization of benzimidazole 5-carboxamide derivatives previously identified as specific inhibitors of the NS5B polymerase of the hepatitis C virus (HCV) has led to the discovery of potent analogues that inhibit the enzyme at low-nanomolar concentrations. Greater than 800-fold improvement in potency from the original lead structure was achieved through the combined effects of conformational rigidification, molecular size extension and the identification of previously unexploited interactions. Furthermore, these inhibitors retain specificity for HCV polymerase relative to other viral and mammalian RNA polymerases. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.12.032
• 作为产物：
  描述：

  1,2-Dimethoxycarbonyl-8-acetyl-1,2,3,3a,8,8a-hexahydropyrrolo<2,3-b>indole 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 溶剂黄146 为溶剂， 生成 5-氰基-DL-色氨酸
  参考文献：
  名称：

  Synthesis of 5-cyano-l-tryptophan

  摘要：

  The 5-bromo derivative 2 of the cyclic tautomer of N(b)-methoxycarbonyl-L-tryptophan methyl ester 1 undergoes reaction with CuCN in refluxing N-methylpyrrolidone (NMP) to give 5-cyano derivative 3a with some ring opened 5-cyano product 3b. Both 3a and 3b can be converted, in high yield, into free 5-cyano-L-tryptophan 4 with BBr3 under mild conditions.

  DOI：

  10.1016/s0040-4039(00)77665-9

文献信息

• [EN] METHODS FOR PRODUCING D-TRYPTOPHAN AND SUBSTITUTED D-TRYPTOPHANS<br/>[FR] PROCÉDÉS DE PRODUCTION DE D-TRYPTOPHANE ET DE D-TRYPTOPHANES SUBSTITUÉS
  申请人：UNIV CALIFORNIA

  公开号：WO2021055696A1

  公开（公告）日：2021-03-25

  Single-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carboxylic acids in both primary and secondary metabolism; and are of great interest due to their biocatalytic potentials. The single-module NRPS IvoA is essential for fungal pigment biosynthesis. As disclosed herein, we show that IvoA catalyzes ATP-dependent unidirectional stereoinversion of L-tryptophan to D-tryptophan with complete conversion. While the stereoinversion is catalyzed by the epimerization (E) domain, the terminal condensation (C) domain stereoselectively hydrolyzes D-tryptophanyl-S-phosphopantetheine thioester and thus represents a noncanonical C domain function. Using IvoA, we demonstrate a biocatalytic stereoinversion/deracemization route to access a variety of substituted D-tryptophan analogs in high enantiomeric excess.

  单模块非核糖体肽合酶（NRPSs）和类NRPS酶在初级和次级代谢中激活和转化羧酸，由于其生物催化潜力，备受关注。单模块NRPS IvoA 对真菌色素生物合成至关重要。正如本文所披露的，我们展示了IvoA 催化ATP依赖的L-色氨酸向D-色氨酸的单向立体反转，实现了完全转化。虽然立体反转由外消旋（E）结构域催化，但末端缩合（C）结构域具有立体选择性地水解D-色氨酰-S-磷酰巯基丝氨酸酯，因此代表了非规范的C结构域功能。利用IvoA，我们展示了一种生物催化的立体反转/去消旋途径，以获得多种取代D-色氨酸类似物，其旋光异构体过量达到高水平。
• Unlocking Reactivity of TrpB: A General Biocatalytic Platform for Synthesis of Tryptophan Analogues
  作者：David K. Romney、Javier Murciano-Calles、Jöri E. Wehrmüller、Frances H. Arnold

  DOI：10.1021/jacs.7b05007

  日期：2017.8.9

  it can form Trp analogues directly from serine (Ser) and the corresponding indole analogue. However, many potentially useful substrates, including bulky or electron-deficient indoles, are poorly accepted. We have applied directed evolution to TrpB from Pyrococcus furiosus and Thermotoga maritima to generate a suite of catalysts for the synthesis of previously intractable Trp analogues. For the most challenging

