(2S,4R)-5-hydroxyleucine | 118758-45-5

• 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: (2S,4R)-5-hydroxyleucine
• 英文别名: 5-Hydroxyleucine；(2S,4R)-2-azaniumyl-5-hydroxy-4-methylpentanoate
• CAS: 118758-45-5
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: SDCAQJCTUOFAKD-UHNVWZDZSA-N

物化性质

• 沸点：
  297.5±35.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,4R)-5-hydroxyleucine 在 聚甘氨酸 NosE gene from Escherichia coli 、 β-烟酰胺腺嘌呤二核苷酸 、 铬酸 、 zinc(II) sulfate 作用下， 以 盐酸 、 水 为溶剂， 反应 6.25h， 生成 (4S)-4-甲基-l-脯氨酸
  参考文献：
  名称：

  Biosynthesis of 4-Methylproline in Cyanobacteria:  Cloning of nosE and nosF Genes and Biochemical Characterization of the Encoded Dehydrogenase and Reductase Activities

  摘要：

  The biosynthesis of the unusual amino acid 4-methylproline in the Nostoc genus of cyanobacteria was investigated on the genetic and enzymatic level. Two genes involved in the biosynthesis were cloned and the corresponding enzymes, a zinc-dependent long-chain dehydrogenase and a Delta(1)-pyrroline-5-carboxylic acid (P5C) reductase homologue, were overexpressed in Escherichia coli and biochemically characterized. Putative substrates were synthesized to test enzyme substrate specificities, and deuterium labeling studies were carried out to reveal the stereospecificities of the enzymatic reactions with respect to the substrates as well as to the coenzymes.

  DOI：

  10.1021/jo026479q
• 作为产物：
  描述：

  L-亮氨酸 在 leucine 5-hydroxylase GriE 、 氧气 、 iron(II) sulfate 、 disodium α-ketoglutarate 、 维生素 C 作用下， 以 aq. phosphate buffer 为溶剂， 反应 5.0h， 以90%的产率得到(2S,4R)-5-hydroxyleucine
  参考文献：
  名称：

  α-酮戊二酸依赖性双加氧酶的远程 C-H 羟基化使 Manzacidin C 和脯氨酸类似物的高效化学酶法合成成为可能

  摘要：

  远端位置的选择性 CH 官能化仍然是有机合成中极具挑战性的问题。尽管大自然已经进化出无数能够实现这一壮举的酶，但它们的合成效用在很大程度上被忽视了。在这里，我们在功能上表征了一种α-酮戊二酸依赖性双加氧酶（Fe/αKG），它选择性地羟基化各种脂肪族氨基酸的 δ 位置。与催化类似反应的其他 Fe/αKG 相比，该酶的动力学分析和底物分析显示出优异的催化效率和底物混杂性。我们证明了这种转化在稀有生物碱、manzacin C 和密集取代的氨基酸衍生物的简洁合成中的实际效用，具有显着的步骤效率。

  DOI：

  10.1021/jacs.7b12918

文献信息

• Evolution of Biocatalytic and Chemocatalytic C–H Functionalization Strategy in the Synthesis of Manzacidin C
  作者：Christian R. Zwick、Hans Renata

  DOI：10.1021/acs.joc.8b00248

  日期：2018.7.20

  approaches toward manzacidin C that center on the enzymatic hydroxylation of unprotected l-leucine. This study also resulted in the discovery of novel synthetic methodologies, including a photocatalytic C–H azidation of unprotected amino acids. Additionally, we describe the use of hydroxylated l-leucine in the preparation of various densely substituted pyrrolidines.

  由于其独特的分子结构，在过去的二十年中，甘露糖苷一直是合成研究的重点。在这里，我们描述了两种针对山楂酸C的合成方法，它们以未受保护的1-亮氨酸的酶促羟基化为中心。这项研究还导致发现了新的合成方法，包括未保护氨基酸的光催化C–H叠氮化。另外，我们描述了羟基化的1-亮氨酸在制备各种紧密取代的吡咯烷中的用途。
• An Improved Turn Structure for Inducing β‐Hairpin Formation in Peptides
  作者：Xingyue Li、Andrew L. Sabol、Michał Wierzbicki、Patrick J. Salveson、James S. Nowick

