(R)-2-(dimethylamino)-4-methylpentanoic acid | 174785-98-9

• 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: (R)-2-(dimethylamino)-4-methylpentanoic acid
• 英文别名: N,N-dimethyl-D-leucine；(2R)-2-(dimethylamino)-4-methylpentanoicacid；(2R)-2-(dimethylamino)-4-methylpentanoic acid
• CAS: 174785-98-9
• 化学式: C₈H₁₇NO₂
• 分子量: 159.228
• InChiKey: FZLYRJBAUQHHIH-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-(dimethylamino)-4-methylpentanoic acid 、 2-((1R,3R)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-1-acetoxy-4-methylpentyl)thiazole-4-carboxylic acid 、 (2S,4R)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methyl-5-phenylpentanoic acid 、 Fmoc-Ile-F 、 三氟乙酸 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.08h， 以0.032 g的产率得到(2S,4R)-4-(2-((3R,6S,9R,11R)-6-((S)-sec-butyl)-3-isobutyl-9-isopropyl-2,8-dimethyl-4,7,13-trioxo-12-oxa-2,5,8-triazatetradecan-11-yl)thiazole-4-carboxamido)-2-methyl-5-phenylpentanoic acid trifluoroacetate
  参考文献：
  名称：

  Structure–Cytotoxicity Relationships of Analogues of N¹⁴-Desacetoxytubulysin H

  摘要：

  Herein we report structure-cytotoxicity relationships for analogues of N-14-desacetoxytubulyisn H 1. A novel synthetic approach toward 1 enabled the discovery of compounds with a range of activity. Calculated basicity of the N-terminus of tubulysins was shown to be a good predictor of cytotoxicity. The impact of structural modifications at the C-terminus of 1 upon cytotoxicity is also described. These findings will facilitate the development of new tubulysin analogues for the treatment of cancer.

  DOI：

  10.1021/acs.jmedchem.6b01023
• 作为产物：
  描述：

  聚合甲醛 、 D-亮氨酸 在 palladium on activated charcoal 氢气 作用下， 以 水 为溶剂， 以53%的产率得到(R)-2-(dimethylamino)-4-methylpentanoic acid
  参考文献：
  名称：

  IB-01212, a New Cytotoxic Cyclodepsipeptide Isolated from the Marine Fungus Clonostachys sp. ESNA-A009

  摘要：

  IB-01212, a new cytotoxic cyclodepsipeptide featuring C-2 symmetry, was isolated from the mycelium extract of Clonostachys sp. ESNA-A009. The amino acid sequence of the compound was determined by spectroscopy techniques. The absolute configuration of the amino acids was determined by a combination of the Marfey and menthol methods. The structure, which was confirmed by comparison of the analytical data for the natural product with a sample obtained by solid-phase peptide synthesis, was revealed to be a cyclic dimer formed by two chains of L-N,N-Me(2)Leu-L-Ser-L-N-MeLeu-L-N-MePhe bound by the two esters formed between the carboxylic acid of the L-N-MePhe and the hydroxyl function of the L-Ser. IB-01212 is highly cytotoxic to different tumor cell lines.

  DOI：

  10.1021/jo051600p

文献信息

• Structure–Cytotoxicity Relationships of Analogues of <i>N</i>¹⁴-Desacetoxytubulysin H
  作者：Dorin Toader、Fengjiang Wang、Lakshmaiah Gingipalli、Melissa Vasbinder、Mark Roth、Shenlan Mao、Michael Block、Jay Harper、Sambaiah Thota、Mei Su、Jianquo Ma、Vahe Bedian、Adeela Kamal

  DOI：10.1021/acs.jmedchem.6b01023

  日期：2016.12.8

  Herein we report structure-cytotoxicity relationships for analogues of N-14-desacetoxytubulyisn H 1. A novel synthetic approach toward 1 enabled the discovery of compounds with a range of activity. Calculated basicity of the N-terminus of tubulysins was shown to be a good predictor of cytotoxicity. The impact of structural modifications at the C-terminus of 1 upon cytotoxicity is also described. These findings will facilitate the development of new tubulysin analogues for the treatment of cancer.
• IB-01212, a New Cytotoxic Cyclodepsipeptide Isolated from the Marine Fungus <i>Clonostachys</i> sp. ESNA-A009
  作者：Luis J. Cruz、Marta Martínez Insua、Julia Pérez Baz、Martha Trujillo、Ricard A. Rodriguez-Mias、Eliandre Oliveira、Ernest Giralt、Fernando Albericio、Librada M. Cañedo

  DOI：10.1021/jo051600p

  日期：2006.4.1

  IB-01212, a new cytotoxic cyclodepsipeptide featuring C-2 symmetry, was isolated from the mycelium extract of Clonostachys sp. ESNA-A009. The amino acid sequence of the compound was determined by spectroscopy techniques. The absolute configuration of the amino acids was determined by a combination of the Marfey and menthol methods. The structure, which was confirmed by comparison of the analytical data for the natural product with a sample obtained by solid-phase peptide synthesis, was revealed to be a cyclic dimer formed by two chains of L-N,N-Me(2)Leu-L-Ser-L-N-MeLeu-L-N-MePhe bound by the two esters formed between the carboxylic acid of the L-N-MePhe and the hydroxyl function of the L-Ser. IB-01212 is highly cytotoxic to different tumor cell lines.