4(S)-<(tert-butyloxycarbonyl)amino>-3-hydroxy-6-methyl-1-heptene | 187532-13-4

• 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: 4(S)-<(tert-butyloxycarbonyl)amino>-3-hydroxy-6-methyl-1-heptene
• 英文别名: (4S)-4-<(tert-butyloxycarbonyl)amino>-6-methyl-1-hepten-3-ol；(3RS,4S)-4-<(tert-Butoxycarbonyl)amino>-6-methyl-1-hepten-3-ol；tert-butyl ((4S)-3-hydroxy-6-methylhept-1-en-4-yl)carbamate；(3RS,4S)-4-t-Butyloxycarbonylamino-3-hydroxy-6-methylhept-1-ene；(3RS,4S)-4-(tert-butoxycarbonyl)amino-6-methylhepten-3-ol；tert-butyl N-[(4S)-3-hydroxy-6-methylhept-1-en-4-yl]carbamate
• CAS: 187532-13-4
• 化学式: C₁₃H₂₅NO₃
• 分子量: 243.346
• InChiKey: HFORXYBQJVPDTQ-VUWPPUDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4(S)-<(tert-butyloxycarbonyl)amino>-3-hydroxy-6-methyl-1-heptene 在 sodium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 双氧水 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 (4S,5S)-4-异丁基-5-(2-羟乙基)恶唑烷-2-酮
  参考文献：
  名称：

  Renin inhibitors. Dipeptide analogs of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond

  摘要：

  A series of dipeptide analogues of angiotensinogen have been prepared and evaluated for their ability to inhibit the aspartic proteinase renin. The compounds were derived from the renin substrate by replacing the scissile amide bond with a transition-state mimic and by incorporating bioisosteric replacements for the Val-10 amide bond. Analogue 21a exhibited an IC50 of 7.6 nM against purified human renin, showed high specificity for this enzyme, and produced a hypotensive response in anesthetized, salt-depleted cynomolgus monkeys.

  DOI：

  10.1021/jm00393a008
• 作为产物：
  描述：

  N-叔丁氧羰基-L-亮氨醇 在 草酰氯 、 二甲基亚砜 、 N,N-二异丙基乙胺 、 zinc(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 4(S)-<(tert-butyloxycarbonyl)amino>-3-hydroxy-6-methyl-1-heptene
  参考文献：
  名称：

  A Thermodynamic Preference of Chiral N-Methanesulfonyl and N-Arenesulfonyl 2,3-cis-3-Alkyl-2-Vinylaziridines over Their 2,3-Trans-Isomers:  Useful Palladium(0)-Catalyzed Equilibration Reactions for the Synthesis of (E)-Alkene Dipeptide Isosteres

  摘要：

  Palladium(0)-catalyzed reactions of N-methanesulfonyl- or N-(arenesulfonyl)-3-alkyl-2-vinylaziridines reveal that 2,3-cis-isomers are more stable than the corresponding 2,3-trans-isomers in accord with ab initio calculations. A highly stereoselective synthetic route to (E)-alkene dipeptide isosteres having desired stereochemistries from 2,3-cis-3-isobutyl-2-vinylaziridine by the use of organocopper chemistry is also presented.

  DOI：

  10.1021/jo961760o

文献信息

• Synthesis and Biological Activity of Peptide α-Ketoamide Derivatives as Proteasome Inhibitors
  作者：Salvatore Pacifico、Valeria Ferretti、Valentina Albanese、Anna Fantinati、Eleonora Gallerani、Francesco Nicoli、Riccardo Gavioli、Francesco Zamberlan、Delia Preti、Mauro Marastoni

  DOI：10.1021/acsmedchemlett.9b00233

  日期：2019.7.11

  Proteasome activity affects cell cycle progression as well as the immune response, and it is largely recognized as an attractive pharmacological target for potential therapies against several diseases. Herein we present the synthesis of a series of pseudodi/tripeptides bearing at the C-terminal position different α-ketoamide moieties as pharmacophoric units for the interaction with the catalytic threonine

  蛋白酶体活性影响细胞周期进程以及免疫应答，并且它被广泛认为是针对几种疾病的潜在疗法的有吸引力的药理学靶标。在本文中，我们提出了在C末端位置带有不同α-酮酰胺部分的一系列假二/三肽的合成，作为药效学单元，用于与维持蛋白酶体蛋白水解作用的苏氨酸残基相互作用。其中，我们确定了1-萘基衍生物13c是20S蛋白酶体β5亚基的有效和选择性抑制剂，在体外表现出纳摩尔效价（β5IC 50 = 7 nM，β1IC 50 = 60μM，β2IC 50> 100μM）。此外，它显着抑制人结肠直肠癌细胞系HCT116的增殖并诱导其凋亡。
• N-acylamino acid derivatives and their pharmaceutical compositions
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US05122523A1

  公开（公告）日：1992-06-16

  An N-acylamino acid derivative of the formula: ##STR1## wherein the substituents are herein defined or a salt thereof, which is useful as hypotensive drugs.

  一种公式为：##STR1## 的N-酰氨基酸衍生物，其中取代基如此定义或其盐，可用作降压药物。
• Functionalized peptidylaminoalcohols
  申请人：Abbott Laboratories

  公开号：US04725583A1

  公开（公告）日：1988-02-16

  The invention relates to renin inhibiting compounds of the formula ##STR1## wherein A is an N-protecting group; R.sub.1, R.sub.2 and R.sub.3 are independently selected from loweralkyl or lipophilic or aromatic amino acid side chains; and R.sub.4 is --CHO, --CO.sub.2 H, halomethyl or alkanoyl; and R.sub.5 is hydrogen or loweralkyl.

  该发明涉及公式为##STR1##的抑制肾素化合物，其中A是N-保护基团；R.sub.1、R.sub.2和R.sub.3分别选自低烷基或疏水性或芳香族氨基酸侧链；R.sub.4为--CHO、--CO.sub.2 H、卤代甲基或烷酰基；R.sub.5为氢或低烷基。
• 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。
• Amide bond surrogates: A general synthetic route to trans carbon-carbon double bono isosteres.
  作者：Youe-Kong Shue、George M. Carrera、Alex M. Nadzan

  DOI：10.1016/s0040-4039(00)95477-7

  日期：1987.1

  A practical synthesis toward trans double bond replacements of amide bond pseudo-peptides has been accomplished. This methodology provides a general route to a wide range of modified peptide analogs which may have biological significance.

  已经完成了对酰胺键伪肽的反式双键置换的实用合成。该方法学提供了获得广泛的修饰的肽类似物的一般途径，这些修饰的肽类似物可能具有生物学意义。