title: Chemoenzymatic synthesis of all four diastereomers of 2,6-disubstituted piperidines through stereoselective monoamination of 1,5-diketones.
abstract: The regioselectivity of various enantiocomplementary ω-transaminases was evaluated for the stereoselective monoamination of designated 1,5-diketones; excellent conversions, enantio- and regioselectivities were observed. The resulting amino-ketones underwent spontaneous intramolecular ring closure to afford Δ1-piperideines, which served as precursors for the cis- and anti-piperidine scaffold as demonstrated for the synthesis of the alkaloids dihydropinidine and epi-dihydropinidine. Key to the success of accessing the trans-piperidines was a Lewis acid mediated conformational change of the Δ1-piperideines in the reduction step. Thus, all four diastereomers of 2,6-disubstituted piperidines could successfully be prepared.
authors.affiliation: ACIB GmbH, c/o Heinrichstrasse 28, A-8010 Graz, Austria.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Simon
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Zepeck
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kroutil
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D000586:Amination; D007659:Ketones / Q000737:chemistry*; D058116:Lewis Acids / Q000737:chemistry*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D000637:Transaminases / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D007659:Ketones; D058116:Lewis Acids; D010880:Piperidines; D000637:Transaminases