2,2-dimethyl-6-iodo-5-nitro-2H-1-benzopyran | 200814-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2,2-dimethyl-6-iodo-5-nitro-2H-1-benzopyran
• 英文别名: 2H-1-Benzopyran, 6-iodo-2,2-dimethyl-5-nitro-；6-iodo-2,2-dimethyl-5-nitrochromene
• CAS: 200814-22-8
• 化学式: C₁₁H₁₀INO₃
• 分子量: 331.11
• InChiKey: BUIMTKJLGZOIJB-UHFFFAOYSA-N

物化性质

• 沸点：
  371.7±42.0 °C(Predicted)
• 密度：
  1.716±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-6-iodo-5-nitro-2H-1-benzopyran 在 盐酸 、 palladium diacetate 、 potassium carbonate 、 三苯基膦 、 tin(ll) chloride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 21.5h， 生成 1,8-二氢-8,8-二甲基吡喃并[2,3]喹啉-2-酮
  参考文献：
  名称：

  The First Regiospecific Synthesis of 8,8-Dimethyl-2H,8H-pyrano[2,3-h]quinolin-2-one and Related Compounds

  摘要：

  标题化合物经过八步合成，起始于6-乙酰氨基-2,3-二甲基-2H-1-苯并吡喃-4-酮（6）。关键步骤包括6的区域选择性硝化反应以及在水相介质中钯(0)催化的丙烯酸酰氨基化反应。

  DOI：

  10.1055/s-1997-1350
• 作为产物：
  描述：

  6-acetamido-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-one 在 盐酸 、 sodium tetrahydroborate 、 硝酸 、 对甲苯磺酸 、 potassium iodide 、 sodium nitrite 作用下， 以 甲醇 、 乙醇 、 溶剂黄146 、 甲苯 为溶剂， 反应 41.75h， 生成 2,2-dimethyl-6-iodo-5-nitro-2H-1-benzopyran
  参考文献：
  名称：

  The First Regiospecific Synthesis of 8,8-Dimethyl-2H,8H-pyrano[2,3-h]quinolin-2-one and Related Compounds

  摘要：

  标题化合物经过八步合成，起始于6-乙酰氨基-2,3-二甲基-2H-1-苯并吡喃-4-酮（6）。关键步骤包括6的区域选择性硝化反应以及在水相介质中钯(0)催化的丙烯酸酰氨基化反应。

  DOI：

  10.1055/s-1997-1350

文献信息

• Enantioselective Synthesis of Stephacidin B
  作者：Seth B. Herzon、Andrew G. Myers

  DOI：10.1021/ja0510616

  日期：2005.4.1

  yloxymethyl)-2,3-dihydropyrrole in a stereoselective enolate alkylation, a diastereoselective Strecker-type addition of hydrogen cyanide to an N-Boc enamine substrate in the solvent hexafluoroisopropanol, platinum-catalyzed nitrile hydrolysis under neutral conditions, cyclization of an acylamino radical intermediate to form the diketopiperazine core of stephacidin B, and implementation of a convergent

  我们描述了一种对映选择性合成抗增殖生物碱 stepphacidin B (1) 的路线，该路线分 18 个步骤进行，从 4,4-(亚乙基二氧基)-2,2-二甲基环己酮 (3) 的产率为 4.0%。合成序列的关键特征包括使用 Corey-Bakshi-Shibata (CBS) 还原在合成路线的早期引入不对称性，使用新型亲电子试剂 N-(叔丁氧基羰基)-5-(异丙基磺酰氧基甲基)-2， 3-二氢吡咯在立体选择性烯醇化物烷基化中，氰化氢与 N-Boc 烯胺底物在六氟异丙醇溶剂中的非对映选择性 Strecker 型加成，铂催化的腈在中性条件下水解，酰氨基中间体环化形成二酮哌嗪核百日咳菌素 B，并实施收敛程序以在路线的最后阶段引入关键的 3-亚烷基-3H-吲哚 1-氧化物官能团以制备结构 2，先前提出为真菌代谢物 avrainvillamide（17 个步骤，4.2%屈服）。我们观察到合成的 (-)-2
• SYNTHESIS OF AVRAINVILLAMIDE, STEPHACIDIN B, AND ANALOGUES THEREOF
  申请人：Myers Andrew G.

