2-trimethylsilylethyl (2S,3S,5R,6R,8S)-6,8-dimethyl-2-[(2S,4R)-4-methyl-6-trimethylstannyl-3,4-dihydro-2H-pyran-2-yl]-3-triethylsilyloxy-1-oxa-10-azaspiro[4.5]decane-10-carboxylate | 615284-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 2-trimethylsilylethyl (2S,3S,5R,6R,8S)-6,8-dimethyl-2-[(2S,4R)-4-methyl-6-trimethylstannyl-3,4-dihydro-2H-pyran-2-yl]-3-triethylsilyloxy-1-oxa-10-azaspiro[4.5]decane-10-carboxylate
• CAS: 615284-68-9
• 化学式: C₃₁H₆₁NO₅Si₂Sn
• 分子量: 702.71
• InChiKey: WLVMNRKHFJEHCB-OIUCREJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  、 2-trimethylsilylethyl (2S,3S,5R,6R,8S)-6,8-dimethyl-2-[(2S,4R)-4-methyl-6-trimethylstannyl-3,4-dihydro-2H-pyran-2-yl]-3-triethylsilyloxy-1-oxa-10-azaspiro[4.5]decane-10-carboxylate 在 tris-(dibenzylideneacetone)dipalladium(0) 三苯胂 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 4.0h， 以63%的产率得到
  参考文献：
  名称：

  Total Synthesis and Structural Elucidation of Azaspiracid-1. Synthesis-Based Analysis of Originally Proposed Structures and Indication of Their Non-Identity to the Natural Product

  摘要：

  The key building blocks (6, 7, and 8) for the intended construction of the originally proposed structures of azaspiracid-1, a potent marine-derived neurotoxin, were coupled and the products elaborated to the targeted compounds (1a,b) and their C-20 epimers (2 and 3). The assembly of the three intermediates was accomplished by a dithiane-based coupling reaction that united the C-1 - C-20 (7) and C-21 - C-27 (8) fragments, followed by a Stille-type coupling which allowed the incorporation of the C-28 - C-40 fragment (6) into the growing substrate. Neither of the final products (1a,b) matched the natural substance by TLC or H-1 NMR spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this notorious biotoxin.

  DOI：

  10.1021/ja054748z
• 作为产物：
  描述：

  六甲基二锡 、 (2S,3S,5R,8S,10R)-8,10-Dimethyl-2-((2S,4R)-4-methyl-6-trifluoromethanesulfonyloxy-3,4-dihydro-2H-pyran-2-yl)-3-triethylsilanyloxy-1-oxa-6-aza-spiro[4.5]decane-6-carboxylic acid 2-trimethylsilanyl-ethyl ester 在 三(2-呋喃基)膦 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 以98%的产率得到2-trimethylsilylethyl (2S,3S,5R,6R,8S)-6,8-dimethyl-2-[(2S,4R)-4-methyl-6-trimethylstannyl-3,4-dihydro-2H-pyran-2-yl]-3-triethylsilyloxy-1-oxa-10-azaspiro[4.5]decane-10-carboxylate
  参考文献：
  名称：

  Azaspiracid-1 的全合成和结构解析。为原提议的结构建造关键积木

  摘要：

  描述了对所提出的 azaspiracid-1 (1a) 结构进行全合成所需的三个关键构件（65、98 和 100）的合成。关键步骤包括 TMSOTf 诱导的闭环级联以形成四环 65 的 ABC 环、用于构建中间体 98 的钕催化的内部氨基形成以及用于组装所需片段碳链的 Nozaki-Hiyama-Kishi 偶联100. 以两种对映体形式立体选择性地获得的合成片段有望构建所有四种立体异构体，作为 azaspiracid-1 (1a-d) 的可能结构，从而可以确定相对和绝对立体化学的天然产物。

  DOI：

  10.1021/ja0547477

文献信息

• Total Synthesis and Structural Elucidation of Azaspiracid-1. Final Assignment and Total Synthesis of the Correct Structure of Azaspiracid-1
  作者：K. C. Nicolaou、Theocharis V. Koftis、Stepan Vyskocil、Goran Petrovic、Wenjun Tang、Michael O. Frederick、David Y.-K. Chen、Yiwei Li、Taotao Ling、Yoichi M. A. Yamada

