(S_CS_S)-L-methionine sulfoxide | 23631-84-7

• 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_CS_S)-L-methionine sulfoxide
• 英文别名: (S_SS_C)-methionine sulfoxide；(S)-methionine (S)-sulfoxide；L-methionine (S)-sulfoxide；L-methionine-S-sulfoxide；L-methionine sulfoxide；L-Met(S)SO；(2S)-2-azaniumyl-4-[(S)-methylsulfinyl]butanoate
• CAS: 23631-84-7
• 化学式: C₅H₁₁NO₃S
• 分子量: 165.213
• InChiKey: QEFRNWWLZKMPFJ-MFXDVPHUSA-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

• 作为反应物：
  描述：

  (S_CS_S)-L-methionine sulfoxide 在 乙二胺四乙酸 、 trypanoredoxin I 、 Trypanosoma cruzi N-terminally His-tagged methionine sulfoxide reductase type A 、 Trypanosoma cruzi trypanothione reductase 、 trypanothione 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 L-蛋氨酸
  参考文献：
  名称：

  Functional characterization of methionine sulfoxide reductase A from Trypanosoma spp.

  摘要：

  Methionine is an amino acid susceptible to being oxidized to methionine sulfoxide (MetSO). The reduction of MetSO to methionine is catalyzed by methionine sulfoxide reductase (MSR), an enzyme present in almost all organisms. In trypanosomatids, the study of antioxidant systems has been mainly focused on the involvement of trypanothione, a specific redox component in these organisms. However, no information is available concerning their mechanisms for repairing oxidized proteins, which would be relevant for the survival of these pathogens in the various stages of their life cycle. We report the molecular cloning of three genes encoding a putative A-type MSR in trypanosomatids. The genes were expressed in Escherichia coli, and the corresponding recombinant proteins were purified and functionally characterized. The enzymes were specific for L-Met(S)SO reduction, using Trypanosoma cruzi tryparedoxin I as the reducing substrate. Each enzyme migrated in electrophoresis with a particular profile reflecting the differences they exhibit in superficial charge. The in vivo presence of the enzymes was evidenced by immunological detection in replicative stages of T cruzi and Trypanosoma brucei. The results support the occurrence of a metabolic pathway in Trypanosoma Spp. involved in the critical function of repairing oxidized macromolecules. (C) 2010 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.freeradbiomed.2010.10.695
• 作为产物：
  描述：

  L-蛋氨酸 在 DL-dithiothreitol 、 iron(II) sulfate 作用下， 以 aq. buffer 为溶剂， 反应 16.0h， 以90%的产率得到
  参考文献：
  名称：

  Enzymatic synthesis of chiral amino acid sulfoxides by Fe(II)/α-ketoglutarate-dependent dioxygenase

  摘要：

  Asymmetric sulfoxidation of sulfur-containing L-amino acids was successfully achieved through bioconversion using IDO, which is an Fe(II)/alpha-ketoglutarate-dependent dioxygenase previously found in Bacillus thuringiensis strain 2e2. The IDO catalyzed sulfoxidation of L-methionine, L-ethionine, S-methyl-L-cysteine, S-ethyl-L-cysteine, and S-allyl-L-cysteine into the corresponding (S)-configured sulfoxides such as (+)-methiin and (+)-alliin, which are responsible for valuable physiological activities in mammals, and have high stereoselectivity. Herein we have established an effective preparative laboratory scale production method to obtain enantiomerically pure chiral sulfoxides using an IDO biocatalyst. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.07.017

文献信息

• Synthesis of New Chiral Phase-transfer Catalysts and Their Application to Michael Additions
  作者：Stefano Banfi、Mauro Cinquini、Stefano Colonna

  DOI：10.1246/bcsj.54.1841

  日期：1981.6

  A series of chiral onium salts derived from (L)-(+)-methionine have been examined for the catalysis of Michael additions in phase-transfer conditions. The chemical yields are high, but no asymmetric induction was observed. Catalyst 6 represents the first example of an onium salt anchored to a polimeric matrix having a higher catalytic efficiency than its soluble counterpart.

  已经研究了一系列衍生自 (L)-(+)-甲硫氨酸的手性鎓盐在相转移条件下对迈克尔加成的催化作用。化学产率高，但未观察到不对称诱导。催化剂6代表了锚定在聚合物基质上的鎓盐的第一个例子，其具有比其可溶性对应物更高的催化效率。
• 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。
• Derivate von L-Methionin-sulfoxyd und ihre Verwendung für Peptidsynthesen
  作者：B. Iselin

  DOI：10.1002/hlca.19610440109

  日期：——

  The unwanted side reactions often encountered in the synthesis of methionine containing peptides can be eliminated by a temporary conversion of the thioether function of methionine into the sulfoxide at any stage of a peptide synthesis. The sulfoxide oxygen is introduced without the formation of a sulfone when a small excess of hydrogen peroxide is used, and its elimination is easily achieved by reduction

  可以通过在肽合成的任何阶段将蛋氨酸的硫醚官能团暂时转化为亚砜来消除合成蛋氨酸肽时经常遇到的有害副反应。当使用少量过量的过氧化氢时，引入亚砜氧气而不会形成砜，并且通过用巯基乙酸还原可以很容易地消除亚砜氧气。与蛋氨酸的羰基苯并氧衍生物相反，通过用浓盐酸进行温和处理，顺利地从相应的亚砜中除去了羰基苯并氧羰基。描述了使用该方法合成肽衍生物H pro-Tyr-Lys（Tos）-Met OH。
• 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。