methyl [2R-(2α,5β,6α)]-6-acetyl-5-methyltetrahydro-2H-pyran-2-acetate | 176302-23-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: methyl [2R-(2α,5β,6α)]-6-acetyl-5-methyltetrahydro-2H-pyran-2-acetate
• 英文别名: methyl 2-((2R,5S,6S)-6-acetyl-5-methyltetrahydro-2H-pyran-2-yl)acetate；methyl 2-[(2R,5S,6S)-6-acetyl-5-methyloxan-2-yl]acetate
• CAS: 176302-23-1
• 化学式: C₁₁H₁₈O₄
• 分子量: 214.262
• InChiKey: DDWGLPFPHKVLKW-NMLBEHRDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl [2R-(2α,5β,6α)]-6-acetyl-5-methyltetrahydro-2H-pyran-2-acetate 在 chromium dichloride 、 盐酸 、 叔丁基过氧化氢 、 四(三苯基膦)钯 、 bis(acetylacetonate)oxovanadium 、 caesium carbonate 、 三甲基氢氧化锡 作用下， 以 四氢呋喃 、 甲醇 、 1,1-二氯乙烷 、 苯 为溶剂， 反应 8.5h， 生成 3-{[(6,7-二乙氧基-1,2,3,4-四氢萘-2-基)氨基]甲基}-6-(乙烯氧基)环己-2,4-二烯-1-酮盐酸
  参考文献：
  名称：

  A Stereoselective Synthesis of (+)-Herboxidiene/GEX1A

  摘要：

  A stereoselective synthesis of (+)-herboxidiene is described. The convergent synthesis utilized a Suzuki cross-coupling reaction to assemble the key segments. The synthesis of the functionalized tetrahydropyran ring utilized an Achmatowicz reaction as the key step. The synthesis of the C10-C19 segment was accomplished using Brown's crotylboration, asymmetric alkylation, and a stereoselective allylic chlorination reactions.

  DOI：

  10.1021/ol102549a
• 作为产物：
  描述：

  3-{[(6,7-二乙氧基-1,2,3,4-四氢萘-2-基)氨基]甲基}-6-(乙烯氧基)环己-2,4-二烯-1-酮盐酸 在 盐酸 、 二甲基硫 、 臭氧 作用下， 反应 4.0h， 生成 methyl [2R-(2α,5β,6α)]-6-acetyl-5-methyltetrahydro-2H-pyran-2-acetate
  参考文献：
  名称：

  草oxid烯：通过降解和合成研究确定绝对构型

  摘要：

  新的聚酮化合物除草剂除草二烯的降解导致有用的片段用于进一步的类似物合成，并且还能够通过各个片段的不对称合成来确定天然产物的绝对构型。

  DOI：

  10.1016/s0040-4020(97)00021-5

文献信息

• Design and synthesis of herboxidiene derivatives that potently inhibit <i>in vitro</i> splicing
  作者：Arun K. Ghosh、Srinivasa Rao Allu、Guddeti Chandrashekar Reddy、Adriana Gamboa Lopez、Patricia Mendez、Melissa S. Jurica

  DOI：10.1039/d0ob02532a

  日期：——

  potent less complex structures would be of interest as a drug lead as well as a tool for studying SF3B1 function in splicing. We investigated a number of C-6 modified herboxidiene derivatives in an effort to eliminate this stereocenter and, also to understand the importance of this functionality. The syntheses of structural variants involved a Suzuki–Miyaura cross-coupling reaction as the key step. The

  Herboxidiene 是一种有效的抗肿瘤剂，靶向剪接体的 SF3B 亚基。Herboxidiene 具有具有九个立体中心的复杂结构结构，并且有效的不太复杂结构的设计作为药物先导以及研究剪接中 SF3B1 功能的工具将是令人感兴趣的。我们研究了许多 C-6 修饰的 Herboxidiene 衍生物，以努力消除这种立体中心，并了解这种功能的重要性。结构变体的合成涉及铃木-宫浦交叉偶联反应作为关键步骤。功能化的四氢呋喃核心由市售的光学活性三-O-乙酰-D-葡聚糖。我们研究了这些衍生物对剪接化学的影响。C-6 烯烃衍生物显示出非常有效的剪接抑制活性，类似于herboxidiene。此外，C-6偕二甲基衍生物还表现出非常有效的体外剪接抑制活性，可与herboxidiene 相媲美。
• Improved synthetic route to enantiomerically pure samples of the tetrahydropyran-2-ylacetic acid core associated with the phytotoxic polyketide herboxidiene
  作者：Martin G. Banwell、Malcolm D. McLeod、Rajaratnam Premraj、Gregory W. Simpson

