(3aR,4R,5R,6aS)-Hexahydro-4-<(E)-(3R)-4-phenoxy-3-<(tetrahydro-2H-pyran-2-yl)oxy>-1-butenyl>-5-<(tetrahydro-2H-pyran-2-yl)oxy>-2H-cyclopentafuran-2-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3aR,4R,5R,6aS)-Hexahydro-4-<(E)-(3R)-4-phenoxy-3-<(tetrahydro-2H-pyran-2-yl)oxy>-1-butenyl>-5-<(tetrahydro-2H-pyran-2-yl)oxy>-2H-cyclopentafuran-2-one
• 英文别名: (3aR,4R,5R,6aS)-5-(oxan-2-yloxy)-4-[(E,3R)-3-(oxan-2-yloxy)-4-phenoxybut-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one
• 化学式: C₂₇H₃₆O₇
• 分子量: 472.579
• InChiKey: OQIINYYSXYDPEA-CADBMRNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3aR,4R,5R,6aS)-Hexahydro-4-<(E)-(3R)-4-phenoxy-3-<(tetrahydro-2H-pyran-2-yl)oxy>-1-butenyl>-5-<(tetrahydro-2H-pyran-2-yl)oxy>-2H-cyclopentafuran-2-one 在 jones reagent 、 sodium methylsulfinylcarbanide 、 二异丁基氢化铝 、 溶剂黄146 作用下， 以 正己烷 、 丙酮 、 甲苯 为溶剂， 反应 16.41h， 生成 硫前列酮
  参考文献：
  名称：

  N-(Methanesulfonyl)-16-phenoxyprostaglandin carboxamides: tissue-selective, uterine stimulants

  摘要：

  In an effort to develop tissue-selective prostaglandin analogues resistant to the metabolic inactivating pathways of the natural materials, hybrid compounds modified both at C-1 with a sulfonimide moiety and in the n-amylcarbinol side chain with substituted phenoxy groups were synthesized and evaluated in a variety of in vitro models. Several of these analogues exhibited potent, tissue-selective, uterine stimulant activity, a finding subsequently confirmed in clinical studies with one member of this series, N-(methanesulfonyl)-16-phenoxy-omega-tetranor-PGE2-carboxamide (CP-34089/ZK-57671, sulprostone).

  DOI：

  10.1021/jm00143a018
• 作为产物：
  描述：

  苯氧乙酸甲酯 在 sodium hydride 、 三乙基硼氢化锂 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 (3aR,4R,5R,6aS)-Hexahydro-4-<(E)-(3R)-4-phenoxy-3-<(tetrahydro-2H-pyran-2-yl)oxy>-1-butenyl>-5-<(tetrahydro-2H-pyran-2-yl)oxy>-2H-cyclopentafuran-2-one
  参考文献：
  名称：

  N-(Methanesulfonyl)-16-phenoxyprostaglandin carboxamides: tissue-selective, uterine stimulants

  摘要：

  In an effort to develop tissue-selective prostaglandin analogues resistant to the metabolic inactivating pathways of the natural materials, hybrid compounds modified both at C-1 with a sulfonimide moiety and in the n-amylcarbinol side chain with substituted phenoxy groups were synthesized and evaluated in a variety of in vitro models. Several of these analogues exhibited potent, tissue-selective, uterine stimulant activity, a finding subsequently confirmed in clinical studies with one member of this series, N-(methanesulfonyl)-16-phenoxy-omega-tetranor-PGE2-carboxamide (CP-34089/ZK-57671, sulprostone).

  DOI：

  10.1021/jm00143a018

文献信息

• Synthesis of Prostaglandins III:¹Efficient and Practical Synthesis of Antisecretory Prostaglandin Enprostil
  作者：Yong Sup Lee、Kee Hong Nam、Sun Ho Jung、Hokoon Park

  DOI：10.1055/s-1994-25576

  日期：——

  An efficient and practical 8-step synthesis of enprostil (1) starting from the lactone 2 has been developed. The propargylic acetate 5 was prepared from the lactol 3 by the reaction with ethynylmagnesium bromide followed by acetylation. Propargylic acetate 5 was converted into enprostil (1) via the introduction of an allene moity by reaction with a Grignard reagent in the presence of a CuI · P(OEt)3 complex.

  从内酯 2 开始，我们开发出了一种高效实用的 8 步合成法来合成恩诺地尔（1）。内酯 3 与乙炔溴化镁反应后进行乙酰化，制备出丙炔基乙酸酯 5。在 CuI - P(OEt)3 复合物存在的情况下，通过与格氏试剂反应引入烯烃，丙炔基乙酸酯 5 被转化为烯丙司地尔 (1)。
• Synthesis of the four stereoisomers of enprostil
  作者：Gary F. Cooper、Douglas L. Wren、David Y. Jackson、Colin C. Beard、Edvige Galeazzi、Albert R. Van Horn、Tsung T. Li

  DOI：10.1021/jo00068a023

  日期：1993.7

  The four stereoisomeric components of enprostil (1a-d) were prepared using an orthoester Claisen rearrangement of individual propargylic alcohol intermediates 8 to generate the required allene upper chain stereochemistry, followed by one-carbon homologation. All four of the key propargylic alcohols 8 were prepared by addition of ethynyl Grignard reagent to aldehyde 7 (and to its enantiomer) and chromatographic separation of the diastereomers. Isomer 8a was also prepared by asymmetric reduction of propargylic ketone 10, which was in turn efficiently prepared by the opening of lactone 3 with dichlorocerium acetylide followed by silylation. Propargylic alcohol 8a was stereospecifically converted to enprostil isomer 1a via reaction of the inverted propargylic bromide 21 with the three-carbon functionalized organocuprate 22, easily prepared from methyl 3-bromopropionate.
• US4894391A
  申请人：——

  公开号：US4894391A

  公开（公告）日：1990-01-16
• N-(Methanesulfonyl)-16-phenoxyprostaglandin carboxamides: tissue-selective, uterine stimulants
  作者：Thomas K. Schaaf、Jasjit S. Bindra、James F. Eggler、Jacob J. Plattner、A. James Nelson、M. Ross Johnson、Jay W. Constantine、Hans-Juergen Hess、Walter Elger

  DOI：10.1021/jm00143a018

  日期：1981.11

  In an effort to develop tissue-selective prostaglandin analogues resistant to the metabolic inactivating pathways of the natural materials, hybrid compounds modified both at C-1 with a sulfonimide moiety and in the n-amylcarbinol side chain with substituted phenoxy groups were synthesized and evaluated in a variety of in vitro models. Several of these analogues exhibited potent, tissue-selective, uterine stimulant activity, a finding subsequently confirmed in clinical studies with one member of this series, N-(methanesulfonyl)-16-phenoxy-omega-tetranor-PGE2-carboxamide (CP-34089/ZK-57671, sulprostone).