Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold

Abstract

A general synthetic route to the unknown 1,3‐dicarbonyl tropane derived curcumin analogues was developed. The method was based on the aldol condensation reaction (40–90 % yield, two steps without product isolation) and acylation of the resulting 2‐benzylidenetropinones with substituted cinnamoyl cyanides (yields 41–91 %). Overall 18 new tropane derivatives featuring the characteristic curcuminoid hepta‐1,6‐dien‐3,5‐dione structure were synthesized and characterized. The range of the substituted aromatic rings in the prepared analogues included Ph, m‐MeO‐C6H4, 3,4‐di‐MeO‐C6H3, 3,4,5‐tri‐MeO‐C6H2, p‐Br‐C6H4, p‐F‐C6H4, p‐CF3‐C6H4, p‐NO2‐C6H4, 2‐NO2‐4,5‐di‐CH3O‐C6H2, 2‐NO2‐4,5‐O‐CH2‐O‐C6H2, 3‐MeO‐4‐[CH(CH3)‐OEt]‐C6H3, 3‐MeO‐4‐OH‐C6H3, p‐MeO‐C6H4, 4,5‐O‐CH2‐O‐C6H3, 3‐MeO‐4‐MeOCOO. Two orthogonal protective groups for hydroxyl (acetal or carbonate), removable in acidic or basic conditions, were used for synthesizing curcuminoids with free phenolic groups (3‐MeO‐4‐OH‐C6H3).