Photochemical Dimerization of Plakinidine B Leads to Potent Inhibition of the E3 Ubiquitin-Protein Ligase CBL-B.

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 ).