Synthesis of eudistomin D analogues and its effects on adenosine receptors

Abstract

Six analogues ( 1– 6) of eudistomin D, a β-carboline alkaloid from a marine tunicate Eudistoma olivaceum, were synthesized, and their affinity and selectivity for adenosine receptors A 1, A 2A, and A 3 were examined. All the synthetic compounds 1– 6 did not show affinity to the adenosine A 1 receptor. δ-Carboline 3 exhibited the most potent affinity to the adenosine receptor A 3 among compounds 1– 6. δ-Carbolines 3 and 4 showed better affinity than the corresponding β-carbolines 1 and 2, respectively, while N-methylation ( 2, 4, and 6, respectively) of the pyrrole ring in 1, 3, and 5 resulted in the reduced affinity to the adenosin A 3 receptor. On the other hand, an eudistomin D derivative, BED, exhibited modest affinity to all the receptors A 1, A 2A, and A 3 but no selectivity.