  氨基酸色氨酸（Trp）的衍生物用作具有广泛生物学特性的复杂分子的化学和生物合成的前体。Trp类似物也可作为药物化学的基础材料和化学生物学的工具。虽然Trp类似物的对映选择性合成通常很长并且需要使用保护基，但是酶具有以更少的步骤合成原始产物的潜力，并且具有原始的化学和立体选择性，这是生物催化的特征。TrpB酶特别吸引人，因为它可以直接从丝氨酸（Ser）和相应的吲哚类似物形成Trp类似物。然而，许多潜在有用的底物，包括大体积的或缺乏电子的吲哚，都被人们接受。我们已经从激烈热球菌（Pyrococcus furiosus）和马氏热球菌（Thermotoga maritima）产生了一系列催化剂，用于合成以前难以处理的Trp类似物。对于最具挑战性的底物，例如硝基吲哚，提高活性的关键在于普遍保守且具有重要机械意义的残基E104的突变。新催化剂高水平表达（> 200 mg / L大肠杆菌培养），并可以通
• A Panel of TrpB Biocatalysts Derived from Tryptophan Synthase through the Transfer of Mutations that Mimic Allosteric Activation
  作者：Javier Murciano-Calles、David K. Romney、Sabine Brinkmann-Chen、Andrew R. Buller、Frances H. Arnold

  DOI：10.1002/anie.201606242

  日期：2016.9.12

  Naturally occurring enzyme homologues often display highly divergent activity with non‐natural substrates. Exploiting this diversity with enzymes engineered for new or altered function, however, is laborious because the engineering must be replicated for each homologue. A small set of mutations of the tryptophan synthase β‐subunit (TrpB) from Pyrococcus furiosus, which mimics the activation afforded

  天然存在的酶同系物通常表现出与非天然底物高度不同的活性。然而，用经过改造的酶来开发新功能或改变其功能的多样性是很费力的，因为必须为每个同源物重复进行改造。激烈热球菌色氨酸合酶β亚基（TrpB）的一小部分突变模仿α-亚基结合提供的激活，被证明在不同的TrpB同源物中具有相似的激活作用，序列同一性低至57％。动力学和光谱分析表明，突变通过相同的机制起作用：模仿α-亚基结合。从这些酶中，我们确定了一种新的TrpB催化剂，该催化剂在5取代色氨酸的合成中显示出非常广泛的活性。这证明了变构活化可以在整个蛋白质家族中概括，以探索天然序列多样性以进行所需的生物催化转化。
• Complete Stereoinversion of <scp>l</scp>-Tryptophan by a Fungal Single-Module Nonribosomal Peptide Synthetase
  作者：Yang Hai、Matthew Jenner、Yi Tang

  DOI：10.1021/jacs.9b08898

  日期：2019.10.16

  Single-module nonribosomal peptide synthetases (NRPSs) and NRPS-like enzymes activate and transform carboxylic acids in both primary and secondary metabolism and are of great interest due to their biocatalytic potentials. The single-module NRPS IvoA is essential for fungal pigment biosynthesis. Here, we show that IvoA catalyzes ATP-dependent unidirectional stereo inversion of L-tryptophan to D-tryptophan with complete conversion. While the stereoinversion is catalyzed by the epimerization (E) domain, the terminal condensation (C) domain stereoselectively hydrolyzes D-tryptophanyl-S-phosphopantetheine thioester and thus represents a noncanonical C domain function. Using IvoA, we demonstrate a biocatalytic stereoinversion/deracemization route to access a variety of substituted D-tryptophan analogs in high enantiomeric excess.
• Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase: discovery of benzimidazole 5-carboxylic amide derivatives with low-nanomolar potency
  作者：Pierre L Beaulieu、Michael Bös、Yves Bousquet、Patrick DeRoy、Gulrez Fazal、Jean Gauthier、James Gillard、Sylvie Goulet、Ginette McKercher、Marc-André Poupart、Serge Valois、George Kukolj

  DOI：10.1016/j.bmcl.2003.12.032

  日期：2004.2

  Optimization of benzimidazole 5-carboxamide derivatives previously identified as specific inhibitors of the NS5B polymerase of the hepatitis C virus (HCV) has led to the discovery of potent analogues that inhibit the enzyme at low-nanomolar concentrations. Greater than 800-fold improvement in potency from the original lead structure was achieved through the combined effects of conformational rigidification, molecular size extension and the identification of previously unexploited interactions. Furthermore, these inhibitors retain specificity for HCV polymerase relative to other viral and mammalian RNA polymerases. (C) 2003 Elsevier Ltd. All rights reserved.