Efficient Synthesis of 1-Thiomansonones with Anti-MRSA Activity

Abstract

In this study, we developed an efficient and general synthetic strategy for thiaphenalene, a sulfur-containing polyaromatic hetero-cycle, and applied for the synthesis of 1-thio derivatives of mansonone I and F, natural 1-oxaphenalenic orthoquinones. The pivotal steps for the construction of thiophenalene skeleton include formation of arylsulfide by Newman-Kwart rearrangement of thiocarbamate or palladium-catalyzed cross-coupling, and pericyclic ring closure. Three bioisosterically modified orthoquinones were synthesized and were evaluated for anti-MRSA activity.