(S_CR_S)-L-methionine sulfoxide | 3226-66-2

• 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 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S_CR_S)-L-methionine sulfoxide
• 英文别名: (R_SS_C)-methionine sulfoxide；L-methionine (R_S)-sulfoxide；(S)-methionine (R)-sulfoxide；L-methionine-R-sulfoxide；L-methionine sulfoxide；methionine sulfoxide；(2S)-2-azaniumyl-4-[(R)-methylsulfinyl]butanoate
• CAS: 3226-66-2
• 化学式: C₅H₁₁NO₃S
• 分子量: 165.213
• InChiKey: QEFRNWWLZKMPFJ-ZXPFJRLXSA-N

物化性质

• 沸点：
  434.3±40.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  99.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl (2S)-2-(methoxycarbonylamino)-4-methylthiobutyrate 在 双氧水 、 chloroperoxidase 、 barium dihydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 5.25h， 以62 mg的产率得到(S_CR_S)-L-methionine sulfoxide
  参考文献：
  名称：

  Chloroperoxidase-catalyzed oxidation of methionine derivatives

  摘要：

  氯过氧化酶-过氧化氢对N-甲氧羰基C-羧酸酯衍生物的L-和D-蛋氨酸以及L-依氨酸进行处理，导致硫原子氧化产生(RS)亚硫氧化物，其对映异构体过量为中等到高。甲硫氧化物也可通过α-胰蛋白酶、曲霉孢蛋白酶或卡尔斯堡亚硫酸酯水解从(±)SO-N-甲氧羰基-L-蛋氨酸甲酯亚硫酸酯中以中等到高的对映异构体过量获得。关键词：氨基酸氧化、生物催化、生物转化、氯过氧化酶、酶催化、脂肪酶、亚硫氧化。

  DOI：

  10.1139/v02-025

文献信息

• Identification of a lysine 4-hydroxylase from the glidobactin biosynthesis and evaluation of its biocatalytic potential
  作者：Alexander Amatuni、Hans Renata

  DOI：10.1039/c8ob02054j

  日期：——

  We present the functional characterization of GlbB, a lysine 4-hydroxylase from the glidobactin biosynthetic gene cluster. Despite its narrow substrate specificity, GlbB is able to catalyze the hydroxylation of l-lysine with excellent total turnover number and complete regio- and diastereoselectivity. The synthetic utility of GlbB is illustrated by its use in the efficient preparation of a key dipeptide

  我们目前的功能表征GlbB，从glidobactin生物合成基因簇的赖氨酸4-羟化酶。尽管其底物特异性狭窄，但是GlbB能够以优异的总周转数以及完全的区域和非对映选择性催化L-赖氨酸的羟基化。GlbB在有效制备格列葡汀的关键二肽片段中的应用说明了GlbB的合成效用。
• Remote C–H Hydroxylation by an α-Ketoglutarate-Dependent Dioxygenase Enables Efficient Chemoenzymatic Synthesis of Manzacidin C and Proline Analogs
  作者：Christian R. Zwick、Hans Renata

  DOI：10.1021/jacs.7b12918

  日期：2018.1.24

  demonstrate the practical utility of this transformation in the concise syntheses of a rare alkaloid, manzacidin C, and densely substituted amino acid derivatives with remarkable step efficiency. This work provides a blueprint for future applications of Fe/αKG hydroxylation in complex molecule synthesis and the development of powerful synthetic paradigms centered on enzymatic C-H functionalization logic

  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。
• Probing the stereochemistry of the active site of gamma-glutamyl transpeptidase using sulfur derivatives of l-glutamic acid
  作者：Christian Lherbet、Jeffrey W. Keillor

  DOI：10.1039/b310767a

  日期：——

  Gamma-glutamyl transpeptidase (GGT) catalyses the transfer of a γ-glutamyl moiety from a donor substrate to different acceptors, such as amino acids and water. GGT is known to display relatively low stereospecificity with respect to the α-stereocentre of its donor substrates. In this study we have studied its stereospecificity with respect to the stereocentre at the δ-position of different analogues of L-glutamic acid. Notably, L-methionine sulfoxide is well-recognised whereas L-methionine sulfone and L-methionine sulfoximine are not. Furthermore, when the synthetic γ-diastereoisomers of L-methionine sulfoxide were separated and tested, it was discovered that GGT shows remarkable stereospecificity at the γ-position, binding the SCSS diastereoisomer with a Ki of 3.5 mM, whereas the SCRS diastereoisomer is not recognised. Finally, using a sulfoxide as a new pharmacophore for GGT, we have synthesized and tested an analogue of glutathione to obtain a very promising competitive inhibitor with a Ki of (53 ± 3) µM.

