RESUMO
The convergent and selective preparation of (Z)-monofluoroalkene-based dipeptide isosteres from functionalized fluorosulfones as a cornerstone is described. In this approach, the N-terminal amino group is introduced by a conjugate addition reaction of phthalimide onto fluorinated vinylsulfones containing α-amino-acid side chains while the C-terminal motif is linked to the fluorovinylic peptide bond mimic via the Julia-Kocienski reaction between fluorosulfones and substituted aldehydes bearing α-amino-acid side chains.
Assuntos
PeptidomiméticosRESUMO
Study of the intramolecular aza-Michael addition reaction from an aminofluorovinylsulfone opens a new route for the synthesis of pyrrolidine derivatives. An unexpected diastereoselective cyclization reaction was observed, leading preferentially to the anti-N-benzylpyrrolidine sulfone. The resulting sulfone was reacted with aldehydes to access ß-substituted α-fluoroalkenyl pyrrolidines in one step.
RESUMO
A new series of fluoroallylamines derived from hydroxypiperidines was prepared and evaluated against various glycosidases. The short synthesis of target molecules involved the modified Julia reaction between aldehydes and functionalized fluoroaminosulfones. Biological studies revealed good and selective ß-glucosidase inhibition in the micromolar range for two compounds, while the non-fluorinated analogue of the most active compound was selective towards α-glucosidase.