tert-butyl (S)-1-((2S,4S)-4-(2-hydroxypropan-2-yl)-5-oxotetrahydrofuran-2-yl)-3-methylbutylcarbamate | 125015-97-6

• 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: tert-butyl (S)-1-((2S,4S)-4-(2-hydroxypropan-2-yl)-5-oxotetrahydrofuran-2-yl)-3-methylbutylcarbamate
• 英文别名: (3S, 5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-3-methylbutyl]-3-(1-hydroxy-1-methylethyl)dihydrofuran-2(3H)-one；tert-butyl N-[(1S)-1-[(2S,4S)-4-(2-hydroxypropan-2-yl)-5-oxooxolan-2-yl]-3-methylbutyl]carbamate
• CAS: 125015-97-6
• 化学式: C₁₇H₃₁NO₅
• 分子量: 329.437
• InChiKey: HYRGFEPWZWLDSZ-AGIUHOORSA-N

物化性质

• 熔点：
  95-97 °C(Solvent: Diethyl ether; Hexane)
• 沸点：
  477.1±10.0 °C(predicted)
• 密度：
  1.084±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-1-((2S,4S)-4-(2-hydroxypropan-2-yl)-5-oxotetrahydrofuran-2-yl)-3-methylbutylcarbamate 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三苯基氢化锡 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.33h， 生成 (2R,4S,5S)-2-(2-propyl)-4-hydroxy-5-<(tert-butyloxycarbonyl)amino>-7-methyloctanoic acid δ-lactone
  参考文献：
  名称：

  On a Possible Neutral Charge State for the Catalytic Dyad in β-Secretase When Bound to Hydroxyethylene Transition State Analogue Inhibitors

  摘要：

  beta-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients Our previous results using a combination of surface plasmon resonance experiments with molecular Modeling calculations: suggested that the Asp dyad in beta-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.

  DOI：

  10.1021/jm101568y
• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-4-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 Pd-BaSO₄ [(R)-BINAP]RuBr₂ 、 3 A molecular sieve 、 氢气 、 溶剂黄146 、 pyridinium chlorochromate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， -78.0~100.0 ℃ 、405.3 kPa 条件下， 生成 tert-butyl (S)-1-((2S,4S)-4-(2-hydroxypropan-2-yl)-5-oxotetrahydrofuran-2-yl)-3-methylbutylcarbamate
  参考文献：
  名称：

  Nishi, Takahide; Kataoka, Mitsuru; Morisawa, Yasuhiro, Chemistry Letters, 1989, p. 1993 - 1996

  摘要：

  DOI：

文献信息

• Renin-inhibitory oligopeptides, their preparation and use
  申请人：Sankyo Company, Limited

  公开号：US05364844A1

  公开（公告）日：1994-11-15

  Compounds of formula (I): ##STR1## A is a carbon-carbon bond or C.sub.1 -C.sub.3 alkylene; B is imino group or C.sub.1 -C.sub.2 alkylene; R.sup.1 is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, heterocyclic or optionally substituted amino; R.sup.2 is optionally substituted phenyl or optionally substituted naphthyl; R.sup.3 is thiazolyl, isoxazolyl or imidazolyl; R.sup.4 is isopropyl or cyclohexyl; R.sup.5 and R.sup.6 are C.sub.1 -C.sub.4 alkyl, or, together with the carbon atom to which they are attached, C.sub.3 -C.sub.7 cycloalkyl; R.sup.7 is hydrogen, optionally substituted C.sub.1 -C.sub.6 alkyl group; and R.sup.8 is hydrogen or C.sub.1 -C.sub.4 alkyl. These compounds have renin-inhibitory and, hence, hypotensive activities. The invention also provides a method for the treatment or prophylaxis of hypertension induced by failures in the renin-angiotensin system.

  化合物的式子(I): ##STR1## A是碳-碳键或C.sub.1-C.sub.3烷基; B是亚胺基或C.sub.1-C.sub.2烷基; R.sup.1是C.sub.1-C.sub.4烷基，C.sub.1-C.sub.4烷氧基，杂环或可选择取代的氨基; R.sup.2是可选择取代的苯基或可选择取代的萘基; R.sup.3是噻唑基，异恶唑基或咪唑基; R.sup.4是异丙基或环己基; R.sup.5和R.sup.6是C.sub.1-C.sub.4烷基，或与它们连接的碳原子一起，C.sub.3-C.sub.7环烷基; R.sup.7是氢，可选择取代的C.sub.1-C.sub.6烷基; R.sup.8是氢或C.sub.1-C.sub.4烷基。这些化合物具有肾素抑制和因此降压的活性。该发明还提供了一种治疗或预防由于肾素-血管紧张素系统失调引起的高血压的方法。
• NISHI, TAKAHIDE;KATAOKA, MITSURU;MORISAWA, YASUHIRO, CHEM. LETT.,(1989) N1, C. 1993-1996
  作者：NISHI, TAKAHIDE、KATAOKA, MITSURU、MORISAWA, YASUHIRO

  DOI：——

  日期：——
• Nishi, Takahide; Kataoka, Mitsuru; Morisawa, Yasuhiro, Chemistry Letters, 1989, p. 1993 - 1996
  作者：Nishi, Takahide、Kataoka, Mitsuru、Morisawa, Yasuhiro

  DOI：——

  日期：——
• On a Possible Neutral Charge State for the Catalytic Dyad in β-Secretase When Bound to Hydroxyethylene Transition State Analogue Inhibitors
  作者：Fredy Sussman、José M. Otero、M. Carmen Villaverde、Marian Castro、José L. Domínguez、Lucía González-Louro、Ramón J. Estévez、J. Carlos Estévez

  DOI：10.1021/jm101568y

  日期：2011.4.28

  beta-Secretase is one of the aspartic proteases involved in the formation of amyloid plaques in Alzheimer's disease patients Our previous results using a combination of surface plasmon resonance experiments with molecular Modeling calculations: suggested that the Asp dyad in beta-secretase bound to hydroxylethylene containing inhibitors adopts a neutral charged state. In this work, we show that the Asp dyad diprotonated state reproduced the binding ranking of a set of these inhibitors better than alternative protonation states.