title: Concise Chemoenzymatic Three Step Total Synthesis of Isosolenopsin Through Medium Engineering.
abstract: A short and efficient total synthesis of the alkaloid isosolenopsin and its enantiomer has been achieved. In the key step, a ω-transaminase catalyzed the regioselective mono-amination of the diketone pentadecane-2,6-dione which was obtained in a single step via Grignard reaction. Initial low conversions in the biotransformation could be overcome by optimisation of the reaction conditions employing suitable cosolvents. In the presence of 20 vol% DMF orn-heptane best results were obtained employing two enantio-complementary ω-transaminases originating fromArthrobacterbetween 30-40 °C; under these conditions conversions of >99% and perfect stereocontrol (ee> 99%) were achieved. Diastereostelective chemical reduction (H2/Pd/C) of the biocatalytic product gave the target compound. The linear three step synthesis provided the natural product isosolenopsin in diastereomerically pure form (ee> 99%, d.r. = 99:1) with an overall yield of 64%.
authors.affiliation: ACIB GmbH, Heinrichstraße 28, 8010-Graz, Austria.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Simon
authors.affiliation: ACIB GmbH, Heinrichstraße 28, 8010-Graz, Austria.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Institute of Chemistry, Organic and Bioorganic Chemistry, Heinrichstraße 28, Karl-Franzens University, 8010-Graz, Austria.
authors.forename: Horst
authors.initials: H
authors.lastname: Lechner
authors.affiliation: Sandoz GmbH, Biocatalysis Lab, Biochemiestraße 10, 6250-Kundl / Tirol, Austria.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Zepeck
authors.affiliation: Institute of Chemistry, Organic and Bioorganic Chemistry, Heinrichstraße 28, Karl-Franzens University, 8010-Graz, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kroutil
keywords: alkaloids; diastereoselectivity; piperidines; reductive amination; ω-transaminases