Baclofen oxidation

The y-lactone problem is made easier because the FGs are all based on oxygen. The molecule can therefore be disconnected without FGl except for oxidation or reduction. Let s now look at the synthesis of a molecule with a difficult FG the muscle relaxant baclofen TM 349. What is the difficult FG ... 

Based on the idea that pyrrolidines can be metabolized selectively to y-aminobutyric acid derivatives, Wall and Baker [189] developed a retro-metabolic approach with 3-(4-chlorophenyl)pyrrolidine (5.92, Fig. 5.25) as a prodrug for the GABA-ergic agent baclofen (5.93, Fig. 5.25). In vitro studies showed that metabolism of 5.92 yields a pair of isomeric lactam metabolites (5.94, 5.96) and a pair of isomeric amino acid metabolites (5.93, 5.95). The formation of the metabolites resulting from the oxidation... 

SCHEME 34.32. Synthesis of (—(-baclofen 124 via asymmetric Bacyer-ViUiger oxidation. 

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