(2R,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanolide | 114469-40-8

• 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: (2R,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanolide
• 英文别名: benzyl N-[(1S)-2-cyclohexyl-1-[(2S,4R)-5-oxo-4-propan-2-yloxolan-2-yl]ethyl]carbamate
• CAS: 114469-40-8
• 化学式: C₂₃H₃₃NO₄
• 分子量: 387.519
• InChiKey: WLCVCJSJDZFQNK-HKBOAZHASA-N

物化性质

• 沸点：
  562.8±33.0 °C(predicted)
• 密度：
  1.099±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异戊酸甲酯 在 盐酸 、 正丁基锂 、 potassium tert-butylate 、 水 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 六甲基磷酰三胺 、 乙醚 为溶剂， 反应 20.5h， 生成 (2R,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanolide
  参考文献：
  名称：

  Synthesis and biological activity of some transition-state inhibitors of human renin

  摘要：

  A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu (OH)/Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (CHa /(OH)/Val) was prepared. A structure-activity study with Boc-Phe-His-Leu (OH)/Val-Ile-His-NH2 (8a) as starting material led to N-[(2S)-2-[(tert-butylsulfonyl)methyl]-3-phenylpropionyl]-His-Cha (OH)/ Val- NHC4H9-n (8i) which has the length of a tetrapeptide and contains only one natural amino acid. Compound 8i had an IC50 of 2 x 10(-9) M against human renin and showed high enzyme specificity; IC50 values against the related aspartic proteinases pepsin and cathepsin D were (8 x 10(-6) and 3 x 10(-6) M, respectively). In salt-depleted marmosets, 8i inhibited plasma renin activity PRA and lowered blood pressure for up to 2 h after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00117a027

文献信息

• Dipeptide isosteres. 2. Synthesis of hydroxyethylene dipeptide isostere diastereomers from a common γ-lactone intermediate. Preparation of renin and HIV-1 protease inhibitor transition state mimics.
  作者：William R. Baker、John K. Pratt

  DOI：10.1016/s0040-4020(01)81896-2

  日期：1993.1

  A general strategy for the synthesis of the hydroxyethylene dipeptide isostere diastereomers C or D has been developed. The syntheses proceeded through a common γ-lactone intermediate A or B. The C(3α) γ-lactone diastereomer A was prepared from the N-Cbz protected α-amino aldehyde and 2-(2-isopropylpropen-2-yl)trimethylsilane in five steps. The C(3β) γ-lactone diastereomer B was obtained by kinetic

  已经开发了合成羟乙烯二肽等排非对映异构体C或D的一般策略。合成过程通过常见的γ-内酯中间体A或B进行。由N-Cbz保护的α-氨基醛和2-（2-异丙基丙烯-2-基）三甲基硅烷分五个步骤制备C（3α）γ-内酯非对映异构体A。C（3β）γ-内酯非对映异构体B是通过使用丙二酸酯衍生物对内酯烯醇酯进行动态质子化而获得的。
• US5091425A
  申请人：——

  公开号：US5091425A

  公开（公告）日：1992-02-25
• US5229518A
  申请人：——

  公开号：US5229518A

  公开（公告）日：1993-07-20
• US5342981A
  申请人：——

  公开号：US5342981A

  公开（公告）日：1994-08-30
• Synthesis and biological activity of some transition-state inhibitors of human renin
  作者：Peter Buehlmayer、Anthony Caselli、Walter Fuhrer、Richard Goeschke、Vittorio Rasetti、Heinrich Rueger、James L. Stanton、Leoluca Criscione、Jeanette M. Wood

  DOI：10.1021/jm00117a027

  日期：1988.9

  A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu (OH)/Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (CHa /(OH)/Val) was prepared. A structure-activity study with Boc-Phe-His-Leu (OH)/Val-Ile-His-NH2 (8a) as starting material led to N-[(2S)-2-[(tert-butylsulfonyl)methyl]-3-phenylpropionyl]-His-Cha (OH)/ Val- NHC4H9-n (8i) which has the length of a tetrapeptide and contains only one natural amino acid. Compound 8i had an IC50 of 2 x 10(-9) M against human renin and showed high enzyme specificity; IC50 values against the related aspartic proteinases pepsin and cathepsin D were (8 x 10(-6) and 3 x 10(-6) M, respectively). In salt-depleted marmosets, 8i inhibited plasma renin activity PRA and lowered blood pressure for up to 2 h after oral administration of a dose of 10 mg/kg.