Berkelic Acid: Straightforward Analogue Synthesis and Studies of Activity Against Selected Cancer Cell Lines

(–)‐Berkelic acid is an architecturally unique secondary metabolite isolated from an extremophilic Penicillium species. In this paper, we describe a very simple protocol to construct the central core of this natural product. Using this strategy, not only (–)‐berkelic acid, but also a small library of analogues has been accessed. The key point of our protocol is a remarkable silver‐catalysed cascade reaction that allows the assembly of the core of the natural product in a single step and from two simple starting materials, a 4‐pentynol derivative and an ortho‐alkynylsalicylaldehyde. The cytotoxicity of our synthetic (–)‐berkelic acid and some analogues against two cancer cell lines, OVCAR‐3 and SSCC38, was evaluated.