(1'R,6'S)-4'-bromospiro[1,3-dioxane-2,5'-7-oxabicyclo[4.1.0]hept-3-ene]-2'-one | 620949-67-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1'R,6'S)-4'-bromospiro[1,3-dioxane-2,5'-7-oxabicyclo[4.1.0]hept-3-ene]-2'-one
• CAS: 620949-67-9
• 化学式: C₉H₉BrO₄
• 分子量: 261.072
• InChiKey: SGQXSKLCBMGXCI-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  48.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1'R,6'S)-4'-bromospiro[1,3-dioxane-2,5'-7-oxabicyclo[4.1.0]hept-3-ene]-2'-one 在 zirconium(IV) tert-butoxide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  螺异恶唑啉天然产物（+）-卡拉芬宁的全合成和立体化学分配。

  摘要：

  已报道使用不对称亲核环氧化和一氧化氮环加成作为关键步骤合成螺异异唑啉天然产物（+）-卡拉夫宁。所有卡拉芬宁立体异构体的合成和光谱分析导致相对和绝对立体化学的明确分配。

  DOI：

  10.1021/ol053115m
• 作为产物：
  描述：

  11-Bromo-1,5-dioxaspiro[5.5]undeca-7,10-dien-9-one 在 L-(+)-酒石酸二异丙酯 、 sodium hexamethyldisilazane 作用下， 以 甲苯 为溶剂， 反应 15.0h， 生成 (1'R,6'S)-4'-bromospiro[1,3-dioxane-2,5'-7-oxabicyclo[4.1.0]hept-3-ene]-2'-one
  参考文献：
  名称：

  Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines

  摘要：

  转录因子NF-κB活性增加与许多B细胞淋巴瘤相关。我们研究了合成化合物calafianin单体（CM101）对NF-κB的生化和生物学特性的影响。在人类293细胞中，CM101选择性抑制了过表达的NF-κB亚单位REL（人类c-Rel）和p65的DNA结合，而NF-κB p50的DNA结合未受到影响。CM101对REL和p65 DNA结合的抑制需要一个保守的半胱氨酸残基。CM101还在几种人类B淋巴瘤细胞系中抑制了REL的DNA结合，且几种B淋巴瘤细胞系对CM101诱导的增殖停滞和细胞凋亡的敏感性与细胞和核内REL的水平相关。CM101处理引起了敏感B淋巴瘤细胞系中抗凋亡蛋白Bcl-XL的磷酸化和表达降低，Bcl-XL是REL的靶基因产物。异位表达Bcl-XL保护了SUDHL-2 B淋巴瘤细胞免受CM101诱导的凋亡，而REL的转化突变体的过表达降低了BJAB B淋巴瘤细胞对CM101诱导凋亡的敏感性。脂多糖诱导的NF-κB信号上游组分在CM101浓度下被激活，而该浓度能够阻止NF-κB DNA结合。直接抑制REL的化合物可能对那些REL活跃的B细胞淋巴瘤的治疗有用，并可能在不影响正常细胞某些免疫相关反应的剂量下抑制B淋巴瘤细胞生长。

  DOI：

  10.3390/molecules20057474

文献信息

• Toward the Total Synthesis of Scabrosins: Synthesis of a Desulfur-scabrosin Skeleton and Its Stereoisomers
  作者：Yuyin Liu、Zhi-Peng Wang、Sreenivas Banne、Jian Guo、Yun He

  DOI：10.1021/acs.joc.9b00015

  日期：2019.5.3

  The enantioselective synthesis of a desulfur-scabrosin skeleton was reported. The synthesis began from 3-(hydroxymethyl)phenol, and key steps include asymmetric nucleophilic epoxidation, a Mitsunobu reaction using a sulfonamide as the nucleophile, the construction of a pyrrolidine ring by intramolecular nucleophilic substitution, and inversion of configuration through base-induced keto–enol isomerization

  据报道，对映体选择性合成了脱硫核苷骨架。合成过程从3-（羟甲基）苯酚开始，关键步骤包括不对称亲核环氧化，使用磺酰胺作为亲核试剂的Mitsunobu反应，通过分子内亲核取代构建吡咯烷环，以及通过碱基诱导的酮基转化构型–烯醇异构化。另外，还通过另一种闭环策略获得了碳骨架的两个异构体。
• Stereocontrolled Synthesis of a Complex Library via Elaboration of Angular Epoxyquinol Scaffolds
  作者：Xiaoguang Lei、Nava Zaarur、Michael Y. Sherman、John A. Porco

