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Synthetic routes to l-carnitine and l-gamma-amino-beta-hydroxybutyric acid from (S)-3-hydroxybutyrolactone by functional group priority switching

1999; Elsevier BV; Volume: 10; Issue: 10 Linguagem: Inglês

10.1016/s0957-4166(99)00169-x

1362-511X

Guijun Wang, Rawle I. Hollingsworth,

Amino Acid Enzymes and Metabolism

(R)-3-Hydroxy-4-trimethylaminobutyric acid (l-carnitine) and (R)-4-amino-3-hydroxybutyric acid (GABOB) are two compounds with a very high level of medical significance. They can be prepared from (R)-3-hydroxy-γ-butyrolactone which is not readily available in significant quantities. The corresponding (S)-lactone is available in large quantities but attempts at inverting the stereochemistry of the hydroxyl group lead to elimination to give the furanone. Here we describe a straightforward route to these two compounds, starting from (S)-3-hydroxy-γ-butyrolactone by adding a highly oxidized carbon at one end whilst removing one carbon from the other, thus switching the functional group priorities. In this method, the lactone is transformed to an (R)-4-cyano-3-hydroxybutyric acid ester which is then converted to an acyl hydrazide by treatment with hydrazine. This stable, crystalline hydrazide has not been described before. It is readily converted to (R)-4-amino-3-hydroxybutyronitrile, a precursor of l-carnitine and GABOB, by Curtius rearrangement under conditions that do not result in deamination.