Leveraging Alumina-Templated

Abstract

The work disclosed in this dissertation outlines a newly discovered acidic alumina-mediated orthoallylation of unprotected phenols and the application of this method to the synthesis of prenylated phenolic natural products including dorsmanin A and hyperbeanol Q. Chapter 1 consists of a literature review of prenylated phenolic compounds and includes a discussion of their biological significance followed by an extensive review of the various synthetic strategies that have been used to prepare them. It is our intention to publish the content of this chapter as a review article for the synthetic chemistry community. Showcased in Chapter 2 is the optimization of a novel prenylation method via acidic alumina as the promoter. Phenols and allyl alcohols are combined with acidic alumina in 1,2-dichloroethane or acetonitrile to induce a proposed coordination of the substrates to the alumina surface via hydrogen bonding which facilitates the regioselective ortho-prenylation of phenols. The extensive substrate scope of this chemistry is discussed. In Chapter 3, this alumina-mediated prenylation is applied to the syntheses of several acylphloroglucinol natural products and unnatural structural analogues which are evaluated for their antimicrobial and anthelmintic (anti-parasitic) activity. Some of these compounds exhibited antimicrobial activity and some exhibited anthelmintic potential. In Chapter 4, this prenylation strategy is further extended to the syntheses of additional prenylated phenolic natural products: (±)-sanjuanolide and dorsmanin A. Investigations towards the synthesis of HP1 are also reported. Development of the syntheses of these natural product targets provides a useful venue to investigate the scope of our alumina-mediated phenol prenylation chemistry and to identify its scope and limitations.