The Diels-Alder reaction provides a general and facile entry for the synthe
sis of six-membered cyclic structures. Consequently, it has been used exten
sively by organic chemists for the construction of complex compounds with p
harmaceutical potential. Nature also appears to have utilized this reaction
in the biosynthesis of several secondary metabolites. Given its utility, v
arious catalysts have been discovered for the reaction ranging from simple
Lewis acidic transition metals to complex catalytic antibodies. More recent
ly, modified RNA has also been shown to be an effective Diels-Alderase with
a highly specific active site. The RNA Diels-Alderase activity was also sh
own to be absolutely dependent on the nature of the base modification and t
he presence of cupric ion. Together, these results suggest that this RNA Di
els-Alderase achieves a portion of its rate acceleration through Lewis acid
catalysis, a different mechanistic mode than similar protein Diels-Alderas
es. The notion that RNA can accelerate reactions through Lewis acid catalys
is suggests that modified RNA may serve as a tunable catalytic platform for
the creation of structurally diverse compounds using a variety of powerful
chemical transformations.