Design and synthesis of a transition state analogue for the Diels-Alder reaction.
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.
Arora
P S
PS
Department of Chemistry, University of California-Irvine 92697-2025, USA.
Van
Q N
QN
Famulok
M
M
Shaka
A J
AJ
Nowick
J S
JS
D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016339:Spectrometry, Mass, Fast Atom Bombardment
D001643:Bridged Bicyclo Compounds; C116378:bicyclo(2.2.1)heptene