  γ-谷氨酰转肽酶 (GGT) 催化 γ-谷氨酰部分从供体底物转移到不同的受体，例如氨基酸和水。已知 GGT 相对于其供体底物的 α-立体中心表现出相对较低的立体特异性。在本研究中，我们研究了其相对于 L-谷氨酸不同类似物的 δ 位立体中心的立体特异性。值得注意的是，L-甲硫氨酸亚砜已被广泛认可，而 L-甲硫氨酸砜和 L-甲硫氨酸亚砜亚胺则不然。此外，当分离和测试合成的L-蛋氨酸亚砜的γ-非对映异构体时，发现GGT在γ-位表现出显着的立体特异性，以3.5 mM的Ki结合SCSS非对映异构体，而SCRS非对映异构体则未被识别。最后，使用亚砜作为GGT的新药效团，我们合成并测试了谷胱甘肽的类似物，获得了一种非常有前途的竞争性抑制剂，其Ki为（53±3） µM。
• Synthesis of Methionine-Derived Endocyclic Sulfilimines and Sulfoximines
  作者：Hamid Marzag、Marie Schuler、Arnaud Tatibouët、Vincent Reboul

  DOI：10.1002/ejoc.201601515

  日期：2017.1.26

  was obtained and a deprotonation step by t-BuONa is necessary, to yield the corresponding sulfilimine. On the other hand, cyclic sulfilimine of methionine methyl ester, methylthiopropylamine and L methioninol were synthetized in a single step using PIDA. Due to their instability, the sulfilimines were oxidized into corresponding sulfoximine in good yields.

  报道了从甲硫氨酸衍生物不对称合成内环甲硫氨酸硫亚胺和亚砜亚胺。环化使用二乙酸苯碘 (PIDA) 进行。在 L-甲硫氨酸的情况下，获得脱氢甲硫氨酸并且需要通过 t-BuONa 进行去质子化步骤，以产生相应的硫亚胺。另一方面，使用 PIDA 一步合成甲硫氨酸甲酯、甲硫基丙胺和 L 甲硫氨醇的环状硫亚胺。由于它们的不稳定性，硫亚胺以良好的产率被氧化成相应的亚砜亚胺。
• Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons
  作者：Alexandra Gennaris、Benjamin Ezraty、Camille Henry、Rym Agrebi、Alexandra Vergnes、Emmanuel Oheix、Julia Bos、Pauline Leverrier、Leon Espinosa、Joanna Szewczyk、Didier Vertommen、Olga Iranzo、Jean-François Collet、Frédéric Barras

