Synthesis of Bisanthraquinone Natural Product and BINOL-type Chiral Ligands

该项目将导致一组轴向手性双蒽醌天然产物的全合成。 这是以前没有合成过的，为生物学研究提供了材料。已报道的生物学 其中一些化合物的活性和物理性质影响各种公共卫生问题，包括 治疗癌症(抑制肿瘤细胞生长)、糖尿病、肝炎、抑郁症。 据报道，抗氧化剂的特性可能会保护皮肤免受 紫外线辐射。[12]尽管如此，许多此类双蒽醌化合物的活性缺乏大量信息， 理由是需要进行更多的生物学研究。有效地合成这些分子是实现这些目标的关键 目标。具体地说，化合物的生成将通过不同的协调合成来实现 从相同的手性双萘醌中间体(1a)中分离得到。这种用途广泛的双对苯二酚中间体 以2-萘酚为原料，经对映选择性氧化联芳基偶联反应合成 氧化成1.1a与各种乙烯基缩酮缩醛之间的串联Diels-Alder/芳构化反应(2) 提供双蒽醌结构和随后的转化将得到天然产物(3-7)。 此外，一类新的BINOL型手性配体(8a-b)将从一个更简单的 双萘酚前体(1b)。这些配体的合成很重要，因为它们可以 冲击不对称催化。催化不对称合成对科学研究很重要，因为它 为合成中的结构控制提供了一种重要手段。一种特定对映体的合成 非对映异构体在药物化学和材料化学中都很重要，因为特定的 治疗剂可能具有不同的生物活性，或者材料可能具有不同的性质。跟随 通过核磁共振和高效液相色谱对这些分子的稳定性进行分析，评估它们在 不对称催化将被探索。具体地说，这些BINOL类似物将与BINOL，H{8}- BINOL、全氟BINOL和其他电子缺陷型BINOL的产率和对映体过量比较 在各种已知的反应中。其他更受阻碍的衍生品(从苯醌部分延伸而来)也将 被合成和分析。

This project will result in total synthesis of a group of axially chiral bisanthraquinone natural products that has not been synthesized previously, providing material for biological study. The reported biological activity and physical properties of some of these compounds affects a variety of public health issues including treatment of cancer (suppression of tumor cell growth),[7] diabetes,[8] hepatitis,[9] and depression.[10] Also, antioxidant properties have been reported, which may have potential in protecting skin against the effects of UV radiation.[12] Still, a great deal of information is lacking for the activity of many of these bisanthraquinones, citing a need for more biological studies. An efficient synthesis of these molecules is central to achieving these goals. Specifically, the generation of the compounds will be achieved via a concerted synthesis that diverges from the same chiral bisnaphthoquinone intermediate (1a). This versatile bisnapththoquinone intermediate will be synthesized from a 2-naphthol via an enatioselective oxidative biaryl coupling reaction, followed by oxidation to 1. Tandem Diels-Alder/aromatization reactions between 1a and various vinyl ketene acetals (2) will provide the bisanthraquinone structure and subsequent transformations will afford natural products (3-7). In addition, a new class of BINOL-type chiral ligands (8a-b) will be generated from a simpler bisnaphthoquinone precursor (1b). The synthesis of these ligands is important because they could positively impact asymmetric catalysis. Catalytic asymmetric synthesis is important to scientific research because it provides an important means of structural control in synthesis. The synthesis of a specific enantiomer or diastereomer is important in both pharmaceutical and materials chemistry because enantiomers of a particular therapeutic agent may have dissimilar biological activity or materials may have different properties. Following analysis of the stability of these molecules via NMR and HPLC, assessment of their effectiveness in asymmetric catalysis will be explored. Specifically these BINOL analogs will be compared to BINOL, H{8}- BINOL, perfluoro-BINOL and other electron deficient BINOLs via comparison of yield and enantiomeric excess in a variety of known reactions. Other more hindered derivatives (extended from the quinone moiety) will also be synthesized and analyzed.