Boc-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe | 213532-16-2

• 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-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe
• 英文别名: Nα-Boc-Nε-(TFA)-L-Lys-D-Ala-D-Ala-OMe；Boc-Lys(Tfa)-D-Ala-D-Ala-OMe；methyl (2R)-2-[[(2R)-2-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-6-[(2,2,2-trifluoroacetyl)amino]hexanoyl]amino]propanoyl]amino]propanoate
• CAS: 213532-16-2
• 化学式: C₂₀H₃₃F₃N₄O₇
• 分子量: 498.5
• InChiKey: HDTZAGMSVAZXOU-UPJWGTAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Boc-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 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：

  D-丙氨酰-D-丙氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 乙酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 Boc-Lys-(N^ε-COCF3)-(D)-Ala-(D)-Ala-OMe
  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

文献信息

• One-Pot Protection-Glycosylation Reactions for Synthesis of Lipid II Analogues
  作者：Katsuhiko Mitachi、Priya Mohan、Shajila Siricilla、Michio Kurosu

  DOI：10.1002/chem.201400307

  日期：2014.4.14

  applied to a one‐pot protection‐glycosylation reaction to form the disaccharide derivative 7 d for the synthesis of lipid II analogues. The temporary protecting group or linker at the C‐6 position and N‐Troc protecting group of 7 d can be cleaved simultaneously through a reductive condition. Overall yields of syntheses of lipid II (1) and neryl‐lipid II Nε‐dansylthiourea are significantly improved by

  (2,6-二氯-4-甲氧基苯基)(2,4-二氯苯基)甲基三氯乙酰亚胺酯( 3 )及其聚合物支撑试剂4可成功应用于一锅保护糖基化反应，形成二糖衍生物7d 用于合成脂质 II 类似物。C-6位的临时保护基或连接基和7d的N -Troc保护基可以通过还原条件同时裂解。通过使用所描述的方法，脂质 II ( 1 ) 和橙花基脂质 II N ε -丹磺基硫脲的合成总产率显着提高。
• The First Total Synthesis of Lipid II:  The Final Monomeric Intermediate in Bacterial Cell Wall Biosynthesis
  作者：Michael S. VanNieuwenhze、Scott C. Mauldin、Mohammad Zia-Ebrahimi、Brian E. Winger、William J. Hornback、Shankar L. Saha、James A. Aikins、Larry C. Blaszczak

  DOI：10.1021/ja017386d

  日期：2002.4.1

  Bacterial peptidoglycan is composed of a network of beta-[1,4]-linked glyan strands that are cross-linked through pendant peptide chains. The final product, the murein sacculus, is a single, covalently closed macromolecule that precisely defines the size and shape of the bacterial cell. The recent increase in bacterial resistance to cell wall active agents has led to a resurgence of activity directed

  细菌肽聚糖由通过悬垂肽链交联的β-[1,4]-连接的聚糖链网络组成。最终产物，胞壁质球囊，是一个单一的、共价闭合的大分子，它精确地定义了细菌细胞的大小和形状。最近细菌对细胞壁活性剂耐药性的增加导致了旨在提高我们对分子水平耐药机制理解的活动的复苏。生物合成酶及其天然底物可以成为这一努力的宝贵工具。虽然现代实验技术已经导致肽聚糖生物合成中使用的生物合成酶的分离和纯化，但从天然底物中确保其必需底物的有用数量仍然存在问题。
• 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。
• Insights into the Mechanism of Action of the Two-Peptide Lantibiotic Lacticin 3147
  作者：Alireza Bakhtiary、Stephen A. Cochrane、Pascal Mercier、Ryan T. McKay、Mark Miskolzie、Clarissa S. Sit、John C. Vederas

  DOI：10.1021/jacs.7b04728

  日期：2017.12.13

  LtnA2) that displays nanomolar activity against many Gram-positive bacteria. Lacticin 3147 may exert its antimicrobial effect by several mechanisms. Isothermal titration calorimetry experiments show that only LtnA1 binds to the peptidoglycan precursor lipid II, which could inhibit peptidoglycan biosynthesis. An experimentally supported model of the resulting complex suggests that the key binding partners

  Lacticin 3147 是一种双肽 lantibiotc（LtnA1 和 LtnA2），对许多革兰氏阳性菌显示出纳摩尔级的活性。Lacticin 3147 可能通过多种机制发挥其抗菌作用。等温滴定量热实验表明，只有 LtnA1 与肽聚糖前体脂质 II 结合，可以抑制肽聚糖的生物合成。所得复合物的实验支持模型表明，关键的结合伙伴是 LtnA1 的 C 端和脂质 II 的焦磷酸盐。体内和体外检测的组合表明 LtnA1 和 LtnA2 可以诱导快速膜裂解，而无需脂质 II 结合。然而，脂质 II 的存在大大增加了乳酸菌素 3147 的活性。此外，
• 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.