  公开号：US20110166170A1

  公开（公告）日：2011-07-07

  The syntheses of the natural products, avrainvillamide and stephacidin B, are provided. The α,β-unsaturated nitrone functionality of avrainvillamide and its 3-alkylidene-3H-indole 1-oxide core is shown to covalently and reversibly bond to heteroatom-based nucleophiles. This capability may allow these molecules to bind active site nucleophiles and may provide the basis for designing potent and selective enzyme inhibitors. Both avrainvillamide and its dimer stephacidin B have been reported to exhibit antiproliferative activity, and avrainvillamide has been reported to exhibit antimicrobial activity against multi-drug resistant bacteria. Avrainvillamide has been found to target cytoskeleton-linking membrane protein (CLIMP-63) thereby preventing cells from undergoing mitosis. The invention provides syntheses of these natural products as well as analogs of these natural products and their functional cores. The compounds of the invention may be used in the treatment of diseases such as cancer, autoimmune diseases, and bacterial infection.

  本文介绍了自然产物avrainvillamide和stephacidin B的合成方法。其中，avrainvillamide的α,β-不饱和亚硝基功能团和其3-烷基亚甲基-3H-吲哚1-氧化物核心被证明能够与杂原子型亲核试剂共价、可逆结合。这种能力可能使这些分子能够结合活性位点的亲核试剂，并为设计有效且选择性的酶抑制剂提供基础。avrainvillamide和其二聚体stephacidin B均已被报道具有抗增殖活性，而avrainvillamide还被报道对多重耐药菌具有抗菌活性。研究发现，avrainvillamide能够靶向细胞骨架连接膜蛋白（CLIMP-63），从而防止细胞进行有丝分裂。本发明提供了这些天然产物以及它们的类似物和功能核心的合成方法。这些化合物可以用于治疗癌症、自身免疫性疾病和细菌感染等疾病。
• SYNTHESIS OF AVRAINVILLAMIDE, STREPHACIDIN B, AND ANALOGUES THEREOF
  申请人：Myers Andrew G.

  公开号：US20090143581A1

  公开（公告）日：2009-06-04

  The syntheses of the natural products, avrainvillamide and stephacidin B, are provided. The α,β-unsaturated nitrone functionality of avrainvillamide and its 3-alkylidene-3H-indole 1-oxide core is shown to covalently and reversibly bond to heteroatom-based nucleophiles. This capability may allow these molecules to bind active site nucleophiles and may provide the basis for designing potent and selective enzyme inhibitors. Both avrainvillamide and its dimer stephacidin B have been reported to exhibit antiproliferative activity, and avrainvillamide has been reported to exhibit antimicrobial activity against multi-drug resistant bacteria. Avrainvillamide has been found to target cytoskeleton-linking membrane protein (CLIMP-63) thereby preventing cells from undergoing mitosis. The invention provides syntheses of these natural products as well as analogs of these natural products and their functional cores. The compounds of the invention may be used in the treatment of diseases such as cancer, autoimmune diseases, and bacterial infection.

  本文提供了天然产物avrinvillamide和stephacidin B的合成方法。avrinvillamide的α，β-不饱和亚硝基功能和其3-烷基亚甲基-3H-吲哚1-氧化物核心被证明可以共价可逆地结合到基于杂原子的亲核试剂上。这种能力可能使这些分子能够结合到活性位点的亲核试剂，并为设计有效和选择性的酶抑制剂提供基础。avrinvillamide和其二聚体stephacidin B均已报道具有抗增殖活性，avrinvillamide也已报道具有对多药耐药细菌的抗菌活性。发现avrinvillamide的靶点是细胞骨架连接膜蛋白(CLIMP-63)，从而防止细胞进行有丝分裂。本发明提供了这些天然产物以及它们的类似物和功能核心的合成方法。本发明的化合物可以用于治疗癌症、自身免疫性疾病和细菌感染等疾病。
• WO2006/102097
  申请人：——

  公开号：——

  公开（公告）日：——
• Evidence for the Rapid Conversion of Stephacidin B into the Electrophilic Monomer Avrainvillamide in Cell Culture
  作者：Jeremy E. Wulff、Seth B. Herzon、Romain Siegrist、Andrew G. Myers

  DOI：10.1021/ja0690971

  日期：2007.4.1

  We report that the dimeric alkaloid stephacidin B (1) and the monomeric alkaloid avrainvillamide (2) function equivalently within experimental error to inhibit the growth of four different cultured human cancer cell lines. We also show that the proportion of the monomer greatly outweighs that of the dimer in the medium of incubation, and that the half-life for the transformation of 1 to 2 is short relative to the half-life of cell division. Finally, using a monomer-based affinity reagent, we provide evidence that the monomer (2) interacts with intracellular thiol-containing proteins, likely by covalent modification.