4-fluorotryptophan

• 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
• 英文名称: 4-fluorotryptophan
• 英文别名: L-4-fluorotryptophan；(2S)-2-azaniumyl-3-(4-fluoro-1H-indol-3-yl)propanoate
• 化学式: C₁₁H₁₁FN₂O₂
• 分子量: 222.219
• InChiKey: DEBQMEYEKKWIKC-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  79.1
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-fluorotryptophan 在 氯化亚砜 、 sulfur 作用下， 以 xylene 为溶剂， 反应 34.0h， 生成
  参考文献：
  名称：

  [EN] COMPOUNDS FOR TREATMENT OF METABOLIC SYNDROME
  [FR] COMPOSÉS POUR LE TRAITEMENT DU SYNDROME MÉTABOLIQUE

  摘要：

  本发明涉及公式I或II的新化合物，其合成以及在治疗代谢综合征中的应用，特别是用于治疗I型或II型糖尿病和/或代谢综合征或代谢疾病或代谢紊乱。

  公开号：

  WO2012130912A1
• 作为产物：
  描述：

  4-氟吲哚 在 盐酸 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 sodium hydride 、 三苯基膦 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 4.92h， 生成 4-fluorotryptophan
  参考文献：
  名称：

  Synthesis of (L)-4-Fluorotryptophan

  摘要：

  A new synthesis of stereochemically pure (L)-4-fluorotryptophan [i.e., (2S)-4-fluorotryptophan]in seven steps from 4-fluoroindole is described. A key reaction in the synthetic strategy is a diastereoselective alkylation of the Schollkopf chiral auxiliary with a fluorinated electrophile. All reaction steps are efficient and proceed in at least 80% yield.

  DOI：

  10.1080/00397911.2010.523154

文献信息

• Facile in Vitro Biocatalytic Production of Diverse Tryptamines
  作者：Allwin D. McDonald、Lydia J. Perkins、Andrew R. Buller

  DOI：10.1002/cbic.201900069

  日期：2019.8

  the product line: Tryptamines are important synthons in bioactive natural products, but general synthetic routes to tryptamine analogues are limited. We present a highly active and promiscuous biosynthetic cascade using an engineered tryptophan synthase (TrpB) and native tryptophan decarboxylase (TDC) capable of producing a diverse set of tryptamines from readily accessible indoles.

  产品线多样化：色胺是生物活性天然产物中的重要合成子，但色胺类似物的一般合成路线有限。我们提出了一种高度活跃且混杂的生物合成级联，使用工程色氨酸合酶（TrpB）和天然色氨酸脱羧酶（TDC），能够从容易获得的吲哚中产生多种色胺。
• [EN] RAS BINDING PEPTIDES AND METHODS OF USE<br/>[FR] PEPTIDES DE LIAISON À RAS ET MÉTHODES D'UTILISATION
  申请人：RA PHARMACEUTICALS INC

  公开号：WO2017181061A1

  公开（公告）日：2017-10-19

  The present invention provides Ras modulators including inhibitors and/or antagonists of Ras, Ras binding, and Ras-dependent cell signaling activity. Also provided are methods of utilizing the Ras modulators as therapeutics.

  本发明提供了Ras调节剂，包括Ras的抑制剂和/或拮抗剂，以及Ras结合和Ras依赖的细胞信号活性。还提供了利用这些Ras调节剂作为治疗药物的方法。
• Biocatalysts from cyanobacterial hapalindole pathway afford antivirulent isonitriles against MRSA
  作者：Brittney M Bunn、Mizhi Xu、Chase M Webb、Rajesh Viswanathan

  DOI：10.1007/s12038-021-00156-4

  日期：2021.6

  The emergence of resistance to frontline antibiotics has called for novel strategies to combat serious pathogenic infections. Methicillin-resistant Staphylococcus aureus [MRSA] is one such pathogen. As opposed to traditional antibiotics, bacteriostatic anti-virulent agents disarm MRSA, without exerting pressure, that cause resistance. Herein, we employed a thermophilic Thermotoga maritima tryptophan synthase (TmTrpB1) enzyme followed by an isonitrile synthase and Fe(II)-α-ketoglutarate-dependent oxygenase, in sequence as biocatalysts to produce antivirulent indole vinyl isonitriles. We report on conversion of simple derivatives of indoles to their C3-vinyl isonitriles, as the enzymes employed here demonstrated broader substrate tolerance. In toto, eight distinct L-Tryptophan derived α-amino acids (7) were converted to their bioactive vinyl isonitriles (3) by action of an isonitrile synthase (WelI1) and an Fe(II)-α-ketoglutarate-dependent oxygenase (WelI3) yielding structural variants possessing antivirulence against MRSA. These indole vinyl isonitriles at 10 μg/mL are effective as antivirulent compounds against MRSA, as evidenced through analysis of rabbit blood hemolysis assay. Based on a homology modelling exercise, of enzyme-substrate complexes, we deduced potential three dimensional alignments of active sites and glean mechanistic insights into the substrate tolerance of the Fe(II)-α-ketoglutarate-dependent oxygenase.

