Design and synthesis of a transition state analogue for the Diels-Alder reaction

Paramjit Arora, Que N. Van, Michael Famulok, A. J. Shaka, James S. Nowick

Research output: Contribution to journalArticle

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. Copyright (C) 1998 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1421-1428
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume6
Issue number9
DOIs
StatePublished - Sep 1998

Fingerprint

Cycloaddition Reaction
Ships
Boats
Maleimides
Catalysis
Nucleic Acids
Conformations
Hydrogen
Assays
Hydrogen bonds
Polymers
Salts
High Pressure Liquid Chromatography
Catalysts
thymic shared antigen-1
Antibodies
Substrates
fumaramide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Design and synthesis of a transition state analogue for the Diels-Alder reaction. / Arora, Paramjit; Van, Que N.; Famulok, Michael; Shaka, A. J.; Nowick, James S.

In: Bioorganic and Medicinal Chemistry, Vol. 6, No. 9, 09.1998, p. 1421-1428.

Research output: Contribution to journalArticle

Arora, Paramjit ; Van, Que N. ; Famulok, Michael ; Shaka, A. J. ; Nowick, James S. / Design and synthesis of a transition state analogue for the Diels-Alder reaction. In: Bioorganic and Medicinal Chemistry. 1998 ; Vol. 6, No. 9. pp. 1421-1428.
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