  DOI：10.1071/ch00083

  日期：——

  The phosphine oxide (2), which embodies the tetrahydropyran-2-ylacetic acid core associated with the phytotoxic polyketide herboxidiene (1) and which is a key intermediate in a projected synthesis of this natural product, has been prepared in a highly enantio- and diastereo-selective manner. The pivotal steps in this new and improved synthesis of compound (2) involve Katsuki–Sharpless asymmetric epoxidation of the allylic alcohol (4) to give epoxide (7) and subsequent ring-cleavage of the latter compound with trimethylaluminium to give diol (9). The derived acetate (10) is then readily ozonolysed to give the previously reported aldehyde (11), although now in high enantiomeric excess. Compound (11) can be elaborated, by established chemistry, to the target oxide (2).

  氧化膦（2）含有与植物毒性多酮雌脒烯（1）相关的四氢吡喃-2-基乙酸核心，是一种具有植物毒性的多酮雌脒烯（1）。 氧化膦（2）含有与植物毒性多酮herboxidiene（1）相关的四氢吡喃-2-基乙酸核心，是预计合成这种天然产物的关键中间体。 的关键中间体。 以高度对映和非对映选择性的方式制备出来。这种 的关键步骤包括 烯丙基醇 (4) 的 Katsuki-Sharpless 不对称环氧化反应，得到环氧化物 (7)。 得到环氧化物 (7)，随后用三甲基铝对后者进行环裂解，得到二元醇。 三甲基铝进行裂环，得到二元醇 (9)。得到的乙酸酯（10）很容易被 臭氧分解，得到之前报告过的醛 (11)，不过现在对映体过量。 对映体过量。化合物 (11) 可以通过成熟的 化学反应，得到目标氧化物 (2)。
• A Total Synthesis of Herboxidiene Methyl Ester
  作者：Martin G. Banwell、Rajaratnam Premraj、Malcolm D. McLeod、Gregory W. Simpson

  DOI：10.3987/com-12-12597

  日期：——

  The total synthesis of the methyl ester, 35, of herboxidiene (1, a.k.a. GEX1A and TAN-1609), a polyketide displaying both herbicidal and anti-tumor activity, is described. The convergent reaction sequence involves, in its closing stages, the union of the phosphine oxide 3 with the aldehyde 21 to deliver, via a Horner-Wittig reaction with accompanying epimerization at C12, compound 33 that after deprotection affords an alcohol, 34, capable of participating in a regio- and diastereo-selective epoxidation reaction to give target 35. Phosphine oxide 3 was prepared via the intramolecular hetero-Michael addition of a secondary alcohol to a tethered and Z-configured acrylate while aldehyde 21 was generated, in the crucial step of the relevant reaction sequence, via an Ireland-Claisen rearrangement reaction.
• Pre-mRNA Splicing-Modulatory Pharmacophores: The Total Synthesis of Herboxidiene, a Pladienolide–Herboxidiene Hybrid Analog and Related Derivatives
  作者：Chandraiah Lagisetti、Maria V. Yermolina、Lalit Kumar Sharma、Gustavo Palacios、Brett J. Prigaro、Thomas R. Webb

  DOI：10.1021/cb400695j

  日期：2014.3.21

  Herboxidiene is a natural product that has previously been shown to exhibit antitumor activity by targeting the spliceosome. This activity makes herboxidiene a valuable starting point for the development of anticancer drugs. Here, we report an improved enantioselective synthesis of herboxidiene and the first report of its biologically active totally synthetic analog: 6-norherboxidiene. The synthesis of the tetrahydropyran moiety utilizes the novel application of inverse electron-demand Diels-Alder chemistry and the Ferrier-type rearrangement as key steps. We report, for the first time, cytotoxicity IC(50)s for synthetic herboxidiene and analogs in human tumor cell lines. We have also demonstrated that synthetic herboxidiene and its analogs can potently modulate the alternate splicing of MDM-2 pre-mRNA.
• Banwell, Martin G.; Bui, Chinh T.; Simpson, Gregory W., Journal of the Chemical Society. Perkin transactions I, 1998, # 4, p. 791 - 799
  作者：Banwell, Martin G.、Bui, Chinh T.、Simpson, Gregory W.

  DOI：——

  日期：——