tert-Butyl (R)-(5-methylhex-1-en-3-yl)carbamate | 875322-16-0

• 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: tert-Butyl (R)-(5-methylhex-1-en-3-yl)carbamate
• 英文别名: tert-butyl N-[(3R)-5-methylhex-1-en-3-yl]carbamate
• CAS: 875322-16-0
• 化学式: C₁₂H₂₃NO₂
• 分子量: 213.32
• InChiKey: OOYLKAHPLMLJPK-JTQLQIEISA-N

物化性质

• 沸点：
  282.2±19.0 °C(Predicted)
• 密度：
  0.908±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-Butyl (R)-(5-methylhex-1-en-3-yl)carbamate 在 甲基磺酰胺 作用下， 以 水 、 叔丁醇 为溶剂， 反应 44.0h， 生成 tert-butyl N-[(3R)-1,2-dihydroxy-5-methylhexan-3-yl]carbamate
  参考文献：
  名称：

  Synthesis of New (−)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase

  摘要：

  The malarial PfA-M1 metalloaminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-D-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural a-amino add (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBz1) 16 at the 131 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PEA-M1 pocket that interacts with the PI side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.

  DOI：

  10.1021/jm101227t
• 作为产物：
  描述：

  甲基三苯基溴化膦 、 tert-butyl N-[(1R)-1-formyl-3-methyl-butyl]carbamate 在 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成 tert-Butyl (R)-(5-methylhex-1-en-3-yl)carbamate
  参考文献：
  名称：

  Synthesis of New (−)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase

  摘要：

  The malarial PfA-M1 metalloaminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-D-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural a-amino add (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBz1) 16 at the 131 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PEA-M1 pocket that interacts with the PI side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.

  DOI：

  10.1021/jm101227t

文献信息

• [EN] ANTIMICROBIAL COMPUNDS AND METHODS OF MAKING AND USING THE SAME<br/>[FR] COMPOSÉS ANTIMICROBIENS ET PROCÉDÉS DE FABRICATION ET D'UTILISATION DE CES COMPOSÉS
  申请人：MELINTA THERAPEUTICS INC

  公开号：WO2015035426A1

  公开（公告）日：2015-03-12

  The present invention relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, reducing the risk of, and delaying the onset of microbial infections in humans and animals.

  本发明通常涉及抗微生物化合物领域，以及制备和使用它们的方法。这些化合物可用于治疗、预防、降低人类和动物微生物感染的风险，并延迟其发作。
• Synthesis of New (−)-Bestatin-Based Inhibitor Libraries Reveals a Novel Binding Mode in the S1 Pocket of the Essential Malaria M1 Metalloaminopeptidase
  作者：Geetha Velmourougane、Michael B. Harbut、Seema Dalal、Sheena McGowan、Christine A. Oellig、Nataline Meinhardt、James C. Whisstock、Michael Klemba、Doron C. Greenbaum

  DOI：10.1021/jm101227t

  日期：2011.3.24

  The malarial PfA-M1 metalloaminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-D-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the alpha-hydroxy-beta-amino acid (P1) or the adjacent natural a-amino add (P1'). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBz1) 16 at the 131 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PEA-M1 pocket that interacts with the PI side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.