  DOI：10.1021/ja054750q

  日期：2006.3.1

  strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C(21)-C(27) fragment) reacting with a pentafluorophenol ester (C(1)-C(20) fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C(1)-C(27) fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1

  azaspiracid-1 是一种从贻贝中分离出的神经毒素，其分子结构已通过全合成阐明，这也丰富了其供应。这种海洋生物毒素的降解衍生片段化合物 5 (EFGHI)、6 (FGHI) 和 40 (ABCD) 与合成材料相匹配，从而证实了它们的结构特性。在此基础上，通过全合成提出并构建了azaspiracid-1(即1)的新结构。azaspiracid-1 全合成的最终策略是二噻烷阴离子（C(21)-C(27) 片段）与五氟苯酚酯（C(1)-C(20) 片段）反应，然后是 Stille 型高级烯丙基乙酸酯底物（C（1）-C（27）片段）与乙烯基锡烷的结合作为主要的偶联过程，以组装分子的碳骨架。
• Structural Revision and Total Synthesis of Azaspiracid-1, Part 1: Intelligence Gathering and Tentative Proposal
  作者：K. C. Nicolaou、Stepan Vyskocil、Theocharis V. Koftis、Yoichi M. A. Yamada、Taotao Ling、David Y.-K. Chen、Wenjun Tang、Goran Petrovic、Michael O. Frederick、Yiwei Li、Masayuki Satake

  DOI：10.1002/anie.200460695

  日期：2004.8.20
• Total Synthesis of the Proposed Azaspiracid-1 Structure, Part 2: Coupling of the C1–C20, C21–C27, and C28–C40 Fragments and Completion of the Synthesis
  作者：K. C. Nicolaou、David Y.-K. Chen、Yiwei Li、Wenyuan Qian、Taotao Ling、Stepan Vyskocil、Theocharis V. Koftis、Mugesh Govindasamy、Noriaki Uesaka

  DOI：10.1002/anie.200351826

  日期：2003.8.11
• Total Synthesis and Structural Elucidation of Azaspiracid-1. Synthesis-Based Analysis of Originally Proposed Structures and Indication of Their Non-Identity to the Natural Product
  作者：K. C. Nicolaou、David Y.-K. Chen、Yiwei Li、Noriaki Uesaka、Goran Petrovic、Theocharis V. Koftis、Federico Bernal、Michael O. Frederick、Mugesh Govindasamy、Taotao Ling、Petri M. Pihko、Wenjun Tang、Stepan Vyskocil

  DOI：10.1021/ja054748z

  日期：2006.2.1

  The key building blocks (6, 7, and 8) for the intended construction of the originally proposed structures of azaspiracid-1, a potent marine-derived neurotoxin, were coupled and the products elaborated to the targeted compounds (1a,b) and their C-20 epimers (2 and 3). The assembly of the three intermediates was accomplished by a dithiane-based coupling reaction that united the C-1 - C-20 (7) and C-21 - C-27 (8) fragments, followed by a Stille-type coupling which allowed the incorporation of the C-28 - C-40 fragment (6) into the growing substrate. Neither of the final products (1a,b) matched the natural substance by TLC or H-1 NMR spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this notorious biotoxin.
• Total Synthesis and Structural Elucidation of Azaspiracid-1. Construction of Key Building Blocks for Originally Proposed Structure
  作者：K. C. Nicolaou、Petri M. Pihko、Federico Bernal、Michael O. Frederick、Wenyuan Qian、Noriaki Uesaka、Nicole Diedrichs、Jürgen Hinrichs、Theocharis V. Koftis、Eriketi Loizidou、Goran Petrovic、Manuela Rodriquez、David Sarlah、Ning Zou

  DOI：10.1021/ja0547477

  日期：2006.2.1

  required for the total synthesis of the proposed structure of azaspiracid-1 (1a) are described. Key steps include a TMSOTf-induced ring-closing cascade to form the ABC rings of tetracycle 65, a neodymium-catalyzed internal aminal formation for the construction of intermediate 98, and a Nozaki-Hiyama-Kishi coupling to assemble the required carbon chain of fragment 100. The synthesized fragments, obtained stereoselectively

  描述了对所提出的 azaspiracid-1 (1a) 结构进行全合成所需的三个关键构件（65、98 和 100）的合成。关键步骤包括 TMSOTf 诱导的闭环级联以形成四环 65 的 ABC 环、用于构建中间体 98 的钕催化的内部氨基形成以及用于组装所需片段碳链的 Nozaki-Hiyama-Kishi 偶联100. 以两种对映体形式立体选择性地获得的合成片段有望构建所有四种立体异构体，作为 azaspiracid-1 (1a-d) 的可能结构，从而可以确定相对和绝对立体化学的天然产物。