  DOI：10.1002/anie.202105559

  日期：2021.10.11

  tool to coax any small peptide to adopt a β-hairpin conformation, regardless of sequence. Here, we report that δ-linked γ(R)-methyl-ornithine (δMeOrn) provides an improved β-turn template for inducing a β-hairpin conformation in peptides. We developed a synthesis of protected δMeOrn as a building block suitable for use in Fmoc-based solid-phase peptide synthesis. The synthesis begins with l-leucine

  尽管 β-发夹在蛋白质中广泛存在，但没有工具可以诱使任何小肽采用 β-发夹构象，无论序列如何。在这里，我们报告了 δ-连接的 γ( R )-甲基-鸟氨酸 ( δ MeOrn) 为诱导肽中的 β-发夹构象提供了改进的 β-转角模板。我们开发了一种受保护的δ MeOrn 合成方法，作为适用于基于 Fmoc 的固相肽合成的构建块。合成从l-亮氨酸开始并提供克数量的N α -Boc - N δ -Fmoc-γ( R )-甲基-鸟氨酸结构单元。X 射线晶体学证实δMeOrn 转角单元采用大环 β-发夹肽中的折叠结构。CD 和 NMR 光谱允许将δ MeOrn 转角模板与我们之前介绍的 δ-连接的鸟氨酸 ( δ Orn) 转角模板和流行的d -Pro-Gly 转角模板进行比较。这些研究表明，δ MeOrn 转角模板的折叠明显优于δ Orn，并且与d -Pro-Gly 相当。
• Gene cluster for biosynthesis of griselimycin and methylgriselimycin
  申请人：SANOFI

  公开号：EP2586791A1

  公开（公告）日：2013-05-01

  The present invention refers to the gene cluster and genes comprised by the gene cluster which are involved in the biosynthesis of griselimycin and methylgriselimycin and to the use of the gene cluster, genes comprised thereby and proteins encoded thereby for the production of antibiotic agents.

  本发明是指参与格氏霉素和甲基格氏霉素生物合成的基因簇和由该基因簇组成的基因，以及将该基因簇、由该基因簇组成的基因及其编码的蛋白质用于生产抗生素制剂。
• 3-Hydroxylysine, a Potential Marker for Studying Radical-Induced Protein Oxidation
  作者：Bénédicte Morin、William A. Bubb、Michael J. Davies、Roger T. Dean、Shanlin Fu

  DOI：10.1021/tx980118h

  日期：1998.11.1

  gamma-Irradiation of several amino acids (Val, Leu, lie, Lys, Pro, and Glu) in the presence of O-2 generates hydroperoxides. We have previously isolated and characterized valine and leucine hydroperoxides, and hydroxides, and have detected these products in both isolated systems [e.g., bovine serum albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore likely to be particularly susceptible to oxidation by radicals in bulk solution. HO. attack on lysine in the presence of oxygen, followed by NaBH4 reduction, is shown to give rise to (2S)-3-hydroxylysine [(2S)-2,6-diamino-3-hydroxyhexanoic acid], (2S)-4-hydroxylysine [(2S)-2,6-diamino-4-hydroxyhexanoic acid], (2S,5R)-5-hydroxylysine [(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid], and (2S,5S)-5-hydroxylysine [(2S,5S)-2,6-diamino-5-hydroxyhexanoic acid]. 5-Hydroxylysines are natural products formed by lysyl oxidase and are therefore not good markers of radical-mediated oxidation. The other hydroxylysines are however useful markers, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu-Phe) and proteins (BSA and histone H1) exposed to HO ./O-2, and subsequently treated with NaBH4. Quantification of the hydroxylysines yields, and comparison with hydroxyvalines and hydroxyleucines, supports the hypothesis that surface residues give higher yields of oxidized products than the hydrophobic leucines and valines, at least with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems.
• Belokon', Yuri N.; Bulychev, Aleksandr G.; Pavlov, Viacheslav A., Journal of the Chemical Society. Perkin transactions I, 1988, p. 2075 - 2084
  作者：Belokon', Yuri N.、Bulychev, Aleksandr G.、Pavlov, Viacheslav A.、Fedorova, Eugenia B.、Tsyryapkin, Vladimir A.、et al.

  DOI：——

  日期：——