A Straightforward Synthesis of 5-Methylaaptamine from Eugenol, Employing a 6ð-Electrocyclization Reaction of a 1-Azatriene

HEREDIA, D.A.; LARGHI, E. L.; KAUFMAN, T. S.

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2016 p. 1397 - 1404

1434-193X

Aaptamine,isolated from tropical marine sponges of the Demospongiae class, is the mostprominent member of a growing family of natural products. Many aaptaminoidshave been shown to have interesting biological activity. The efficient accessto 5-methylaaptamine, an unnatural analogue of aaptamine, was achieved by usingeconomic and naturally-occurring eugenol as the starting material. Thesynthesis involved the preparation of a 5-aminoeugenol derivative throughsuccessive nitration, O-methylation, and nitro group reductionreactions An Elderfield?Johnson sequence was employed to synthesize the N-tosyl-5-allyl-7,8-dimethoxydihydro-1H-quinolin-4-one ring system. Acatalytic double-bond isomerization followed by a carbonyl methoximation and 6-ð electrocyclization of the 1- azatrienemotif afforded the 2,3-dihydro-1H-benzo[de]- [1,6]naphthyridine tricyclicintermediate, which underwent a reductive desulfonylation and catalyticdehydrogenation to afford the target product.