Efficient Syntheses of Natural and Unnatural Benzotropolones and Pulvinones. Total Synthesis of the Fungal Dye Aurantricholone

天然和非天然苯并托酚酮和普维酮的高效合成。

• 批准号: 277682607
• 负责人: Professor Dr. Reinhard Brückner
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/277682607?language=en
• 关键词: Efficient; Syntheses; Natural; Unnatural; Benzotropolones

In 1945 a hydroxycycloheptatrienone was identified as the core of a fungal dye. This core was named tropolone. It represented the first charge-free isocyclic non-benzenoid aromatic compound. The annulation of benzene to tropolone defines the structures of 3,4- and 4,5-benzotropolone. The synthesis of 3,4-benzotropolones of diverse and arbitrarily variable substitution patterns is the main objective of our project. Synthetic 3,4-benzotropolone are preservatives and UV absorbers and act against microbes, retroviruses, and obesity. Synthetic 3,4-benzotropolone are also leads for the therapy of acne and sepsis. Theaflavin is another 3.4-benzotropolone, which is beneficial for health. It originates from the fermentation giving tea. 3,4-Benzotropolone natural products in the proper sense of the term exist in almost 40 variations. They comprise a fungal dye named aurantricholone. Achieving the first total synthesis of this compound is another goal of our project. Aurantricholone remained elusive when we tried to gain it by the oxidation of catechol/pyrogallol mixtures - i. e., in a single step and supposedly biomimetically. A likely reason for this failure could is that aurantricholone resembles a bis(pulvinone) because it contains two alpha-aryl-gamma-(arylmethylidene)tetronic acid moieties. The latter are prone to oxidations and even to autoxidation, particularly, when their aryl groups are polyphenols. This is well-known from the closely related pulvinic aicids. Hence, developing benzotropolone-tolerant pulvinone syntheses is another desideratum of this project.The foundations for three such pulvinone routes were established in our preparatory studies. Substituted 3,4-benzotropolones, which are inaccessible biomimetically, must be accessed by different approaches. The newest addition to such alternatives emerged from the preparation of this project. It employs the following concept: 3,4-Benzotropolone are enols of benzocycloheptadienediones. Benzocycloheptadienediones stem from hydrolyzing benzocycloheptadienedione monoketals. The latter originate from ring-closing metatheses of ortho-(2-allyl-2,2-dimethoxyacetyl)styrenes. Proceeding further we synthesized second generation 3,4-benzotropolones. To this end we introduced bromine after the metathesis step and C,C-coupled the resulting bromoolefin moieties. In detail, the synthetic chemistry of new 3,4-benzotropolones and pulvinones shall be studied in five regards: 1) Exploring the structural space of 1st and 2nd generation 3,4-benzotropolones 2) Realizing the first total synthesis of the 3,4-benzotropolone-/bispulvinone fungal dye aurantricholonee 3) Developing ring-closing metathesis routes to 3rd generation 3,4-benzotropolones, which work without an acidic hydrolysis 4) Establishing new access routes to pulvinones 5) Measuring the histone demethylase inhibitory effect of all new 3,4-benzotropolones. Our preliminary studies revealed a pertinent potential

1945年，一种羟基环甲苯酮被确定为真菌染料的核心。这个核心被命名为Tropolone。它代表了第一个无电荷的异摩西型非双苯胺芳族化合物。苯的环向Tropolone定义了3,4-和4,5-苯并蛋白的结构。我们项目的主要目的是分别多样化和任意可变替代模式的3,4-苯并群岛的合成。合成3,4-苯并蛋白是防腐剂和紫外线吸收剂，并针对微生物，逆转录病毒和肥胖作用。合成3,4-苯并酮也是治疗痤疮和败血症的铅。 theaflavin是另外3.4-苯并蛋糕，对健康有益。它源自发酵茶。在适当的术语意义上，有近40种变化存在3,4-苯并酮天然产品。它们包括一种名为Aurantricholone的真菌染料。实现该化合物的第一个总合成是我们项目的另一个目标。当我们试图通过氧化儿茶酚/pyrogallol混合物来获得它时，Aurantricholone仍然难以捉摸。例如，在一个步骤中，据称是生物含量的。发生这种故障的可能原因是，aurantricholone类似于双（pulvinone），因为它包含两个α-芳基 - 甲基γ-（芳基甲基甲基二烯）四型酸部分。后者易于氧化，甚至是自氧化，尤其是当它们的芳基是多酚时。这是从密切相关的脉冲含量中众所周知的。因此，发展苯并酮耐受性的脉搏酮合成是该项目的另一个欲望。在我们的准备研究中建立了三种此类pulvinone途径的基础。必须通过不同的方法访问替代的3,4-苯并蛋白大都市，这是无法访问的。此类项目的准备中出现了此类替代方案的最新补充。它采用以下概念：3,4-苯并酮是苯并珠二氮的烯醇。苯二甲苯二烯二酮源自水解苯二甲苯二烯二酮单击。后者起源于Ortho-（2-酰基-2,2-二甲基乙酰乙酰基）的插入环的元素。进一步进行，我们合成了第二代3,4-苯并群岛。为此，我们引入了溴化步骤和C C耦合所得的Bromoolefin部分。 In detail, the synthetic chemistry of new 3,4-benzotropolones and pulvinones shall be studied in five regards: 1) Exploring the structural space of 1st and 2nd generation 3,4-benzotropolones 2) Realizing the first total synthesis of the 3,4-benzotropolone-/bispulvinone fungal dye aurantricholonee 3) Developing ring-closing metathesis routes to第三代3,4-苯并酮，无酸性水解工作4）建立新的通道途径5）测量所有新3,4-苯并蛋白的组蛋白脱甲基酶抑制作用。我们的初步研究表明了相关的潜力

项目成果

Two-Step Synthesis of (Z)-3-Aryl-5-(arylmethylidene)butenolides by an Ivanov Reaction/Silver(I)-Catalyzed Lactonization/In Situ Dehydration Sequence

通过 Ivanov 反应/银 (I) 催化内酯化/原位脱水序列两步合成 (Z)-3-芳基-5-(芳基亚甲基)丁烯内酯

• DOI: 10.1055/s-0036-1588338
• 发表时间: 2017
• 期刊: Synthesis
• 作者: D. Hermann;D. Arican;R. Brückner
• 通讯作者: R. Brückner

Regioselective Bromination of Benzocycloheptadienones for the Synthesis of Substituted 3,4-Benzotropolones Including Goupiolone A.

苯并环庚二烯酮的区域选择性溴化用于合成取代的 3,4-苯并托酚酮（包括 Goupiolone A）

• DOI: 10.1002/chem.201700622
• 发表时间: 2017
• 期刊: Chemistry
• 作者: D. Arican;S. Braukmüller;R. Brückner
• 通讯作者: R. Brückner

6,7‐Benzotropolone Syntheses Based on Ring‐Closing Metatheses and Four‐Electron Oxidations

• DOI: 10.1002/ejoc.202000256
• 发表时间: 2020-03
• 期刊: European Journal of Organic Chemistry
• 影响因子: 2.8
• 作者: Michael Kreibich;M. Gemander;D. Peter;Dharmendra B. Yadav;C. D. de Koning;M. Fernandes;I. Green