Studies On The Total Syntheses Of (-)-Spirooliganones A And B

The thesis aims at studies on the total syntheses of natural products (-)-Spirooliganones A and B and the recent development of asymmetric oxidative dearomatizations promoted by hypervalent iodine(III) reagents. It mainly includes the following two chapters:Chapter 1:Studies on the total syntheses of natural products (-)-Spirooliganone A and (-)-Spirooliganone B.Illicium oligandrum is magnoliaceae plant from the genus Illicium. It not only can be made spices, insect repellent, raw materials of making toothpaste, cosmetics, but also in terms of medicinal value, it is often used in the traditional Chinese medicine for the treatment of rheumatoid arthritis. The research found that some chemical composition of the plants of Illicium have antiviral activity. In August 2013, Yu and co-workers, Chinese Academy of medical sciences and Peking Union Medical College, investigated the lipophilic fraction of the chloroform extract from the roots of Illicium oligandrum. Finally, two new compounds named spirooliganones A and B were isolated. Two new novel spirooliganones A and B, a rare dioxaspiro skeleton, are a pair of spiro carbon epimers. They exhibit potent activities against influenza virus A/Hanfang/359/95 (H3N2) and coxsackie virus B3 (IC50=3.70-33.33 μM). The unique molecular structures of the two new compounds and good antiviral activity attract our attention. We hope to design a simple and efficient route for synthetising two compounds that have good antiviral activity, laying the foundation for further study.On the basis of consulting a large number of literature, our group has designed a concise synthetic route of spirooliganones A and B. Our synthetic route started from commercially available 1,3-cyclohexanedione, formalin, (-)-sabinene, prenyl bromide, and allyl bromide. First of all, under the proline catalysis, a Knoevenagel/hetero-Diels Alder reaction was used to establish the tetracyclic core and a tandem oxidative dearomatization/cyclization was adopted to build the final oxa-spiro ring. It is worth nothing that we introduced the required prenyl and allyl chains through claisen rearrangement reaction at the right time, avoiding the use of any protection group in the process of the total synthese. Finally, we developed a concise and efficient route to accomplish the first enantioselective total syntheses of (-)-spirooliganones A and B in 8 steps. It should be noted that the whole studies took only ten months.Chapter 2:The methods of asymmetric oxidative dearomatizations promoted by hypervalent iodine(III) reagents (review).The use of hypervalent iodanes in the oxidative dearomatization of phenols is a general and well-established procedure for the construction of cyclohexadienone structures. Despite these reagents demonstrated a well selectivity to the functional groups, their extensive use of synthetic fields has, in part, been slowed by concerns about their ease of preparation and stability. However, hypervalent iodanes’use in asymmetric oxidative dearomatization reactions is underdeveloped. Through a large number of studies have found that employ a stoichiometric oxidant (such as mCPBA) together with catalytic amounts of an aryl iodine can renew a new kind of hypervalent iodine intermediates, which have been used in asymmetric oxidative dearomatization reactions. In recent years, several research groups have made a major breakthrough in this field. This chapter mainly discusses and summarizes the important breakthrough of asymmetric oxidative dearomatization reactions. At the same time, enumerating its deficiency. The successful recognition of an aryl iodine catalyst efficient of performing asymmetric oxidative dearomatization reactions on a large amount of phenolic compounds will not only provide deeper understanding of the reactivity and structure of hypervalent iodine intermediates, but will also be applied to the syntheses of many natural products and drugs.