The oxidative dearomatization (OD) of phenols is considered one of the most interesting classical biosynthetic methods which has now been translated into a chemical tool for biomimetic/bioinspired synthesis. Therefore, the dearomatization of phenols has received much attention mainly due to the potential synthetic value of the de-aromatized product, containing a cyclic ketone framework. The cyclohexadienone is useful for further reaction(s) to provide number of different interesting chemical scaffolds that might be biological active molecules or key intermediates en route to natural products. Therefore, our work focuses on the use of oxidative dearomatization reaction to investigate a total synthesis of the tris guanidine natural product KB343 (Figure 1-A). In 2018, KB343 was isolated from the aqueous extract of a Palauan zoantharian, <i>Epizoanthus illoricatus</i>. We propose that the A&B and C&D rings (Figure 1-A) might be established via OD reactions. Therefore, we have investigated the application of OD reactions in number of phenolic thio/urea derivatives and guanidines (Figure 1-B&C). In this paper we describe the outcome of this investigation. Thioureas and guanidines afford a single dearomatization product in modest to good yields whereas, for phenolic urea compounds, C-X cyclization depends on the basicity of NAr group. Furthermore, we have designed new protected urea derivatives containing alkoxy amines instead of aniline derivatives to improve the yield and chemoselectivity. The results have met our expectation because the lone pair on the oxygen will stabilize the putative positive charge formed on the nitrogen atom of the alkoxyamino group.

Oxidative dearomatization reactions toward total synthesis of KB343

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.