1(β),2(β),6,7,7a(β),8,9,9a(α),9(β)-decahydro-2,9-epithio-7a-ethyl-1-phenyl-3H-cyclopentaquinolizin-3-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1(β),2(β),6,7,7a(β),8,9,9a(α),9(β)-decahydro-2,9-epithio-7a-ethyl-1-phenyl-3H-cyclopentaquinolizin-3-one
• 英文别名: (1S,2R,3R,6R,11S)-6-ethyl-2-phenyl-12-thia-10-azatetracyclo[8.2.1.03,11.06,11]tridecan-13-one
• 化学式: C₁₉H₂₃NOS
• 分子量: 313.464
• InChiKey: VVKPIPXPMKHJBC-DZBHQSCQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  哌啶酮 在 nickel boride 劳森试剂 、 copper(l) iodide 、 氢气 、 溴 、 双(三甲基硅烷基)氨基钾 、 三乙胺 、 三苯基膦 、 palladium dichloride 作用下， 反应 1.5h， 生成 1(β),2(β),6,7,7a(β),8,9,9a(α),9(β)-decahydro-2,9-epithio-7a-ethyl-1-phenyl-3H-cyclopentaquinolizin-3-one
  参考文献：
  名称：

  Cycloaddition Chemistry of Anhydro-4-hydroxy-1,3-thiazolium Hydroxides (Thioisomünchnones) for the Synthesis of Heterocycles

  摘要：

  一系列的α,α-二取代硫代异肟酮通过在三乙胺存在下，用溴乙酰氯处理非环状或环状硫代酰胺来制备。结果发现，这些介离子偶极体会发生双分子1,3-偶极环加成反应与多种不同的偶极体分子。当硫代酰胺的α-位上有氢原子时，最初形成的N-酰基亚胺离子会快速失去质子，产生S,N-酮烯醇缩醛，比形成硫代异肟酮的速度更快。还研究了几种带有附加烯烃的取代硫代异肟酮的环加成行为。内向环加成反应是邻近的π键跨过瞬态硫代异肟酮偶极子的结果，这是分子内反应的立体化学产物的成因。分子力学计算表明，内向非对映异构体的能量比相应的向外构体显著更低。尝试将硫代异肟酮偶极子环加成到附加的吲哚环上未能成功。相反，高产率地形成通过吲哚环以亲核方式环化到硫代N-酰基亚胺离子上的产物。

  DOI：

  10.1055/s-1994-25621

文献信息

• Application of Cross-Conjugated Heteroaromatic Betaines to the Synthesis of the Schizozygane Alkaloid (±)-Strempeliopine
  作者：Drew R. Bobeck、Hyoung Ik Lee、Andrew C. Flick、Albert Padwa

  DOI：10.1021/jo901336z

  日期：2009.10.2

  An efficient stereocontrolled route to the isoschizozygane alkaloid core has been developed utilizing an intramolecular 1,4-dipolar cycloaddition of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct undergoes loss of COS, and further reduction delivers a 5a-azaacenaphthylene intermediate that was transformed into the isoschizozygane skeleton upon treatment with acid. A variation

  利用交叉缀合的杂芳族甜菜碱的分子内1，4-偶极环加成，已经开发了一种有效的立体异构控制的途径，用于异麦芽糖胺生物碱核心。生成的环加合物经历了COS的损失，并且进一步的还原产生了5 a-氮杂ena庚烯中间体，其在用酸处理后被转化为异chi唑烷骨架。然后，采用这种策略的一种变体来合成zo唑烷生物碱（±）-倍他福洛平的六环骨架。合成的关键步骤对应于杂原子甜菜碱的分子内1,4-偶极环加成反应，该分子通过束缚的4-（（2-硝基苯基）丁-3-烯基）侧链。硝基的催化还原，然后与NBS反应导致形成目标生物碱所需的五环二氢吲哚骨架。使用氧化环化作用封闭了zo唑烷骨架的最后一个环。
• Cycloaddition Chemistry of Anhydro-4-hydroxy-1,3-thiazolium Hydroxides (Thioisomünchnones) for the Synthesis of Heterocycles
  作者：Albert Padwa、Scott R. Harring、Donald L. Hertzog、William R. Nadler

  DOI：10.1055/s-1994-25621

  日期：——

  A series of α,α-disubstituted thioisomünchnones were prepared by treating acyclic or cyclic thioamides with bromoacetyl chloride in the presence of triethylamine. The resulting mesoionic dipole was found to undergo bimolecular 1,3-dipolar cycloaddition with several different dipolarophiles. When a hydrogen atom is present in the α-position of the thioamide, the initially formed N-acyl iminium ion undergoes proton loss to produce a S,N-ketene acetal at a faster rate than thioisomünchnone formation. The cycloaddition behavior of several substituted thioisomünchnones which possess a tethered alkene were also examined. The stereochemical outcome of the intramolecular reaction is the consequence of an endo cycloaddition of the neighboring π-bond across the transient thioisomünchnone dipole. Molecular mechanics calculations reveal that the endo diastereomers are significantly lower in energy than the corresponding exo isomers. Attempts to cycloadd the thioisomünchnone dipole across a tethered indolyl ring were unsuccessful. Instead, products derived by nucleophilic cyclization of the indolyl ring onto the thio N-acyl iminium ion were formed in good yield.

  一系列的α,α-二取代硫代异肟酮通过在三乙胺存在下，用溴乙酰氯处理非环状或环状硫代酰胺来制备。结果发现，这些介离子偶极体会发生双分子1,3-偶极环加成反应与多种不同的偶极体分子。当硫代酰胺的α-位上有氢原子时，最初形成的N-酰基亚胺离子会快速失去质子，产生S,N-酮烯醇缩醛，比形成硫代异肟酮的速度更快。还研究了几种带有附加烯烃的取代硫代异肟酮的环加成行为。内向环加成反应是邻近的π键跨过瞬态硫代异肟酮偶极子的结果，这是分子内反应的立体化学产物的成因。分子力学计算表明，内向非对映异构体的能量比相应的向外构体显著更低。尝试将硫代异肟酮偶极子环加成到附加的吲哚环上未能成功。相反，高产率地形成通过吲哚环以亲核方式环化到硫代N-酰基亚胺离子上的产物。
• An Approach to the Isoschizozygane Alkaloid Core Using a 1,4-Dipolar Cycloaddition of a Cross-Conjugated Heteroaromatic Betaine
  作者：Albert Padwa、Andrew C. Flick、Hyoung Ik Lee

  DOI：10.1021/ol0508779

  日期：2005.7.1

  [reaction: see text] A new strategy for the synthesis of the isoschizozygane alkaloid core has been developed that is based on a 1,4-dipolar cycloaddition reaction of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct undergoes loss of COS, and further reduction delivers a 5a-aza-acenaphthylene intermediate that was transformed into the isoschizozygane skeleton upon treatment with

  [反应：见正文]基于交叉共轭杂芳族甜菜碱的1，4-偶极环加成反应，已开发出一种合成同工酶生物碱核心的新策略。所得的环加合物经历了COS的损失，并且进一步的还原产生了5a-氮杂-ph烯中间体，该中间体在用酸处理后被转化为异chi并zygane骨架。