Enantioselective Synthesis of Cis-Decahydroquinoline Alkaloids

16 December 2013
12:00 pm

1 hour

Mercedes Amat

Laboratory of Organic Chemistry Faculty of Pharmacy,
Universitat de Barcelona, Spain

Host: Maria Santos
Amphiteather B,
Faculdade de Farmácia da Universidade de Lisboa,
Av. Professor Gama Pinto
1649-003 Lisboa

The cis-decahydroquinoline (cis-DHQ) system constitutes a key structural framework occurring in a variety of both natural and synthetic bioactive compounds. The most abundant source of cis-DHQ alkaloids is found in the skin secretions of neotropical dart poison frogs. Additionally, the eight cis-DHQ members of the lepadin family have been isolated from various marine natural sources. However, the DHQ motif is rare in plant sources, being restricted to Lycopodium and Nitraria species. Due to the wide range of biological activities displayed by many of these derivatives and their ability to act as a testing ground for new synthetic methods, DHQs have attracted considerable attention from organic chemists over the years. Nevertheless, the number of synthetic methodologies reported in the literature for the efficient enantio- and stereoselective construction of this azabicycle with substituents at the carbocyclic ring is still limited.

In recent work we have explored cyclocondensation reactions between chiral aminoalcohols and cyclohexanone- or 2-cyclohexenone derivatives having a propionate chain at C-2, stereoselectively leading to tricyclic lactams bearing up to four stereocenters of well-defined absolute configuration. The synthetic potential of these chiral tricyclic lactams as precursors for the preparation of cis-DHQ alkaloids will be discussed.