title: Design and synthesis of a transition state analogue for the Diels-Alder reaction.
abstract: This paper describes the design and synthesis of a tricationic transition state analogue (TSA 1) for the Diels-Alder reaction. TSA 1 contains a bicyclo[2.2.1]heptene ring system that mimics the boat conformation of the Diels-Alder transition state and is designed to bind tightly to antibodies, nucleic acids, and imprinted polymers by means of hydrogen bonds and salt-bridges. This paper also describes the syntheses of the Diels-Alder reaction substrates (diene 2 and dienophile 3) and a sensitive HPLC assay to monitor the formation of Diels-Alder product 4. In contrast to previously reported TSAs and dienophiles for the Diels-Alder reaction that are based upon maleimides, TSA 1 and dienophile 3 are based upon fumaramide. The fumaramide system should destabilize the initially formed boat conformer of Diels-Alder product 4 and stabilize a half-chair conformer. The conversion of the initially formed boat conformer to the half-chair conformer is designed to help prevent Diels-Alder product 4 from binding strongly to catalysts selected to strongly bind TSA 1. This feature should minimize product inhibition, which can be a problem in the catalysis of the Diels-Alder reaction.
authors.affiliation: Department of Chemistry, University of California-Irvine 92697-2025, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Arora
authors.forename: Q N
authors.initials: QN
authors.lastname: Van
authors.forename: M
authors.initials: M
authors.lastname: Famulok
authors.forename: A J
authors.initials: AJ
authors.lastname: Shaka
authors.forename: J S
authors.initials: JS
authors.lastname: Nowick
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D001643:Bridged Bicyclo Compounds; C116378:bicyclo(2.2.1)heptene