Synthesis of Bisanthraquinone Natural Product and BINOL-type Chiral Ligands

双蒽醌天然产物和联醇型手性配体的合成

• 批准号: 8330757
• 负责人: Erin Eileen Podlesny
• 金额: $ 2.54万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330757
• 关键词: Acetals; Affect; Alder plant; Antioxidants; BINOL; Biocompatible Materials; Biological; Biological Factors; Catalysis; Chemistry; Complex; Coupling; Development; Diabetes Mellitus; Diels Alder reaction; Disease; Effectiveness; Electrons; Generations; Goals; Health; Hepatitis; High Pressure Liquid Chromatography; Ligands; Mental Depression; Methods; Naphthols; Parents; Pharmaceutical Chemistry; Pharmacologic Substance; Property; Public Health; Quinones; Reaction; Reporting; Research; Route; Skin; Structure; Therapeutic Agents; Ultraviolet Rays; analog; cancer therapy; cell growth; enantiomer; ketene; neoplastic cell; oxidation; physical property

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.

本项目将合成一组未被合成的轴手性双蒽醌类天然产物，为生物学研究提供材料。据报道，其中一些化合物的生物活性和物理特性影响各种公共卫生问题，包括治疗癌症（抑制肿瘤细胞生长）、[7]糖尿病、[8]肝炎、[9]和抑郁症此外，据报道，其抗氧化性能可能有助于保护皮肤免受紫外线辐射的影响尽管如此，许多双蒽醌类药物的活性仍然缺乏大量的信息，理由是需要更多的生物学研究。这些分子的有效合成是实现这些目标的关键。具体地说，化合物的生成将通过从相同的手性双萘醌中间体发散的协同合成来实现（1a）。这种多功能双萘醌中间体将由2-萘酚通过对映选择性氧化联芳偶联反应合成，然后氧化为1。1a和各种乙烯基酮缩醛(2)之间的串联diel - alder /芳构化反应将产生双蒽醌结构，随后的转化将产生天然产物（3-7）。