3-Alkyl 1,6-dihydropyridines from 3-alkyl 5,6-dihydro-pyridinium salts. Implications in the biosynthesis of some macrocyclic marine alkaloids

Abstract

Additions of salts 1 and dihydropyridines 2 in an intramolecular manner have been invoked in the biosynthesis of some macrocyclic alkaloids such as manzamines, sarain A and halicyclamine A, recently isolated from sponges. We report conditions for the deprotonation of easily accessible salts 1, giving a regioselective entry to 3-alkyl 1,6-dihydropyridines 2. Also, we show that species 1 and 2 can be generated from a common intermediate such as 9. Dihydropyridines 2 are unstable at high temperatures giving isomeric 1,2- and 1,4-dihydropyridines, but were conveniently trapped by dienophiles to give synthetically useful isoquinuclidines such as 18 or 20.