Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
-Transition state mimicry is one of the most powerful concepts in enzyme inhibitor design and has led to the development of catalytic antibodies. Transition state analogs are compounds with a fixed shape that resemble the geometry and charge distribution of the transition state of a given reaction. Stabilization of a transition state like conformation is most often achieved by incorporating a ring system into the analog. We show herein that atropisomerism can be used as a new principle for enforcing a transition state like conformation. Atropisomerism relates to the existence of stereoisomers of structurally constrained molecules due to a frozen rotation about a single bond, as for example in binaphthol. The 1-aminomethylnaphthalene derivative 1 exhibits atropisomerism due to a frozen rotation about the C(1)-C(methylene) single bond, which holds the dihedral angle θ[C(2)-C(1)-C(methylene)-N] close to 90°. Compound 1 mimics the transition state for hydride transfer between 1,4-dihydroquinolines 4 and acetone.
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