The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids : A Modular "Inside-Out" Approach

Title data

Scharnagel, Dagmar ; Goller, Jessica ; Deibl, Nicklas ; Milius, Wolfgang ; Breuning, Matthias:
The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids : A Modular "Inside-Out" Approach.
In: Angewandte Chemie International Edition. Vol. 57 (2018) Issue 9 . - pp. 2432-2435.
ISSN 1521-3773
DOI: https://doi.org/10.1002/anie.201712852

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Abstract in another language

Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7-diazabicyclo[3.3.1]nonane) to which combinations of an α,N-fused 2-pyridone, an endo- or exo-α,N-annulated piperidin(on)e, and an exo-allyl substituent are attached. We developed a modular “inside-out” approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C2-symmetric 2,6-dioxobispidine by desymmetrization of a 2,4,6,8-tetraoxo precursor, the construction of the α,N-fused 2-pyridone by using an enamine-bromoacrylic acid strategy, and the installation of endo- or, optionally, exo-annulated piperidin(on)es.