Daphneodorins A-C, Anti-HIV Gnidimacrin Related Macrocyclic Daphnane Orthoesters from Daphne odora

Three novel gnidimacrin related macrocyclic daphnanes (GMDs), daphneodorins A-C (2-4), were isolated from Daphne odora Thunb., together with gnidimacrin (1). Their structures were established by extensive physicochemical and spectroscopic analyses. Compounds 2 and 3 potently inhibited HIV-1 replication at subnanomolar concentrations (EC₅₀ 0.16 and 0.25 nM, respectively). Compounds 2-4 represent a novel type of GMDs that are highly oxygenated on the macrocyclic ring, suggesting good potential for anti-HIV drug development by further chemical modification.