  DOI：10.1021/jo050956y

  日期：2005.8.1

  We have accomplished the synthesis of a complex chemical library via elaboration of angular epoxyquinol scaffolds with distinct skeletal frameworks. The key strategy involves highly stereocontrolled [4 + 2] Diels-Alder cycloadditions of chiral, nonracemic epoxyquinol dienes to generate the scaffolds. Further scaffold diversification involves hydrogenation, epimerization, dehydration, and condensation of the carbonyl group with alkoxyamine and carbazate building blocks. Further elaboration of the scaffolds also provided new skeletal frameworks using hydroxyl-directed Diels-Alder cycloaddition and reductive N-N bond cleavage. The overall process afforded 244 highly complex and functionalized compounds. Preliminary biological screening of the library uncovered six compounds which showed significant inhibition of Hsp 72 induction.
• Total Synthesis of the Ubiquitin-Activating Enzyme Inhibitor (+)-Panepophenanthrin
  作者：Xiaoguang Lei、Richard P. Johnson、John A. Porco

  DOI：10.1002/anie.200351862

  日期：2003.8.25
• Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines
  作者：Alan Yeo、Spandan Chennamadhavuni、Adrian Whitty、John Porco、Thomas Gilmore

  DOI：10.3390/molecules20057474

  日期：——

  Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101) on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL (human c-Rel) and p65 as compared to NF-κB p50, and inhibition of REL and p65 DNA binding by CM101 required a conserved cysteine residue. CM101 also inhibited DNA binding by REL in human B-lymphoma cell lines, and the sensitivity of several B-lymphoma cell lines to CM101-induced proliferation arrest and apoptosis correlated with levels of cellular and nuclear REL. CM101 treatment induced both phosphorylation and decreased expression of anti-apoptotic protein Bcl-XL, a REL target gene product, in sensitive B-lymphoma cell lines. Ectopic expression of Bcl-XL protected SUDHL-2 B-lymphoma cells against CM101-induced apoptosis, and overexpression of a transforming mutant of REL decreased the sensitivity of BJAB B-lymphoma cells to CM101-induced apoptosis. Lipopolysaccharide-induced activation of NF-κB signaling upstream components occurred in RAW264.7 macrophages at CM101 concentrations that blocked NF-κB DNA binding. Direct inhibitors of REL may be useful for treating B-cell lymphomas in which REL is active, and may inhibit B-lymphoma cell growth at doses that do not affect some immune-related responses in normal cells.

  转录因子NF-κB活性增加与许多B细胞淋巴瘤相关。我们研究了合成化合物calafianin单体（CM101）对NF-κB的生化和生物学特性的影响。在人类293细胞中，CM101选择性抑制了过表达的NF-κB亚单位REL（人类c-Rel）和p65的DNA结合，而NF-κB p50的DNA结合未受到影响。CM101对REL和p65 DNA结合的抑制需要一个保守的半胱氨酸残基。CM101还在几种人类B淋巴瘤细胞系中抑制了REL的DNA结合，且几种B淋巴瘤细胞系对CM101诱导的增殖停滞和细胞凋亡的敏感性与细胞和核内REL的水平相关。CM101处理引起了敏感B淋巴瘤细胞系中抗凋亡蛋白Bcl-XL的磷酸化和表达降低，Bcl-XL是REL的靶基因产物。异位表达Bcl-XL保护了SUDHL-2 B淋巴瘤细胞免受CM101诱导的凋亡，而REL的转化突变体的过表达降低了BJAB B淋巴瘤细胞对CM101诱导凋亡的敏感性。脂多糖诱导的NF-κB信号上游组分在CM101浓度下被激活，而该浓度能够阻止NF-κB DNA结合。直接抑制REL的化合物可能对那些REL活跃的B细胞淋巴瘤的治疗有用，并可能在不影响正常细胞某些免疫相关反应的剂量下抑制B淋巴瘤细胞生长。
• Total Synthesis and Stereochemical Assignment of the Spiroisoxazoline Natural Product (+)-Calafianin¹
  作者：Sujata Bardhan、Daniel C. Schmitt、John A. Porco

  DOI：10.1021/ol053115m

  日期：2006.3.2

  Synthesis of the spiroisoxazoline natural product (+)-calafianin is reported using asymmetric nucleophilic epoxidation and nitrile oxide cycloaddition as key steps. Synthesis and spectral analysis of all calafianin stereoisomers led to unambiguous assignment of relative and absolute stereochemistry.

  已报道使用不对称亲核环氧化和一氧化氮环加成作为关键步骤合成螺异异唑啉天然产物（+）-卡拉夫宁。所有卡拉芬宁立体异构体的合成和光谱分析导致相对和绝对立体化学的明确分配。