Neocyclomorusin (<b>1</b>), a natural bioactive pyranoflavone mainly isolated from plants of the Moraceae family, was synthesized for the first time using a Friedel-Crafts reaction, a Baker-Venkataraman (BK-VK) rearrangement, a selective epoxidation, and a novel S<sub>N</sub>2-type cyclization as the key steps. The present protocol was also successfully applied for the total synthesis of oxyisocyclointegrin (<b>2</b>). Structurally related natural products morusin (<b>23</b>) and cudraflavone B (<b>24</b>) were also prepared. We investigated the antibacterial activities of these natural compounds against both Gram-negative and Gram-positive strains. The prenylated flavones, morusin (<b>23</b>) and cudraflavone B (<b>24</b>), showed comparable activity to ampicillin and kanacycin A against <i>Staphylococcus aureus</i>. Both morusin (<b>23</b>) and cudraflavone B (<b>24</b>) showed better antibacterial activities than ampicillin against the Gram-positive bacteria <i>Staphylococcus epidermidis</i> and <i>Bacillus subtilis</i>. Both neocyclomorusin (<b>1</b>) and oxyisocyclointegrin (<b>2</b>) displayed disappointing antimicrobial activities against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, and <i>Bacillus subtilis</i> strains.