Total Synthesis and Structural Reassignment of (+)-Dictyosphaeric Acid A: A Tandem Intramolecular Michael Addition/Alkene Migration Approach

摘要

Given the recent increase in bacterial resistance, the search for new and more effective antibiotics is an ever-pressing concern. The polyketide-derived natural products (+)-dic-tyosphaeric acid A and (+)-dictyosphaeric acid B were isolated by Ireland and co-workers in 2004 from a fungal isolate (F01V25) obtained from the green alga Dictyosphaeria versluyii. Interestingly, when screened for biological activity, (+)-dictyosphaeric acid A exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium, and Candida albicans. In marked contrast, (+)-dictyosphaeric acid B (2) did not exhibit any significant antibacterial activity, which presumably indicates the importance of the α,β-unsaturated ketone in the pharmacophore of dictyosphaeric acid A.