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Regio‐ and Stereoselective Biocatalytic Monoamination of a Triketone Enables Asymmetric Synthesis of Both Enantiomers of the Pyrrolizidine Alkaloid Xenovenine Employing Transaminases
Author(s) -
Payer Stefan E.,
Schrittwieser Joerg H.,
Grischek Barbara,
Simon Robert C.,
Kroutil Wolfgang
Publication year - 2016
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201500781
Subject(s) - chemistry , stereoselectivity , pyrrolizidine , enantiomer , pyrrolizidine alkaloid , diastereomer , stereochemistry , moiety , enantioselective synthesis , ketone , organic chemistry , catalysis
Abstract The (+)‐ as well as the (−)‐enantiomer of the pyrrolizidine alkaloid xenovenine were prepared within five steps with 17 and 30% overall yields, respectively, in optically pure form, >99% ee as well as >99% de . In the asymmetric key step a transaminase performed a regio‐ and stereoselective monoamination of a triketone. By employing two enantiocomplementary transaminases from Arthrobacter sp. both enantiomers were accessible. The triketone was readily prepared via two steps starting from commercially available, achiral 2‐( n ‐heptyl)furan. In the final catalytic hydrogenation step, the newly introduced chiral centre directed hydrogen addition to form preferentially the desired (5 Z ,8 E )‐diastereomer. The regio‐ and stereoselective amination of a single ketone moiety out of three allowed the performance of the shortest and highest yielding total synthesis of the bicyclic showcase pyrrolizidine alkaloid without the need for protecting strategies.