Pyrrolizidines, indolizidines and quinolizidines via a double reductive cyclisation protocol: concise asymmetric syntheses of (+)-trachelanthamidine, (+)-tashiromine and (+)-epilupinine

Journal article

The asymmetric syntheses of pyrrolizidine, indolizidine and quinolizidine alkaloids have been achieved using the diastereoselective conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to α-alkenyl-α,β-unsaturated esters followed by diastereoselective protonation of the resultant enolates as the key stereodefining steps. The azabicyclic scaffolds were then efficiently constructed upon sequential oxidative cleavage of the olefinic units within the resultant β-amino esters and hydrogenolytic N-debenzylation of the corresponding dialdehydes, which occurs with concomitant double reductive cyclisation. Subsequent reduction of the ester moieties with LiAlH4 gave (+)-trachelanthamidine, (+)-tashiromine, (1S,8aR)-1-(hydroxymethyl)octahydroindolizine and (+)-epilupinine in 4.9, 4.1, 3.0 and 5.9% overall yield, respectively, in only six steps from commercially available starting materials.

Authors: Brambilla, M; Davies, S; Fletcher, A; Roberts, P; Thomson, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Tetrahedron
• Volume: 72
• Issue: 47
• Pages: 7417-7429
• Publication date: 2016-09-07
• Acceptance date: 2016-09-05
• DOI: 10.1016/j.tet.2016.09.006
• EISSN: 1464-5416
• ISSN: 0040-4020
• Keywords: (+)-Tashiromine; (+)-Trachelanthamidine; (+)-Epilupinine; asymmetric synthesis; azabicyclic alkaloids