Computational Investigation of the Mechanism of Diels–Alderase PyrI4
Yike Zou, Song Yang, Jacob N. Sanders, Wei Li, Peiyuan Yu, Hongbo Wang, Zhijun Tang, Wen Liu, K. N. Houk
Abstract
We studied the mechanisms of activation and stereoselectivity of a monofunctional Diels-Alderase (PyrI4)-catalyzed intramolecular Diels-Alder reaction that leads to formation of the key spiro-tetramate moiety in the biosynthesis of the pyrroindomycin family of natural products. Key activation effects of PyrI4 include acid catalysis and an induced-fit mechanism that cooperate with the unique "lid" feature of PyrI4 to stabilize the Diels-Alder transition state. PyrI4 enhances the intrinsic Diels-Alder stereoselectivity of the substrate and leads to stereospecific formation of the product.
Topics & Concepts
ChemistryStereoselectivityMoietyStereospecificityIntramolecular forceStereochemistryCatalysisNatural productSubstrate (aquarium)Organic chemistryGeologyOceanographyMicrobial Natural Products and BiosynthesisChemical synthesis and alkaloidsBioactive Compounds and Antitumor Agents