  一线抗生素耐药性的出现，要求我们采取新的策略来应对严重的病原体感染。耐甲氧西林金黄色葡萄球菌（MRSA）就是这样一种病原体。与传统抗生素相比，抑菌性抗病毒制剂能解除 MRSA 的威胁，而不会对其造成压力，导致其产生耐药性。在此，我们采用了嗜热的海洋嗜热菌（Thermotoga maritima）色氨酸合成酶（TmTrpB1）、异腈合成酶和依赖于Fe(II)-α-酮戊二酸的加氧酶作为生物催化剂，依次生成抗病毒的吲哚乙烯基异腈。我们报告了将吲哚的简单衍生物转化为其 C3-乙烯基异腈的情况，因为这里使用的酶具有更广泛的底物耐受性。在异腈合成酶（WelI1）和依赖于Fe（II）-α-酮戊二酸的加氧酶（WelI3）的作用下，总共有八种不同的L-色氨酸衍生的α-氨基酸（7）被转化为具有生物活性的乙烯基异腈（3），产生的结构变体对MRSA具有抗病毒作用。这些吲哚乙烯基异腈类化合物在 10 μg/mL 的浓度下可作为抗 MRSA 的有效抗病毒化合物，兔血液溶血试验分析证明了这一点。基于酶-底物复合物的同源建模工作，我们推导出了活性位点的潜在三维排列，并从机理上深入了解了依赖铁（II）-α-酮戊二酸的加氧酶对底物的耐受性。
• Promiscuous indolyl vinyl isonitrile synthases in the biogenesis and diversification of hapalindole-type alkaloids
  作者：Kuljira Ittiamornkul、Qin Zhu、Danai S. Gkotsi、Duncan R. M. Smith、Matthew L. Hillwig、Nicole Nightingale、Rebecca J. M. Goss、Xinyu Liu

  DOI：10.1039/c5sc02919h

  日期：——

  Promiscuous cis-indolyl vinyl isonitrile biosynthetic pathway allowed the preparatively useful generation of nine halosubstituted antibiotic analogues with increased lipophilicity.

  杂交的顺式吲哚基乙烯异腈生物合成途径允许制备有用的生成了九种卤代抗生素类似物，其脂溶性增加。
• Directed evolution of the tryptophan synthase β-subunit for stand-alone function recapitulates allosteric activation
  作者：Andrew R. Buller、Sabine Brinkmann-Chen、David K. Romney、Michael Herger、Javier Murciano-Calles、Frances H. Arnold

  DOI：10.1073/pnas.1516401112

  日期：2015.11.24

  Many enzymes perform desirable biochemical transformations, but are not suitable to use as biocatalysts outside of the cell. In particular, enzymes from heteromeric complexes typically have decreased activity when removed from their protein partners. We used directed evolution to restore the catalytic efficiency of the tryptophan synthase β-subunit (TrpB), which synthesizes l -tryptophan from l -serine and indole, surpassing the activity of the native complex. Experiments show that activating mutations promote catalysis through the same mechanism as partner protein binding, establishing that isolated subunits may be readily reactivated through directed evolution. Engineering TrpB for stand-alone function restored high activity with indole analogs, providing a simplified enzyme platform for the biocatalytic production of noncanonical amino acids.

  标题：重要性 许多酶执行令人满意的生化转化，但通常不适合在细胞外作为生物催化剂使用。特别是，异源复合物中的酶通常在与其蛋白质伙伴分离后活性降低。我们利用定向进化恢复色氨酸合成酶β亚基（TrpB）的催化效率，该亚基从丝氨酸和吲哚合成l-色氨酸，超越了天然复合物的活性。实验证明，激活突变通过与伙伴蛋白结合相同的机制促进催化，表明隔离的亚基可以通过定向进化轻松重新激活。将TrpB工程化为独立功能可恢复与吲哚类似物的高活性，为非规范氨基酸的生物催化生产提供了简化的酶平台。