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

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• 作者：Wang ; Guijun ; Hollingsworth ; Rawle I.
• 刊名：Tetrahedron: Asymmetry
• 出版年：1999
• 出版时间：May 21, 1999
• 年：1999
• 卷：10
• 期：10
• 页码：1895-1901
• 全文大小：93.6 K

文摘

(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.