N,N'-((3S,7S,11S)-11-(2,3-dihydroxy-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecane-3,7-diyl)bis(2,3-dihydroxybenzamide) | 851900-99-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N,N'-((3S,7S,11S)-11-(2,3-dihydroxy-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecane-3,7-diyl)bis(2,3-dihydroxybenzamide)
• 英文别名: Monoglucosyl-enterobactin；N-[(3S,7S,11S)-7,11-bis[(2,3-dihydroxybenzoyl)amino]-2,6,10-trioxo-1,5,9-trioxacyclododec-3-yl]-2,3-dihydroxy-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]benzamide
• CAS: 851900-99-7
• 化学式: C₃₆H₃₇N₃O₂₀
• 分子量: 831.698
• InChiKey: OZCSADRHPOQOPI-AEZKMRPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  59
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  378
• 氢给体数：
  13
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  尿苷(5')二氢二磷酰(1)-alpha-D-葡萄糖 、 N,N'-((3S,7S,11S)-11-(2,3-dihydroxy-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecane-3,7-diyl)bis(2,3-dihydroxybenzamide) 在 三(2-羰基乙基)磷盐酸盐 、 magnesium chloride 作用下， 以 水 为溶剂， 生成 salmochelin S4
  参考文献：
  名称：

  Biosynthetic Tailoring of Microcin E492m:  Post-translational Modification Affords an Antibacterial Siderophore−Peptide Conjugate

  摘要：

  The present work reveals that four proteins, MceCDIJ, encoded by the MccE492 gene cluster are responsible for the remarkable post-translational tailoring of microcin E492 (MccE492), an 84-residue protein toxin secreted by Klebsiella pheumonaie RYC492 that targets neighboring Gram-negative species. This modification results in attachment of a linearized and monoglycosylated derivative of enterobactin, a nonribosomal peptide and iron scavenger (siderophore), to the MccE492m C-terminus. MceC and MceD derivatize enterobactin by C-glycosylation at the C5 position of a N-(2,3-dihydroxybenzoyl)serine (DHB-Ser) moiety and regiospecific hydrolysis of an ester linkage in the trilactone scaffold, respectively. Mcel and MceJ form a protein complex that attaches C-glycosylated enterobactins to the C-terminal serine residue of both a C-10 model peptide and full-length MccE492. In the enzymatic product, the C-terminal serine residue is covalently attached to the C4'oxygen of the glucose moiety. Nonenzymatic and base-catalyzed migration of the peptide to the C6' position affords the C6' glycosyl ester linkage observed in the mature toxin, MccE492m, isolated from bacterial cultures.

  DOI：

  10.1021/ja074650f
• 作为产物：
  描述：

  N,N'-((3S,7S,11S)-11-(2,3-bis(benzyloxy)-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-2H-pyran-2-yl)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecane-3,7-diyl)bis(2,3-bis(benzyloxy)benzamide) 在 20 % Pd(OH)2/C 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 18.05h， 生成 N,N'-((3S,7S,11S)-11-(2,3-dihydroxy-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)benzamido)-2,6,10-trioxo-1,5,9-trioxacyclododecane-3,7-diyl)bis(2,3-dihydroxybenzamide)
  参考文献：
  名称：

  Facile synthesis of salmochelin S1, S2, MGE, DGE, and TGE

  摘要：

  Salmochelin S1, S2, MGE, DGE, and TGE were prepared through amide bond connection of an aryl C-glucosyl acyl chloride ((ArCOCl)-C-1) and serine ester amines, followed by hydrogenolysis of the per-benzylated precursors. Each synthesis employed a highly diastereoselective Ni-catalyzed Negishi approach to the aryl C-glycoside subunit. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2010.11.007

文献信息

• <i>In vitro</i> characterization of IroB, a pathogen-associated <i>C</i> -glycosyltransferase
  作者：Michael A. Fischbach、Hening Lin、David R. Liu、Christopher T. Walsh

  DOI：10.1073/pnas.0408463102

  日期：2005.1.18

  Pathogenic strains of Escherichia coli and Salmonella enterica modify the tricatecholic siderophore enterobactin (Ent) by glucosylation of three aryl carbon atoms, a process controlled by the iroA locus [Hantke, K., Nicholson, G., Rabsch, W. & Winkelmann, G. (2003) Proc. Natl. Acad. Sci. USA 100, 3677–3682]. Here, we report the purification of the IroB protein and its characterization as the Ent C -glucosyltransferase. IroB transfers glucosyl groups from uridine-5′-diphosphoglucose to C5 of one, two, or three of the 2,3-dihydroxybenzoyl units of Ent to yield monoglucosyl- C -Ent (MGE), diglucosyl- C -Ent (DGE), and triglucosyl- C -Ent (TGE). DGE, also known as salmochelin S4, and macrolactone-opened derivatives have been isolated from the culture broths of S. enterica and uropathogenic E. coli [Bister, B., Bischoff, D., Nicholson, G. J., Valdebenito, M., Schneider, K., Winkelmann, G., Hantke, K. & Sussmuth, R. D. (2004) Biometals 17, 471–481], but MGE and TGE have not been reported previously. IroB has a k _cat of ≈10 min ^-1 for the first C-glucosylation and is distributive, with sequential conversion and buildup of MGE and then DGE. The C5 to C1′ regio-selectivity of the 2,3-dihydroxybenzoyl-glucose linkage at all three rings of TGE suggests a C5 carbanion, para to the C2 phenolate oxygen, as the carbon nucleophile in this novel enzymatic C -glucosylation.

