Dihydroseselin type pyranocumarin derivatives were synthesized based on the discovery that suksdorfin (1) was isolated from Lomatium saksdorfii as an anti-HIV agent. Compound 2 demonstrated extremely potent inhibitory activity against HIV-1 replication in H9 lymphocyte cells with an EC50 value of 0.00041 μM and therapeutic index range of > 78,049 but < 390,244.