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A Straightforward Synthesis of 5‐Methylaaptamine from Eugenol, Employing a 6π‐Electrocyclization Reaction of a 1‐Azatriene
Author(s) -
Heredia Daniel A.,
Larghi Enrique L.,
Kaufman Teodoro S.
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201501566
Subject(s) - chemistry , isomerization , dehydrogenation , catalysis , nitration , eugenol , total synthesis , combinatorial chemistry , derivative (finance) , methylation , medicinal chemistry , organic chemistry , stereochemistry , biochemistry , financial economics , economics , gene
Aaptamine, isolated from tropical marine sponges of the Demospongiae class, is the most prominent member of a growing family of natural products. Many aaptaminoids have been shown to have interesting biological activity. The efficient access to 5‐methylaaptamine, an unnatural analogue of aaptamine, was achieved by using economic and naturally‐occurring eugenol as the starting material. The synthesis involved the preparation of a 5‐aminoeugenol derivative through successive nitration, O ‐methylation, and nitro group reduction reactions. An Elderfield–Johnson sequence was employed to synthesize the N ‐tosyl‐5‐allyl‐7,8‐dimethoxydihydro‐1 H ‐quinolin‐4‐one ring system. A catalytic double‐bond isomerization followed by a carbonyl methoximation and 6‐π electrocyclization of the 1‐azatriene motif afforded the 2,3‐dihydro‐1 H ‐benzo[ de ][1,6]naphthyridine tricyclic intermediate, which underwent a reductive desulfonylation and catalytic dehydrogenation to afford the target product.