A new dimeric alkaloid plakoramine A [(+/-)-1] was identified from a marine sponge Plakortis sp. Chiral-phase HPLC separation of (+/-)-1 led to the purified enantiomers (+)-1 and (-)-1 which both potently inhibited CBL-B E3 ubiquitin ligase activities. The absolute configurations of the enantiomers were determined by quantum chemical calculations. Scrutinization of the purification conditions revealed a previously undescribed, nonenzymatic route to form (+/-)-1 via photochemical conversion of its naturally occurring monomeric counterpart, plakinidine B (2).