Venlafaxine, an antidepressant, was found to be metabolically unstable. The Medicinal Chemistry team then decided to deuterate the methyl hydrogens as shown below, a strategy which successfully delivered a more stable deuterated analogue (see the transformation below). Using your knowledge of reaction kinetics, explain why such a subtle change resulted in a significantly metabolically stable analogue. OH OH CH3 CD3 H₂CO D₂CO Venlafaxine (antidepressant) CH3 CD3 Nonadeuterovenlafaxine (antidepressant)

Venlafaxine, an antidepressant, was found to be metabolically unstable. The Medicinal Chemistry team then decided to deuterate the methyl hydrogens as shown below, a strategy which successfully delivered a more stable deuterated analogue (see the transformation below). Using your knowledge of reaction kinetics, explain why such a subtle change resulted in a significantly metabolically stable analogue. OH OH CH3 CD3 H₂CO D₂CO Venlafaxine (antidepressant) CH3 CD3 Nonadeuterovenlafaxine (antidepressant)

Organic Chemistry

9th Edition

ISBN:9781305080485

Author:John E. McMurry

Publisher:John E. McMurry

Chapter16: Chemistry Of Benzene: Electrophilic Aromatic Substitution

Section16.SE: Something Extra

Problem 62AP

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