(3R,4R)-3-hexyl-4-<(R)-2'-hydroxytridecyl>-2-oxetanone | 104872-19-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (3R,4R)-3-hexyl-4-<(R)-2'-hydroxytridecyl>-2-oxetanone
• 英文别名: (3R,4R)-3-hexyl-4-((R)-2-hydroxytridecyl)-oxetan-2-one；(3R,4R)-3-hexyl-4-((R)-2-hydroxytridecyl)oxetan-2-one；(3R,4R)-3-hexyl-4-[(2R)-2-hydroxytridecyl]oxetan-2-one
• CAS: 104872-19-7
• 化学式: C₂₂H₄₂O₃
• 分子量: 354.574
• InChiKey: RSOUWOFYULUWNE-NJDAHSKKSA-N

物化性质

• 熔点：
  46-47 °C
• 沸点：
  467.9±18.0 °C(Predicted)
• 密度：
  0.935±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  25
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R,4R)-3-hexyl-4-<(R)-2'-hydroxytridecyl>-2-oxetanone 在 palladium 10% on activated carbon 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.58h， 生成
  参考文献：
  名称：

  Asymmetric Total Synthesis of ent-Tetrahydrolipstatin from an Epoxy Alkenol

  摘要：

  A highly efficient asymmetric total synthesis of ent-tetrahydrolipstatin (THL) was accomplished from the known epoxy alkenol. The beta-lactone portion of THL was synthesized by the epoxide opening with cyanide and stereoselective enolate alkylation method. The side chain was introduced by cross metathesis of the alkene part with 1-decene. Coupling with a protected leucine completed the synthesis of ent-tetrahydrolipstatin.

  DOI：

  10.1055/s-0031-1290407
• 作为产物：
  描述：

  3-氧代十四酸乙酯 在 氢氟酸 、 二异丁基氢化铝 、 zinc(II) chloride 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 67.0h， 生成 (3R,4R)-3-hexyl-4-<(R)-2'-hydroxytridecyl>-2-oxetanone
  参考文献：
  名称：

  Total Synthesis and Comparative Analysis of Orlistat, Valilactone, and a Transposed Orlistat Derivative:  Inhibitors of Fatty Acid Synthase

  摘要：

  Concise syntheses of orlistat ( Xenical), a two-carbon transposed orlistat derivative, and valilactone are described that employ the tandem Mukaiyama aldol-lactonization (TMAL) process as a key step. This process allows facile modification of the alpha-side chain. Versatile strategies for modifying the delta-side chain are described, involving cuprate addition and olefin metathesis. Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling.

  DOI：

  10.1021/ol061651o

文献信息

• An Asymmetric Synthesis of (-)-Tetrahydrolipstatin
  作者：Agnès Pommier、Jean-Marc Pons、Philip J. Kocienski、Loretta Wong

  DOI：10.1055/s-1994-25684

  日期：——

  A key step in a short asymmetric synthesis of the potent pancreatic lipase inhibitor (-)-tetrahydrolipstatin (2) is a Lewis acid-catalysed [2+2] cycloaddition of n-hexyl(trimethylsilyl)ketene (5) to (R) -3-(tert-butyldimethylsilyloxy)tetradecanal (4a).

  一种有效的胰脂肪酶抑制剂（-）-四氢脂肪酸酯（2）短链不对称合成中的关键步骤是n-己基（ trimethylsilyl）酮烯（5）与（R）-3-（叔丁基二甲基硅氧基）十四烷醛（4a）进行路易斯酸催化的[2+2]环加成反应。
• Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase
  作者：Robyn D. Richardson、Gil Ma、Yatsandra Oyola、Manuel Zancanella、Lynn M. Knowles、Piotr Cieplak、Daniel Romo、Jeffrey W. Smith

  DOI：10.1021/jm800321h

  日期：2008.9.11

  Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report oil the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and arnino ester substitutions were altered and tile resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display all increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings Support the idea that all orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.
• Oxetanone
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0185359B1

  公开（公告）日：1991-12-04
• US4931463A
  申请人：——

  公开号：US4931463A

  公开（公告）日：1990-06-05
• US5175186A
  申请人：——

  公开号：US5175186A

  公开（公告）日：1992-12-29