  致病菌株的大肠杆菌和沙门氏菌通过对三个芳香碳原子进行葡萄糖基化的方式改变三羟基三酚类铁载体内肠菌素（Ent），这一过程由iroA基因位点控制。在这里，我们报告了IroB蛋白的纯化及其作为Ent C-葡萄糖基转移酶的特性。IroB将葡萄糖基从尿苷-5'-二磷酸葡萄糖转移至Ent的2,3-二羟基苯甲酰单元的C5，可产生单葡萄糖基-C-Ent（MGE）、双葡萄糖基-C-Ent（DGE）和三葡萄糖基-C-Ent（TGE）。DGE，也称为沙门氏菌素S4，和大环内酯开放衍生物已从沙门氏菌和尿路致病性大肠杆菌的培养基中分离出来，但MGE和TGE以前尚未报道。IroB对第一次C-葡萄糖基化的kcat约为10分钟^-1，是分布式的，随着MGE和DGE的顺序转化和积累。TGE三个环上2,3-二羟基苯甲酰-葡萄糖连接的C5到C1'区域选择性表明C5碳负离子，即C2酚氧的对位，是这种新型酶促C-葡萄糖基化的碳亲核试剂。
• In Vitro Characterization of Salmochelin and Enterobactin Trilactone Hydrolases IroD, IroE, and Fes
  作者：Hening Lin、Michael A. Fischbach、David R. Liu、Christopher T. Walsh

  DOI：10.1021/ja0522027

  日期：2005.8.1

  The iroA locus encodes five genes (iroB, iroC, iroD, iroE, iroN) that are found in pathogenic Salmonella and Escherichia coli strains. We recently reported that IroB is an enterobactin (Ent) C-glucosyltransferase, converting the siderophore into mono-, di-, and triglucosyl enterobactins (MGE, DGE, and TGE, respectively). Here, we report the characterization of IroD and IroE as esterases for the apo and Fe3+-bound forms of Ent, MGE, DGE, and TGE, and we compare their activities with those of Fes, the previously characterized enterobactin esterase. IroD hydrolyzes both apo and Fe3+-bound siderophores distributively to generate DHB-Ser and/or Glc-DHB-Ser, with higher catalytic efficiencies (k(cat)/K-m) on Fe3+-bound forms, suggesting that IroD is the ferric MGE/DGE esterase responsible for cytoplasmic iron release. Similarly, Fes hydrolyzes ferric Ent more efficiently than apo Ent, confirming Fes is the ferric Ent esterase responsible for Fe3+ release from ferric Ent. Although each enzyme exhibits lower k(cat)'s processing ferric siderophores, dramatic decreases in K-m's for ferric siderophores result in increased catalytic efficiencies. The inability of Fes to efficiently hydrolyze ferric MGE, ferric DGE, or ferric TGE explains the requirement for IroD in the iroA cluster. IroE, in contrast, prefers apo siderophores as substrates and tends to hydrolyze the trilactone just once to produce linearized trimers. These data and the periplasmic location of IroE suggest that it hydrolyzes apo enterobactins while they are being exported. IroD hydrolyzes apo MGE (and DGE) regioselectively to give a single linear trimer product and a single linear dimer product as determined by NMR.
• Facile synthesis of salmochelin S1, S2, MGE, DGE, and TGE
  作者：Xiaolong Yu、Yijing Dai、Tao Yang、Michel R. Gagné、Hegui Gong

  DOI：10.1016/j.tet.2010.11.007

  日期：2011.1

  Salmochelin S1, S2, MGE, DGE, and TGE were prepared through amide bond connection of an aryl C-glucosyl acyl chloride ((ArCOCl)-C-1) and serine ester amines, followed by hydrogenolysis of the per-benzylated precursors. Each synthesis employed a highly diastereoselective Ni-catalyzed Negishi approach to the aryl C-glycoside subunit. (C) 2010 Elsevier Ltd. All rights reserved.
• Biosynthetic Tailoring of Microcin E492m:  Post-translational Modification Affords an Antibacterial Siderophore−Peptide Conjugate
  作者：Elizabeth M. Nolan、Michael A. Fischbach、Alexander Koglin、Christopher T. Walsh

  DOI：10.1021/ja074650f

  日期：2007.11.1

  The present work reveals that four proteins, MceCDIJ, encoded by the MccE492 gene cluster are responsible for the remarkable post-translational tailoring of microcin E492 (MccE492), an 84-residue protein toxin secreted by Klebsiella pheumonaie RYC492 that targets neighboring Gram-negative species. This modification results in attachment of a linearized and monoglycosylated derivative of enterobactin, a nonribosomal peptide and iron scavenger (siderophore), to the MccE492m C-terminus. MceC and MceD derivatize enterobactin by C-glycosylation at the C5 position of a N-(2,3-dihydroxybenzoyl)serine (DHB-Ser) moiety and regiospecific hydrolysis of an ester linkage in the trilactone scaffold, respectively. Mcel and MceJ form a protein complex that attaches C-glycosylated enterobactins to the C-terminal serine residue of both a C-10 model peptide and full-length MccE492. In the enzymatic product, the C-terminal serine residue is covalently attached to the C4'oxygen of the glucose moiety. Nonenzymatic and base-catalyzed migration of the peptide to the C6' position affords the C6' glycosyl ester linkage observed in the mature toxin, MccE492m, isolated from bacterial cultures.