  DOI：10.1038/nature15764

  日期：2015.12

  The identification of an enzymatic system repairing proteins containing oxidized methionine in the bacterial cell envelope, a compartment particularly susceptible to oxidative damage by host defence mechanisms. Frédéric Barras and colleagues report the identification of an enzyme system, MsrPQ, which repairs a wide range of periplasmic proteins with oxidatively damaged methionine (methionine sulfoxide, Met-O) in the bacterial cell envelope, a compartment that is particularly susceptible to oxidative damage by host defence mechanisms. MsrP and MsrQ are widely distributed in Gram-negative bacteria and are expressed following exposure to hypochlorous acid, a powerful antimicrobial agent that is released by neutrophils. Interestingly, the MsrPQ repair system is functionally distinct from conventional methionine sulfoxide reductases as it exhibits non-stereospecificity and can reduce both R- and S-diastereoisomers of Met-O. Furthermore, the authors report a novel mechanism of action for MsrPQ in which electrons from the respiratory chain are used for reducing power, establishing a new link between metabolism and cellular integrity. The reactive species of oxygen and chlorine damage cellular components, potentially leading to cell death. In proteins, the sulfur-containing amino acid methionine is converted to methionine sulfoxide, which can cause a loss of biological activity. To rescue proteins with methionine sulfoxide residues, living cells express methionine sulfoxide reductases (Msrs) in most subcellular compartments, including the cytosol, mitochondria and chloroplasts1,2,3. Here we report the identification of an enzymatic system, MsrPQ, repairing proteins containing methionine sulfoxide in the bacterial cell envelope, a compartment particularly exposed to the reactive species of oxygen and chlorine generated by the host defence mechanisms. MsrP, a molybdo-enzyme, and MsrQ, a haem-binding membrane protein, are widely conserved throughout Gram-negative bacteria, including major human pathogens. MsrPQ synthesis is induced by hypochlorous acid, a powerful antimicrobial released by neutrophils. Consistently, MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing a wide series of structurally unrelated periplasmic proteins from methionine oxidation, including the primary periplasmic chaperone SurA. For this activity, MsrPQ uses electrons from the respiratory chain, which represents a novel mechanism to import reducing equivalents into the bacterial cell envelope. A remarkable feature of MsrPQ is its capacity to reduce both rectus (R-) and sinister (S-) diastereoisomers of methionine sulfoxide, making this oxidoreductase complex functionally different from previously identified Msrs. The discovery that a large class of bacteria contain a single, non-stereospecific enzymatic complex fully protecting methionine residues from oxidation should prompt a search for similar systems in eukaryotic subcellular oxidizing compartments, including the endoplasmic reticulum.

  鉴定出一种酶系统可修复细菌细胞包膜中含有氧化蛋氨酸的蛋白质，而细菌细胞包膜是一个特别容易受到宿主防御机制氧化损伤的区域。Frédéric Barras及其同事报告了一种酶系统MsrPQ的鉴定结果，该酶系统可修复细菌细胞包膜中含有氧化损伤的蛋氨酸（蛋氨酸亚砜，Met-O）的多种包膜蛋白质，而细菌细胞包膜是一个特别容易受到宿主防御机制氧化损伤的区域。MsrP 和 MsrQ 广泛分布于革兰氏阴性细菌中，在接触中性粒细胞释放的强效抗菌剂次氯酸后会表达。有趣的是，MsrPQ 修复系统在功能上有别于传统的蛋氨酸亚砜还原酶，因为它表现出非立体特异性，可以还原 Met-O 的 R-和 S-非对映异构体。此外，作者还报告了 MsrPQ 的一种新作用机制，即利用呼吸链中的电子进行还原，从而在新陈代谢和细胞完整性之间建立起一种新的联系。氧和氯的活性物种会破坏细胞成分，可能导致细胞死亡。在蛋白质中，含硫氨基酸蛋氨酸会转化为蛋氨酸亚砜，从而导致生物活性丧失。为了挽救含有蛋氨酸亚砜残基的蛋白质，活细胞在大多数亚细胞区室（包括细胞质、线粒体和叶绿体）中都表达蛋氨酸亚砜还原酶（Msrs）1,2,3。在这里，我们报告了一种酶系统--MsrPQ--的发现，它能修复细菌细胞包膜中含有蛋氨酸亚砜的蛋白质，而细菌细胞包膜是一个特别容易受到宿主防御机制产生的氧和氯等活性物种影响的区室。MsrP 是一种钼酵素，MsrQ 是一种血红素结合膜蛋白，它们在革兰氏阴性细菌（包括主要的人类病原体）中广泛保守。次氯酸是中性粒细胞释放的一种强力抗菌剂，可诱导 MsrPQ 的合成。在漂白压力下，MsrPQ 对维持包膜完整性至关重要，它能从蛋氨酸氧化中挽救一系列结构上不相关的包膜蛋白质，包括主要的包膜伴侣 SurA。为了实现这种活性，MsrPQ 使用了来自呼吸链的电子，这是一种将还原等价物导入细菌细胞包膜的新机制。MsrPQ 的一个显著特点是它有能力还原蛋氨酸亚砜的直向（R-）和阴向（S-）非对映异构体，这使得这种氧化还原酶复合物在功能上有别于以前发现的 Msrs。 发现一大类细菌含有一种单一的、非立体特异性的酶复合物，能完全保护蛋氨酸残基不被氧化，这应促使人们在真核生物亚细胞氧化区（包括内质网）中寻找类似的系统。