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Asymmetric Construction of Alkaloids by Employing a Key ω‐Transaminase Cascade
Author(s) -
Taday Freya,
Ryan James,
Argent Stephen P.,
Caprio Vittorio,
Maciá Beatriz,
O'Reilly Elaine
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202000067
Subject(s) - isopropylamine , cascade reaction , transaminase , intramolecular force , yield (engineering) , chemistry , michael reaction , cascade , phthalide , annulation , combinatorial chemistry , organic chemistry , catalysis , enzyme , materials science , chromatography , metallurgy
An ω‐transaminase‐triggered intramolecular aza‐Michael reaction has been employed for the preparation of cyclic β‐enaminones in good yield and excellent enantio‐ and diastereoselectivity, starting from easily accessible prochiral ketoynones and commercially available enzymes. The powerful thermodynamic driving force associated with the spontaneous aza‐Michael reaction effectively displaces the transaminase reaction equilibrium towards product formation, using only two equivalents of isopropylamine. To demonstrate the potential of this methodology, this biocatalytic aza‐Michael step was combined with annulation chemistry, affording unique stereo‐defined fused alkaloid architectures.