Accessing 2-substituted piperidine iminosugars by organometallic addition/intramolecular reductive amination: aldehyde vs. nitrone route
Authors: Mirabella S., Fibbi G., Matassini C., Faggi C., Goti A., Cardona F.
Autors Affiliation: Univ Firenze, Dept Chem Ugo Schiff, Via Lastruccia 3-13, I-50019 Sesto Fiorentino, FI, Italy; CNR INO, Via N Carrara 1, Sesto Fiorentino, FI, Italy
Abstract: A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.
Journal/Review: ORGANIC & BIOMOLECULAR CHEMISTRY
Volume: 15 (43) Pages from: 9121 to: 9126
KeyWords: PHARMACOLOGICAL CHAPERONE THERAPY; LYSOSOMAL BETA-GALACTOSIDASE; NUCLEOPHILIC ADDITIONS; GAUCHER-DISEASE; STORAGE DISORDERS; HIGHLY POTENT; INHIBITORS; DESIGN; G(M1)-GANGLIOSIDOSIS; GLUCOCEREBROSIDASEDOI: 10.1039/c7ob01848gCitations: 9data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2023-03-19References taken from IsiWeb of Knowledge: (subscribers only)Connecting to view paper tab on IsiWeb: Click hereConnecting to view citations from IsiWeb: Click here