5(R)-bromo-6-cyclohexyl-2(S)-isopropyl-4(S)-hexanolide | 118041-14-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 5(R)-bromo-6-cyclohexyl-2(S)-isopropyl-4(S)-hexanolide
• 英文别名: (3S,5S)-5-[(1R)-1-bromo-2-cyclohexylethyl]-3-propan-2-yloxolan-2-one
• CAS: 118041-14-8
• 化学式: C₁₅H₂₅BrO₂
• 分子量: 317.266
• InChiKey: UQPZOIWSMAFISO-MJBXVCDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5(R)-bromo-6-cyclohexyl-2(S)-isopropyl-4(S)-hexanolide 在 palladium on activated charcoal sodium azide 、 氢气 作用下， 以 乙醇 为溶剂， 生成 <3S-<3α,5β(R^*)>>-5-(2-Cyclohexyl-1-aminoethyl)dihydro-3-isopropyl-2(3H)-furanone
  参考文献：
  名称：

  使用手性酰基恶唑烷酮的立体选择性溴内酯化有效合成对应于羟乙烯二肽等排物的γ-内酯

  摘要：

  一种有效的合成路线描述于γ内酯对应于二肽电子等排体（2 ，4 ，5 ）-5-氨基-6-环己基-4-羟基-2-异丙基己酸，其中立体化学控制是通过参与实现立体选择性溴内酯化反应中的手性酰基恶唑烷酮。

  DOI：

  10.1016/s0040-4039(01)80674-2
• 作为产物：
  描述：

  N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-3-N-dimethylbutyramide 在 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 溶剂黄146 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 水 为溶剂， 反应 14.25h， 生成 5(R)-bromo-6-cyclohexyl-2(S)-isopropyl-4(S)-hexanolide
  参考文献：
  名称：

  Formal, Stereoselective Synthesis of Hydroxyethylene Dipeptide Isosteres Utilizing Pseudoephedrine Amides

  摘要：

  DOI：

  10.1021/jo9707951

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

  公开号：US05010189A1

  公开（公告）日：1991-04-23

  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, halolactonization 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.

  本发明涉及一种制备5-氨基-4-羟基戊酸衍生物的新型方法和中间体，其化学式为##STR1##其中R.sup.1表示氢，可选择性地取代烷基，环烷基，环烷基-低烷基，芳基，芳基-低烷基或天然氨基酸的基团，R.sup.2表示氢，可选择性地取代烷基，环烷基，环烷基-低烷基，芳基，芳基-低烷基，氨基，羟基，硫醇基，亚磺酰基或天然氨基酸的基团，R.sup.3表示可选择性地取代的羟基或氨基，通过适当的烯丙酸酯的sigma-转位，γ，δ-不饱和酸或其适当衍生物的卤代内酯化，卤素与含氮亲核试剂的交换，开环内酯环并释放氨基的方法制备。化合物I的式是制备抑制肾素的起始材料，具有降压作用。
• Verfahren zur Herstellung von 5-Amino-4-hydroxyvaleriansäure-Derivaten
  申请人：CIBA-GEIGY AG

  公开号：EP0258183A2

  公开（公告）日：1988-03-02

  Die Erfindung betrifft neue Verfahren und Zwischenprodukte zur Herstellung von 5-Amino-4-hydroxyvaleriansäure-Derivaten der Formel worin R¹ Wasserstoff, gegebenenfalls substituiertes Alkyl, Cyclo­alkyl, Cycloalkylniederalkyl, Aryl, Arylniederalkyl oder den Rest einer natürlichen Aminosäure, R² Wasserstoff, gegebenenfalls substituiertes Alkyl, Cycloalkyl, Cycloalkylniederalkyl, Aryl, Arylniederalkyl, Amino, Hydroxy, Mercapto, Sulfinyl, Sulfonyl oder den Rest einer natürlichen Aminosäure und R³ gegebenenfalls substi­tuiertes Hydroxy oder Amino darstellen, durch sigmatrope Umlagerung eines geeigneten Allylesters, Halolactonisierung der erhältlichen γ,δ-ungesättigten Säure oder eines geeigneten Derivats davon, Aus­tausch von Halogen durch ein stickstoffhaltiges Nukleophil, Lacton­ringöffnung und Freisetzung der Aminogruppe. Verbindungen der Formel I sind Ausgangsstoffe zur Herstellung von anti-hypertensiv wirksamen Reninhemmern.

  本发明涉及制备 5-氨基-4-羟基戊酸衍生物的新工艺和中间体，其式如下 其中 R¹ 是氢、任选取代的烷基、环烷基、环烷基-低级烷基、芳基、芳基-低级烷基或天然氨基酸的基，R² 是氢、任选取代的烷基、环烷基、环烷基-低级烷基、芳基、芳基-低级烷基、氨基、羟基、巯基、亚砜基、磺酰基或天然氨基酸的基，R³ 是任选取代的羟基或天然氨基酸的基、磺酰基或天然氨基酸的残基且 R³ 任选为取代的羟基或氨基，通过合适的烯丙基酯的西格玛重排、可获得的 γ，δ-不饱和酸或其合适衍生物的卤代内酯化、含氮亲核物取代卤素、内酯开环和释放氨基。式 I 化合物是制备抗高血压肾素抑制剂的起始原料。
• 1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 2. Synthesis, biological properties and molecular modeling of hydroxyethylene isostere derivatives
  作者：Robert H. Bradbury、John S. Major、Alec A. Oldham、Janet E. Rivett、David A. Roberts、Anthony M. Slater、David Timms、David Waterson

  DOI：10.1021/jm00171a006

  日期：1990.9

  A series of inhibitors of human renin have been synthesized, derived from combination of a 2-(8-propyl-6-pyridin-3-yl-1,2,4-triazolo[4,3-a]pyrazin-3-yl)- 3-pyridin- 3-ylpropionic acid moiety 6c with the hydroxyethylene isostere of the scissile amide bond (2S,4S,5S)-5-amino-6-cyclohexyl-4-hydroxy-2-isopropylhexanoic acid (ChaOH--Val). The more potent members of this series showed good inhibitory activity against partially purified human renin, 7d, for example, having an IC50 of 0.2 nM. Structure-activity relationships for these compounds were consistent with their binding to the S4-S2' sites of human renin. Analogues 7e and 7h-k with a variety of substituents at the C-terminus all had in vitro IC50S less than 1 nM. In contrast with the majority of previously reported inhibitors of similar potency, these compounds contain no natural amino acid fragments. When administered intravenously to anesthetized, sodium-depleted marmosets at doses of 0.3-3.0 mg/kg, compound 7d caused a marked reduction in mean arterial pressure. Following oral administration at 30 mg/kg in the same animal model, 7d again elicited a significant fall in mean arterial pressure, accompanied by suppression of plasma renin activity lasting up to 3 h after dosing.
• A versatile and stereocontrolled synthesis of hydroxyethylene dipeptide isosteres
  作者：Peter Herold、Rudolph Duthaler、Grety Rihs、Christof Angst

  DOI：10.1021/jo00266a034

  日期：1989.3