(2R,3S,4S)-3-hexyl-4-(2-hydroxy-hex-5-enyl)-oxetan-2-one | 1151391-89-7

• 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: (2R,3S,4S)-3-hexyl-4-(2-hydroxy-hex-5-enyl)-oxetan-2-one
• 英文别名: (3S,4S)-3-hexyl-4-[(2R)-2-hydroxyhex-5-enyl]oxetan-2-one
• CAS: 1151391-89-7
• 化学式: C₁₅H₂₆O₃
• 分子量: 254.37
• InChiKey: FGRMZDNDNMUTII-RDBSUJKOSA-N

物化性质

• 沸点：
  382.8±15.0 °C(predicted)
• 密度：
  0.983±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  (2R,3S,4S)-3-hexyl-4-(2-hydroxy-hex-5-enyl)-oxetan-2-one 、 N-甲酰-L-苯丙氨酸 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以46%的产率得到(S)-2-formylamino-3-phenyl-propionic acid 1-((2S,3S,4S)-3-hexyl-4-oxo-oxetan-2-ylmethyl)-pent-4-enyl ester
  参考文献：
  名称：

  Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase

  摘要：

  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.

  DOI：

  10.1021/jm800321h
• 作为产物：
  描述：

  Tert-butyl-dimethyl-(1-pyridin-2-ylsulfanyloct-1-enoxy)silane 、 (R)-(+)-3-(tert-butyldimethylsiloxy)-6-heptenal 在 zinc(II) chloride 、 氢氟酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 60.0h， 生成 (2R,3S,4S)-3-hexyl-4-(2-hydroxy-hex-5-enyl)-oxetan-2-one 、
  参考文献：
  名称：

  Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase

  摘要：

  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.

  DOI：

  10.1021/jm800321h

文献信息

• BETA-LACTONE COMPOUNDS
  申请人：Smith Jeffrey W.

  公开号：US20090124681A1

  公开（公告）日：2009-05-14

  The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and R 1 comprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.

  本发明提供具有一般结构A的化合物，或其药学上可接受的衍生物：其中R是烷基基团，R1包括至少一种从烷基、烯基、芳基、杂环、羟基、酯、酰胺、醛基和卤素组成的基团。
• Oxetanones
  申请人：Hoffmann-La Roche Inc.

  公开号：US04931463A1

  公开（公告）日：1990-06-05

  Racemic compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and n are as described herein, enantiomers and diastereomers thereof, and salts of these esters with weak acids, are described. These compounds inhibit pancreas lipase and are useful agents in the treatment of obesity, hyperlipaemia, atherosclerosis and arteriosclerosis.

  描述了化学式为##STR1##的外消旋化合物，其中R.sup.1，R.sup.2，R.sup.3，R.sup.4，R.sup.5和n如本文所述，其对映异构体和非对映异构体以及这些酯的弱酸盐。这些化合物抑制胰脂酶，是治疗肥胖症，高脂血症，动脉粥样硬化和动脉硬化的有用药物。
• Beta-lactone compounds
  申请人：Burnham Institute for Medical Research

  公开号：US08258321B2

  公开（公告）日：2012-09-04

  The present invention provides compounds having the general structure A, or a pharmaceutically acceptable derivatives thereof: wherein R is an alkyl group, and R1 comprises at least one moiety selected from a group consisting of an alkyl, an alkenyl, an aryl, a heterocycle, hydroxyl, ester, amido, aldehyde, and a halogen.

  本发明提供具有一般结构A或其药学上可接受的衍生物的化合物：其中R为烷基，R1包括至少一种从烷基，烯基，芳基，杂环，羟基，酯，酰胺，醛和卤素组成的基团。
• 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