Synthesis of Tetrahydrolipstatin and Tetrahydroesterastin, Compounds with a β-Lactone Moiety. Stereoselective Hydrogenation of a β-Keto δ-Lactone and Convertion of the δ-Lactone into a β-Lactone

Article abstract of DOI:10.1021/jo00241a018

Stereoselective syntheses of tetrahydrolipstatin (1) and tetrahydroesterastin (2) are described.The key intermediate β-ketoδ-lactone 7 is hydrogenated stereoselectively to yield hydroxy δ-lactone 9, which is transformed into hydroxy β-lactone 10.Esterification of 10 with (S)-N-formylleucine under Mitsunobu's conditions yields tetrahydrolipstatin (1).Esterification of 10 with (S)-N-acetylasparagine under the same conditions yields 17 (mixture of two diastereomers), which gives by saponification hydroxy β-lactone 18.Reaction of the latter with the mixed anhydride of (S)-N-Z-asparagine, hydrogenation, and acetylation give tetrahydroesterastin (2).