(2S,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanolide | 114469-39-5

• 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: (2S,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanolide
• 英文别名: 5(S)-benzyloxycarbonylamino-6-cyclohexyl-2(S)-isopropyl-4(S)-hexanolide；(2S,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-2-isopropyl-4-hexanolide；benzyl N-[(1S)-2-cyclohexyl-1-[(2S,4S)-5-oxo-4-propan-2-yloxolan-2-yl]ethyl]carbamate
• CAS: 114469-39-5
• 化学式: C₂₃H₃₃NO₄
• 分子量: 387.519
• InChiKey: WLCVCJSJDZFQNK-ACRUOGEOSA-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

• 作为反应物：
  描述：

  (2S,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanolide 在 丙二酸环(亚)异丙酯 、 正丁基锂 、 二异丙胺 作用下， 生成 (2R,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanolide
  参考文献：
  名称：

  二肽等排物。2.由常见的γ-内酯中间体合成羟乙烯二肽等排非对映异构体。肾素和HIV-1蛋白酶抑制剂过渡态模拟物的制备。

  摘要：

  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。

  DOI：

  10.1016/s0040-4020(01)81896-2
• 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 (2S,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

• Processes for the preparation of 5-amino-4-hydroxyvaleric acid
  申请人：Ciba-Geigy Corporation

  公开号：US04898977A1

  公开（公告）日：1990-02-06

  The invention relates to novel processes and intermediates for the preparation of 5-amino-4-hydroxyvaleric acid derivatives of the formula ##STR1## in which R.sup.1 represents hydrogen, optionally substituted alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl, aryl-lower alkyl or the radical of a natural amino acid, R.sup.2 represents hydrogen, optionally substituted alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl, aryl-lower alkyl, amino, hydroxy, mercapto, sulphinyl, sulphonyl or the radical of a natural amino acid, and R.sup.3 represents optionally substituted hydroxy or amino, by sigmatropic rearrangement of a suitable allyl ester, halolactonisation of the resulting .gamma.,.delta.-unsaturated acid or of a suitable derivative thereof, exchange of halogen for a nitrogen-containing nucleophile, opening of the lactone ring and freeing of the amino group. Compounds of the formula I are starting materials for the preparation of renin-inhibitors which have an anti-hypertensive action.

  该发明涉及一种用于制备5-氨基-4-羟基戊酸衍生物的新工艺和中间体，其化学式为：其中R.sup.1代表氢、可选择地取代的烷基、环烷基、环烷基-较低烷基、芳基、芳基-较低烷基或天然氨基酸的基团，R.sup.2代表氢、可选择地取代的烷基、环烷基、环烷基-较低烷基、芳基、芳基-较低烷基、氨基、羟基、巯基、亚砜基、磺酰基或天然氨基酸的基团，R.sup.3代表可选择地取代的羟基或氨基，通过适当烯丙基酯的重排、所得γ、δ-不饱和酸的卤内酯化或其适当衍生物的卤素与含氮亲核试剂的交换、环内酯开环和氨基的释放。化合物I的起始物质用于制备具有抗高血压作用的肾素抑制剂。
• Isomerically pure 2-piperidone compounds
  申请人：Abbott Laboratories

  公开号：US05229518A1

  公开（公告）日：1993-07-20

  The present invention relates to intermediates useful in the process for the preparation of a compound of the formula: ##STR1## wherein R.sub.2a is hydrogen or loweralkyl, R.sub.2b is hydrogen, loweralkyl, cycloalkyl or phenyl and R.sub.1 is loweralkyl, cycloalky, cycloalkylalkyl, phenyl or benzyl. These intermediates are compounds of the formula: ##STR2## wherein R.sub.1, R.sub.2a and R.sub.2b are defined as above.

  本发明涉及在制备式化合物的过程中有用的中间体：##STR1## 其中，R.sub.2a是氢或较低的烷基，R.sub.2b是氢、较低的烷基、环烷基或苯基，而R.sub.1是较低的烷基、环烷基、环烷基烷基、苯基或苄基。这些中间体是式化合物：##STR2## 其中，R.sub.1，R.sub.2a和R.sub.2b如上所定义。
• Substantially isomerically pure hexane or hexene compounds
  申请人：Abbott Laboratories

  公开号：US05342981A1

  公开（公告）日：1994-08-30

  The present invention relates to intermediates useful in a process for the preparation of a compound of the formula: ##STR1## wherein R.sub.2a is hydrogen or loweralkyl, R.sub.2b is hydrogen, loweralkyl, cycloalkyl or phenyl and R.sub.1 is cycloalkyl, cycloalkylalkyl, phenyl or benzyl. These intermediates are compounds of the formula: ##STR2## wherein P.sub.2 is an O-protecting group, P.sub.3 is an N-protecting group and R.sub.1, R.sub.2a and R.sub.2b are defined as above.

  本发明涉及在制备以下化合物的过程中有用的中间体：##STR1## 其中R.sub.2a为氢或较低烷基，R.sub.2b为氢、较低烷基、环烷基或苯基，R.sub.1为环烷基、环烷基烷基、苯基或苄基。这些中间体是以下化合物：##STR2## 其中P.sub.2是O-保护基，P.sub.3是N-保护基，R.sub.1、R.sub.2a和R.sub.2b如上所定义。
• Verfahren zur Herstellung von 5-Amino-4-hydroxyvaleriansäure-Derivaten
  申请人：CIBA-GEIGY AG

  公开号：EP0258183B1

  公开（公告）日：1993-03-17
• US4898977A
  申请人：——

  公开号：US4898977A

  公开（公告）日：1990-02-06