4-甲基-2-(S)-[(三苯基甲基)氨基]-1-戊醇 | 100841-17-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: 4-甲基-2-(S)-[(三苯基甲基)氨基]-1-戊醇
• 英文名称: N-tritylleucinol
• 英文别名: (2S)-4-methyl-2-(tritylamino)pentan-1-ol
• CAS: 100841-17-6
• 化学式: C₂₅H₂₉NO
• 分子量: 359.511
• InChiKey: DTDJODDDERHVIY-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-甲基-2-(S)-[(三苯基甲基)氨基]-1-戊醇 在 palladium dihydroxide sodium hydroxide 、 sodium periodate 、 草酰氯 、 DOWEX-50-X₈ 、 氢气 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 35.58h， 生成 (7R)-7-isobutylperhydroazepin-2-one
  参考文献：
  名称：

  Evans, P. Andrew; Holmes, Andrew B.; Russell, Keith, Journal of the Chemical Society. Perkin transactions I, 1994, # 23, p. 3397 - 3410

  摘要：

  DOI：
• 作为产物：
  描述：

  methyl N-tritylleucinate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 4-甲基-2-(S)-[(三苯基甲基)氨基]-1-戊醇
  参考文献：
  名称：

  New inhibitors of renin that contain novel phosphostatine Leu-Val replacements

  摘要：

  A novel series of renin inhibitors based on the Phe8-His9-Leu10-Val11 substructure of renin's natural substrate, angiotensinogen, is reported. These inhibitors retain the Phe8-His9 portion of the native substructure and employ novel phosphostatine Leu10-Val11 replacements (LVRs). The phosphostatine LVRs were prepared by condensing a dialkyl phosphonate ester stabilized anion with either N-t-Boc-amino aldehydes or N-tritylamino aldehydes (derived from the corresponding amino acid). Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine. The dialkyl ester moiety was varied and a loss in potency was incurred when the alkyl ester was chain extended or alpha-branched; dimethyl esters provided optimum potency. The phosphonate moiety was replaced by a half-acid half-ester phosphonate and dimethylphosphinate; both replacements lead to a loss in potency. The more potent inhibitors (IC50 = 20-50 nM) were found to be selective inhibitors for renin over porcine pepsin and bovine cathepsin D (little or no inhibition was observed at 10(-5) M).

  DOI：

  10.1021/jm00164a011

文献信息

• Hydrogen‐Borrowing Alkylation of 1,2‐Amino Alcohols in the Synthesis of Enantioenriched γ‐Aminobutyric Acids
  作者：Christopher J. J. Hall、William R. F. Goundry、Timothy J. Donohoe

  DOI：10.1002/anie.202100922

  日期：2021.3.22

  For the first time we have been able to employ enantiopure 1,2‐amino alcohols derived from abundant amino acids in C−C bond‐forming hydrogen‐borrowing alkylation reactions. These reactions are facilitated by the use of the aryl ketone Ph*COMe. Racemisation of the amine stereocentre during alkylation can be prevented by the use of sub‐stoichiometric base and protection of the nitrogen with a sterically

  我们首次能够在 C-C 键形成借氢烷基化反应中使用源自丰富氨基酸的对映体纯 1,2-氨基醇。使用芳基酮 Ph*COMe 可以促进这些反应。通过使用亚化学计量的碱并用位阻三苯甲烷（三苯甲基）或苄基保护氮，可以防止烷基化过程中胺立构中心的外消旋化。 Ph* 和三苯甲基在一锅中即可轻松裂解，得到 γ-氨基丁酸 (GABA) 盐酸盐产品，无需进一步纯化。这两个步骤可以依次进行，无需分离借氢中间体，从而无需柱色谱法。
• Renin inhibitors. Design of angiotensinogen transition-state analogs containing novel (2R,3R,4R,5S)-5-amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic acid
  作者：Suvit Thaisrivongs、Donald T. Pals、Lisa T. Kroll、Steve R. Turner、Fu Son Han

  DOI：10.1021/jm00389a004

  日期：1987.6

  5S)-5-amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic acid residue at the scissile site are shown to be potent inhibitors of human plasma renin. The glycol moiety in this novel acid, dihydroxyethylene isostere, is suggested to act as a transition-state analogue and mimics the tetrahedral intermediate formed during the enzyme-catalyzed hydrolysis of the peptidic bond.

  2（R）-[5（R）-[1（S）-[（叔丁氧羰基氨基）氨基] -3-甲基丁基] -2,2-二甲基-4（R-二氧戊环）-的高立体选择性合成描述了3-甲基丁酸。这是一种适当保护的羧酸，可用作制备肾素抑制肽的中间体。血管紧张素原类似物如肽IX和X在易裂位点含有二肽等排物（2R，3R，4R，5S）-5-氨基-3,4-二羟基-2-异丙基-7-甲基辛酸残基人血浆肾素的有效抑制剂。该新型酸二羟基乙烯等排物中的二醇部分被建议充当过渡态类似物，并模仿在酶催化的肽键水解过程中形成的四面体中间体。
• Novel renin inhibiting peptides having a dihydroxyethylene isostere transition state insert
  申请人：THE UPJOHN COMPANY

  公开号：EP0237202A2

  公开（公告）日：1987-09-16

  The present invention provides novel renin-inhibiting peptides of the formula X-A6-B7-C8-D9-E10-F11-G12-H13-I14-Z, wherein the E10-F11 moiety is a dihydroxyethylene isostere, X and Z are terminal groups, and the remaining variables are absent or are amino acid residues. Such inhibitors are useful for the control of hypertension.

  本发明提供了式X-A6-B7-C8-D9-E10-F11-G12-H13-I14-Z的新型肾素抑制肽，其中E10-F11分子是二羟基乙烯异构体，X和Z是末端基团，其余变量不存在或为氨基酸残基。 这种抑制剂可用于控制高血压。
• Liquid detergents containing a peptide trifluoromethyl ketone
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0583535A1

  公开（公告）日：1994-02-23

  Aqueous liquid detergent compositions are described which comprise a proteolytic enzyme wherein the proteolytic activity is reversibly inhibited by a peptide trifluoromethyl ketone.

  所述的水基液体洗涤剂组合物包含一种蛋白水解酶，其中蛋白水解酶的活性被一种肽三氟甲基酮可逆地抑制。
• New inhibitors of renin that contain novel phosphostatine Leu-Val replacements
  作者：Joseph F. Dellaria、Robert G. Maki、Herman H. Stein、Jerome Cohen、David Whittern、Kennan Marsh、Daniel J. Hoffman、Jacob J. Plattner、Thomas J. Perun

  DOI：10.1021/jm00164a011

  日期：1990.2

  A novel series of renin inhibitors based on the Phe8-His9-Leu10-Val11 substructure of renin's natural substrate, angiotensinogen, is reported. These inhibitors retain the Phe8-His9 portion of the native substructure and employ novel phosphostatine Leu10-Val11 replacements (LVRs). The phosphostatine LVRs were prepared by condensing a dialkyl phosphonate ester stabilized anion with either N-t-Boc-amino aldehydes or N-tritylamino aldehydes (derived from the corresponding amino acid). Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine. The dialkyl ester moiety was varied and a loss in potency was incurred when the alkyl ester was chain extended or alpha-branched; dimethyl esters provided optimum potency. The phosphonate moiety was replaced by a half-acid half-ester phosphonate and dimethylphosphinate; both replacements lead to a loss in potency. The more potent inhibitors (IC50 = 20-50 nM) were found to be selective inhibitors for renin over porcine pepsin and bovine cathepsin D (little or no inhibition was observed at 10(-5) M).