Cyclombandakamines A(1) (I) and A(2) (2), both with an unprecedented pyrane cyclohexenone dihydrofuran sequence and six stereocenters and two chiral axes, are the first oxygen-bridged dimeric naphthylisoquinoline alkaloids. They were isolated from the leaves of an as yet unidentified Congolese Ancistrocladus species. Their stereostructures were established by spectroscopic, chemical, and chiroptical methods in combination with DFT and TDDFT calculations. They apparently originate from a cascade of oxidative cyclization reactions of open-chain naphthylisoquinoline dimers and exhibit significant antiprotozoal activities.