A Concise Synthesis of Berkelic Acid Inspired by Combining the Natural Products Spicifernin and Pulvilloric Acid

摘要

Berkeley Pit Lake in Montana, a 30 billion gallon flooded copper mine and the largest superfund cleanup site in the United States, is an unlikely source of structurally novel natural products. Yet, this highly acidic, heavy-metal contaminated poisonous broth harbors microbial life, including an extremophilic Penicilium fungus that produces the unique tetracyclic chroman/isochroman spiroketal berkelic acid (Figure 1). This compound, isolated by Stierle et al. in 2006, was found to possess selective activity against the human ovarian cancer cell line OVCAR-3 (GI_(50) 91 nM) and moderate inhibitory activity against the matrix metalloproteinase MMP-3 (1.87 μM) and the cysteine protease caspase-1 (98 μM).