Diels-Alderase: Myth or Reality!
The Diels-Alder (DA) reaction is one of the most common types of cycloaddition reaction which leads to the formation of six-membered ring. The DA reaction plays a pivotal role in the synthesis of diverse polymer and natural products. However, the mechanism through which the DA reaction occurs makes it difficult to elucidate experimentally but can be fully addressed in silico. The DA reaction has found its applications in several aspects of chemistry and it has also been proposed as a key transformation in the biosynthesis of many cyclohexene-containing secondary metabolites. For instance, the key step in the biosynthesis of spinosyn A is a DA reaction which converts the putative macrocyclic lactone into the tricyclic compound (Figure 1) which may be catalyzed by an enzyme. In order to confirm this hypothesis, it is mandatory to demonstrate the concertedness of the transition state and thus, the enzyme would be known as Diels-Alderase. We have used computational methods to locate and characterize the transition state by making use of a theozyme, also known as theoretical enzyme.
Figure 1: Cyclisationreaction.
This presentation describes the fundamentals of cycloaddition and DA reactions. This is followed by our sustained efforts to understand these reactions using model systems and then culminating to an enzyme-catalysed reaction.