(S)-5-benzyl-4-(4-methoxybenzyl)morpholin-3-one | 169297-81-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-5-benzyl-4-(4-methoxybenzyl)morpholin-3-one
• 英文别名: (5S)-5-benzyl-4-[(4-methoxyphenyl)methyl]morpholin-3-one
• CAS: 169297-81-8
• 化学式: C₁₉H₂₁NO₃
• 分子量: 311.381
• InChiKey: AZYHICWTRXOGQX-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-5-benzyl-4-(4-methoxybenzyl)morpholin-3-one 在 三氟乙酸 、 sodium iodide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙基苯 、 丙酮 、 正戊烷 为溶剂， 反应 13.0h， 生成
  参考文献：
  名称：

  Novel and Efficient Synthesis of Spirocyclic Morpholinones as Precursors of ψ[CH2O] Dipeptide Isosteres

  摘要：

  DOI：

  10.1055/s-1999-6050
• 作为产物：
  描述：

  L-苯丙氨醇 在 potassium tert-butylate 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.75h， 生成 (S)-5-benzyl-4-(4-methoxybenzyl)morpholin-3-one
  参考文献：
  名称：

  Novel and Efficient Synthesis of Spirocyclic Morpholinones as Precursors of ψ[CH2O] Dipeptide Isosteres

  摘要：

  DOI：

  10.1055/s-1999-6050

文献信息

• New, potent P1/P2-morpholinone-based HIV-protease inhibitors
  作者：Wieslaw M. Kazmierski、Eric Furfine、Andrew Spaltenstein、Lois L. Wright

  DOI：10.1016/j.bmcl.2006.07.014

  日期：2006.10

  morpholinone-based cyclic mimetics of the P1/P2 portion of the HIV-1 protease inhibitor Amprenavir. This effort led to discovery of allyl- and spiro-cyclopropyl-P2-substituted inhibitors 17 and 31, both 500 times more potent than the parent inhibitor 1. These results support morpholinones as novel mimetics of the P1/P2 portion of Amprenavir and potentially of other HIV-protease inhibitors, and thus provide

  我们已经开发了HIV-1蛋白酶抑制剂Amprenavir的P1 / P2部分基于吗啉酮的环状模拟物的有效合成。这项工作导致发现了烯丙基-和螺环丙基-P2-取代的抑制剂17和31，两者的活性都比母体抑制剂1高500倍。这些结果支持吗啉酮作为Amprenavir P1 / P2部分的新型模拟物，并可能其他HIV蛋白酶抑制剂，因此提供了一种新颖的药物化学模板，可优化针对更有效和类似药物的抑制剂。
• Stereoselective synthesis of novel methylene ether dipeptide isosteres
  作者：Bryan H. Norman、Julian S. Kroin

  DOI：10.1016/0040-4039(95)00712-l

  日期：1995.6

  We have developed a versatile new synthesis of the Ψ[CH2O] pseudopeptides from N-protected 5-substituted morpholin-3-ones. This approach focuses on a stereoselective alkylation of the morpholin-3-ones. The resulting alkylation products were used in the synthesis of some previously unavailable Ψ[CH2O] dipeptides.

  我们已经开发了一种由N保护的5-取代的吗啉-3-酮合成Ψ[CH 2 O]假肽的通用新方法。该方法集中于吗啉-3-酮的立体选择性烷基化。所得的烷基化产物用于合成某些先前无法获得的Ψ[CH 2 O]二肽。
• Alkylation Studies of <i>N</i>-Protected-5-substituted Morpholin-3-ones. A Stereoselective Approach to Novel Methylene Ether Dipeptide Isosteres
  作者：Bryan H. Norman、Julian S. Kroin

  DOI：10.1021/jo960496w

  日期：1996.1.1

  We have developed a versatile new synthesis of the Psi[CH2O] pseudopeptides from N-protected-5-substituted morpholin-3-ones. The morpholin-3-ones are prepared in two steps from the corresponding amino alcohols by treatment with ethyl chloroacetate, followed by protection of the amide, We found that direct alkylation of the protected morpholin-3-ones gives the expected alkylation product where the electrophile approaches from the face opposite to the existing side chain (derived from the amino alcohol). If an S amino alcohol is used, this procedure results in the formation of the (SE) Psi[CH2O] dipeptide. Alternatively, the (S,S) Psi[CH2O] dipeptide can be obtained if the protected morpholin-3-one enolate is quenched with an aldehyde and the aldol product is dehydrated and reduced. We have explored an alkylation/deprotonation/kinetic protonation scheme which is also amenable to the preparation of (S,S) pseudodipetides. It is, of course, possible to obtain the corresponding (R,R) and (S,R) Psi[CH2O] dipeptides by simply selecting the appropriate amino alcohols and reaction conditions. Finally, we have established that this method is general and can be applied to the preparation of numerous Psi[CH2O] dipeptides which were previously unavailable by existing methods.