A combination of parallel chemical synthesis and biocatalysis has been used to prepare and amplify a library of cross-conjugated cyclopentenones. A number of marine and terrestrial natural products with antibiotic activity are known to incorporate this pharmacophore. The library was screened for anticancer, antimycobacterial, antifungal, and antibacterial activity. The positive results from the screens provide an indication of the structural features that are associated with activity in the various assays and suggest promising avenues for further inquiry.