Abstract
AbstractLeontidine and camoensine, the main representatives of the small quinolizidine‐indolizidine alkaloid subgroup, are characterized by an inner bispidine system to which a 2‐pyridone and a pyrrolidine are fused on opposite sides. We efficiently synthesized both natural products from the commercially available and abundant alkaloid cytisine, which was converted into the key intermediate, N‐Boc‐11‐oxocytisine, by iodine oxidation and protection. Grignard addition, Paal‐Knorr type cyclization, and hydrogenation delivered endo‐pyrrolidine fused leontidine, while the reversed reaction order, viz. reduction, Sakurai allylation, and ring closure, afforded exo‐pyrrolidine annulated camoensine. Hydrogenation and deoxygenation of the pyridone moieties provided four further alkaloids, tetrahydroleontidine, camoensidine, 11‐epileontidane and leontidane. In addition, the artificial alkaloid isoleontidine, carrying an endo‐fused pyrrolidine on the same side as the pyridone, was prepared from C‐13 oxidized cytisine.
Highlights
Tri- and tetracyclicquinolizidine alkaloids (Figure 1) are the most prominent secondary metabolites in the Papilionoideae subfamily of the plant family Fabaceae (Leguminosae).[1,2]. These natural products are all structurally characterized by an inner bispidine core (3,7-diazabicyclo[3.3.1]nonane, 6), to which normally combinations of an exo- or endo-piperidine, as in sparteine (1), lupanine (2), anagyrine (4), and thermopsine (5), or an oxidized version thereof, such as the 2-piperidone in 2 or the 2-pyridone in cytisine (3), 4, and 5, are attached on opposite sides
We recently presented an effective inside-out approach to tri- and tetracyclic bisquinolizidine alkaloids that permits access to more than 25 members of this class in both enantiomeric forms (Scheme 1, top).[12,13,14]
Our synthesis commenced with the search for a suitable method that permits an oxidation of the amino function in cytisine (3) to an amide
Summary
Tri- and tetracyclic (bis)quinolizidine alkaloids (Figure 1) are the most prominent secondary metabolites in the Papilionoideae subfamily of the plant family Fabaceae (Leguminosae).[1,2] These natural products are all structurally characterized by an inner bispidine core (3,7-diazabicyclo[3.3.1]nonane, 6), to which normally combinations of an exo- or endo-piperidine, as in sparteine (1), lupanine (2), anagyrine (4), and thermopsine (5), or an oxidized version thereof, such as the 2-piperidone in 2 or the 2-pyridone in cytisine (3), 4, and 5, are attached on opposite sides. The abundant, commercially available alkaloid cytisine (3), which can be isolated in good quantities from the seeds of the Golden Rain tree, Laburnum anagyroides,[15] seemed to be an ideal source
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