Die Pharmazie is published by IMR Press from Volume 81 Issue 1 (2026). Previous articles were published by another publisher under the CC-BY licence, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement.
Synthesis and nicotinic binding studies on enantiopure pinnamine variants with an 8-azabicyclo[3.2.1]octane moiety
S. Schwarz 1, T. Kämpchen 1, M. C. Tilotta 2, D. Gündisch 2, G. Seitz 3
Affiliations
Article Info
1 Institut für Pharmazeutische Chemie der Philipps-Universität Marburg, Marburg, Germany
2 Institut für Pharmazeutische Chemie der Rheinischen Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
3 Institut für Pharmazeutische Chemie, Marbacher Weg 6, Marburg, D-35032, Germany, Email: seitzg@mailer.uni-marburg.de
Abstract
Bioisosteric replacement of the 9-azabicyclo[4.2.1]nonane pharmacophoric element of the novel alkaloidal marine toxine pinnamine (5) by the 8-azabicyclo[3.2.1]octane moiety resulted in conformationally restricted analogues 6a and 6c of (–)-ferruginine (4). Key step in the diastereoselective synthesis of these pyranotropanes was the condensation of enantiopure ecgonine methyl ester (9) from the “chiral pool” with the lithium anion of N-tert-butylbutyraldimin and subsequent cyclisation with TFA. The potential nAChR ligands were tested for their in vitro affinity for the (α4)2(β2)3 and the α7* nAChR subtypes. Despite obvious structural similarities with the potent alkaloids pinnamine (5) and (–)-ferruginine (4) the pyranotropanes 6a and 6c exhibited distinctly lower nAChR affinities.