tert-butyl N-[(2R)-3,4-dihydroxy-1-(4-methoxyphenyl)butan-2-yl]carbamate | 1275576-33-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl N-[(2R)-3,4-dihydroxy-1-(4-methoxyphenyl)butan-2-yl]carbamate
• CAS: 1275576-33-4
• 化学式: C₁₆H₂₅NO₅
• 分子量: 311.378
• InChiKey: IIXHRLURSVIOTH-KWCCSABGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2R)-3,4-dihydroxy-1-(4-methoxyphenyl)butan-2-yl]carbamate 在 哌啶 、 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium chlorite 、 sodium chloride dihydrate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.0h， 生成 N-[(2S,3R)-3-amino-2-hydroxy-4-(4-methoxyphenyl)-butanoyl]-L-leucine
  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：

  (-)-(R)-N-(tert-butoxycarbonyl)-3-amino-4-(p-methyloxyphenyl)-1-butene 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-[(2R)-3,4-dihydroxy-1-(4-methoxyphenyl)butan-2-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