Synthesis of deuterated naproxens

Abstract

A general scheme for the synthesis of (S)-6-methoxy-2-propanoic acid (naproxen) deuterated on the naphthyl ring, methoxy group, or both, is described. The resulting labeled naproxen derivatives are useful probes for examining atypical kinetics displayed by cytochrome P450 2C9.

Deuteration and Tritiation of Pharmaceuticals by Non-Directed Pd Catalyzed C–H Activation in Heavy and Super-Heavy Water

“…With optimized conditions for our test substrate in hand, we began by applying our deuteration protocol to nonsteroidal antiinflammatory drugs (NSAID, Scheme 2), a class of pharmaceuticals is extensively utilized to alleviate pain associated with various conditions, particularly arthritis. We first tested the deuteration of ibuprofen-OMe 1 and ketoprofen-OMe 2 which led to the corresponding deuterated products 1 30 Loxoprofen-OMe 7, which features a cyclopentyl core, exhibited noteworthy deuterium incorporation not only in the aromatic core but also in the alkyl protons adjacent to the α-keto position. This observation suggests the involvement of an acid/base-type mechanism.…”