9,9-dimethyl-1,4-dioxaspiro[4.5]dec-6-en-8-one | 851857-00-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 9,9-dimethyl-1,4-dioxaspiro[4.5]dec-6-en-8-one
• CAS: 851857-00-6
• 化学式: C₁₀H₁₄O₃
• 分子量: 182.219
• InChiKey: SZJYBXRQNUBDKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9,9-dimethyl-1,4-dioxaspiro[4.5]dec-6-en-8-one 在 2,6-二甲基吡啶 、 dimethyl sulfide borane 、 Pt[P(OH)(CH₃)2]3H 、 (S)-1-Me-3,3-Ph₂-hexahydropyrrolo[1,2-c][1,3,2]oxaborole 、 硫酸 、 水 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 丙酮 、 甲苯 为溶剂， 反应 174.25h， 生成 tert-butyl (2R)-2-[[(1R,5R)-5-[tert-butyl(diphenyl)silyl]oxy-6,6-dimethyl-2-oxocyclohex-3-en-1-yl]methyl]-2-carbamoylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Stephacidin B的对映选择性合成

  摘要：

  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

  DOI：

  10.1021/ja0510616
• 作为产物：
  描述：

  7,7-dimethyl-1,4-dioxaspiro[4.5]decan-8-one 在 正丁基锂 、 六甲基二硅氮烷 、 三甲基氯硅烷 、 palladium diacetate 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 49.25h， 以98%的产率得到9,9-dimethyl-1,4-dioxaspiro[4.5]dec-6-en-8-one
  参考文献：
  名称：

  Stephacidin B的对映选择性合成

  摘要：

  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

  DOI：

  10.1021/ja0510616

文献信息

• 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：——
• The selectivity of 6-nor-ABA and 7′-nor-ABA for abscisic acid receptor subtypes
  作者：Jun Takeuchi、Toshiyuki Ohnishi、Masanori Okamoto、Yasushi Todoroki

  DOI：10.1016/j.bmcl.2015.06.088

  日期：2015.9

  Abscisic acid (ABA), a plant hormone, is involved in many plant development processes and environmental stress responses that are regulated by a Pyrabactin Resistant 1 (PYR)/Pyrabactin Resistant-Like (PYL)/Regulatory Component of ABA Receptor (RCAR) receptor protein-mediated signal transduction pathway. In Arabidopsis thaliana, PYL proteins constitute a 14-member family comprising two distinct subclasses: dimeric receptors (PYR1 and PYL1-PYL3) and monomeric receptors (PYL4-PYL13). The individual contributions of PYL subclasses/subtypes with specific physiological actions are still poorly understood; consequently, the development of PYL subclass/subtype-selective agonists should be useful to reveal the different functions of these receptors. In this study, we focused on the ABA analogs 6-norABA and 70-nor-ABA, which were expected to function as monomeric receptor-selective agonists on the basis of crystal structures of PYL-ABA complexes and sequence alignments of PYL subtypes. In a protein phosphatase 2C (PP2C) assay, the agonist activities of both analogs were lower than those of ABA toward all tested PYL proteins, regardless of subclass/subtype. Nevertheless, we found that 6-nor-ABA acts as a selective agonist at the physiological level: it induced stomatal closure but did not inhibit seed germination and root growth. On the basis of observed inhibitory activity against PP2C among different PYL subtypes, this biological effect of 6-nor-ABA may be attributed to the activity of that agonist on PYL5 and/or PYL6. (C) 2015 Elsevier Ltd. All rights reserved.
• US7902196B2
  申请人：——

  公开号：US7902196B2

  公开（公告）日：2011-03-08