Boc-Ala-(D)-iso-Glu-(OMe)-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe | 213532-18-4

• 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: Boc-Ala-(D)-iso-Glu-(OMe)-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe
• 英文别名: BOC-L-Ala-D-iso-Glu(OMe)-Nε-(TFA)-L-Lys-D-Ala-D-Ala-OMe；Boc-L-Ala-γ-D-Glu(OMe)-L-Lys(COCF3)-D-Ala-D-Ala-OMe；Boc-Ala-D-iso-Glu(OMe)-Lys(Tfa)-D-Ala-D-Ala-OMe；Boc-L-Ala-D-Glu(OMe)-L-Lys(OTf)-D-Ala-D-Ala-OMe；Boc-Ala-D-gGlu(OMe)-Lys(Tfa)-D-Ala-D-Ala-OMe；methyl (2R)-5-[[(2S)-1-[[(2R)-1-[[(2R)-1-methoxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-6-[(2,2,2-trifluoroacetyl)amino]hexan-2-yl]amino]-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-5-oxopentanoate
• CAS: 213532-18-4
• 化学式: C₂₉H₄₇F₃N₆O₁₁
• 分子量: 712.721
• InChiKey: DIWQFMXPKWMDRE-MTHXSQLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  49
• 可旋转键数：
  22
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  236
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  Boc-Ala-(D)-iso-Glu-(OMe)-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 H-Ala-D-iso-Glu(OMe)-Lys(Tfa)-D-Ala-D-Ala-OMe hydrochloride
  参考文献：
  名称：

  Transpeptidase-Mediated Incorporation of d-Amino Acids into Bacterial Peptidoglycan

  摘要：

  The beta-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse D-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical D-amino acids can be introduced into the bacterial cell wall.

  DOI：

  10.1021/ja2040656
• 作为产物：
  描述：

  N-叔丁氧羰基-D-谷氨酸 1-甲酯 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 92.0h， 生成 Boc-Ala-(D)-iso-Glu-(OMe)-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe
  参考文献：
  名称：

  Synthesis of a radioiodinated park nucleotide analog: a new tool for antibacterial screen development

  摘要：

  The Park nucleotide is an important biological building block used in the construction of bacterial cell walls. Herein, we describe the synthesis of a radiolabeled Park nucleotide analog, p-iodophenoxyacyl-Ala-(D)-iso-Glu-Lys-(D)-Ala-(D)-Ala-OH-[I-125], using electrophilic destannylation. Anti-Park nucleotide antibody binding assays using a scintillation proximity assay (SPA) system showed good recognition of the radiolabeled surrogate. This methodology could be used for establishing a screen to identify inhibitors of peptidoglycan biosynthesis.

  DOI：

  10.1002/(sici)1099-1344(1998080)41:8<705::aid-jlcr119>3.0.co;2-n

文献信息

• The Total Synthesis of Lipid I
  作者：Michael S. VanNieuwenhze、Scott C. Mauldin、Mohammad Zia-Ebrahimi、James A. Aikins、Larry C. Blaszczak

  DOI：10.1021/ja016082o

  日期：2001.7.1

  A total synthesis of lipid I (4), a membrane-associated intermediate in the bacterial cell wall (peptidoglycan) biosynthesis pathway, is reported. This highly convergent synthesis will enable further studies on bacterial resistance mechanisms and may provide insight toward the development of new chemotherapeutic agents with novel modes of action.

  据报道，脂质 I (4) 是细菌细胞壁（肽聚糖）生物合成途径中的膜相关中间体的全合成。这种高度趋同的合成将使对细菌耐药机制的进一步研究成为可能，并可能为开发具有新作用模式的新型化疗药物提供见解。
• A New Oxyma Derivative for Nonracemizable Amide-Forming Reactions in Water
  作者：Qinghui Wang、Yong Wang、Michio Kurosu

  DOI：10.1021/ol3013556

  日期：2012.7.6

  An Oxyma derivative, (2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyano-2-(hydroxyimino)acetate (2), displayed remarkable physicochemical properties as a peptide-coupling additive for peptide-forming reactions in water. Short peptides to oligopeptides could be synthesized by using 2, EDCI, and NaHCO3 in water without measurable racemization. Significantly, a simple basic and acidic aqueous workup procedure can remove all reagents utilized in the reactions to afford only coupling products in consistently excellent yields.
• N-Methylimidazolium chloride-catalyzed pyrophosphate formation: Application to the synthesis of Lipid I and NDP-sugar donors
  作者：Hirokazu Tsukamoto、Daniel Kahne

  DOI：10.1016/j.bmcl.2011.04.061

  日期：2011.9

  N-Methylimidazolium chloride is found to catalyze a coupling reaction between monophosphates and activated phosphorous-nitrogen intermediates such as a phosphorimidazolide and phosphoromorpholidate to form biologically important unsymmetrical pyrophosphate diesters. The catalyst is much more active, cheaper, and less explosive than 1H-tetrazole, known as the best catalyst for the pyrophosphate formation over a decade. The mild and neutral reaction conditions are compatible with allylic pyrophosphate formation in Lipid I syntheisis. (31)P NMR experiments suggest that the catalyst acts not only as an acid but also as a nucleophile to form cationic and electrophilic phosphor-N-methylimidazolide intermediates in the pyrophosphate formation. (c) 2011 Elsevier Ltd. All rights reserved.
• Transpeptidase-Mediated Incorporation of <scp>d</scp>-Amino Acids into Bacterial Peptidoglycan
  作者：Tania J. Lupoli、Hirokazu Tsukamoto、Emma H. Doud、Tsung-Shing Andrew Wang、Suzanne Walker、Daniel Kahne

  DOI：10.1021/ja2040656

  日期：2011.7.20

  The beta-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse D-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical D-amino acids can be introduced into the bacterial cell wall.
• Synthesis of a radioiodinated park nucleotide analog: a new tool for antibacterial screen development
  作者：Clark N. Eid、Michael J. Nesler、Mohammad Zia-Ebrahimi、Chuyn-Yeh Ernie Wu、Raymond Yao、Karen Cox、John Richardson

  DOI：10.1002/(sici)1099-1344(1998080)41:8<705::aid-jlcr119>3.0.co;2-n

  日期：1998.8

  The Park nucleotide is an important biological building block used in the construction of bacterial cell walls. Herein, we describe the synthesis of a radiolabeled Park nucleotide analog, p-iodophenoxyacyl-Ala-(D)-iso-Glu-Lys-(D)-Ala-(D)-Ala-OH-[I-125], using electrophilic destannylation. Anti-Park nucleotide antibody binding assays using a scintillation proximity assay (SPA) system showed good recognition of the radiolabeled surrogate. This methodology could be used for establishing a screen to identify inhibitors of peptidoglycan biosynthesis.