Total syntheses of isonaamine C and isonaamidine E

Abstract

The total syntheses of two alkaloids isolated from a marine sponge of the Leucetta sp. have been accomplished in 6 and 7 steps starting from a 4,5-diiodoimidazole derivative. Grignard mediated halogen-metal exchange was used to install the benzyl side chain. C2 substitution was accomplished via lithiation followed by quenching with trisyl azide which provided isonaamine C after hydrogenation. Isonaamidine E was then prepared from isonaamine C via introduction of the hydantoin ring by reaction with an activated parabanic acid.

Total synthesis and cytotoxicity of Leucetta alkaloids

“…24 In this subfamily, the imidazole nitrogen is substituted with a benzyl moiety and thus the synthesis commenced with the 4,5-diiodoimidazole by alkylation with p -methoxybenzyl chloride resulting in the formation of 22 (Scheme 2). Treatment of 22 with ethylmagnesium bromide followed by quenching with water provided the 4-iodoimidazole 23 .…”

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

“…399 The antitumor activity as well as the structure−activity relationship of naamidine A was studied, notably by the synthesis of thiazole analogues. 400 The syntheses of clathridine A 401 as well as other analogs of naamidine A such as naamidine G and 14methoxynaamidine G, 402 naamidine H, 403 and isonaamidine E 404 were reported by Lovely's group. Their strategy relied on the synthesis of the 2-aminoimidazole moiety by substitution of 1methyl-4,5-diiodoimidazole, the difference between the analogues being mainly the nature of the substituents on the benzyl ring(s).…”

Muscarine, imidaozle, oxazole and thiazole alkaloids

“…A concise total synthesis of two spongederived alkaloids isonaamine C 69 and isonaamidine E 70 has been accomplished starting from 4,5-diiodoimidazole. 66 A total synthesis of 7 0 -desmethylkealiiquinone 71 has been recently completed featuring an intramolecular Diels-Alder reaction of an imidazole-containing enyne and conversion of the phthalaldehyde derivative to the dihydroxybenzoquinone catalyzed by KCN. 67 The direct conversion of imidazolium slats to the corresponding 2-imidazolone or 2-iminoimidazole derivatives, the key blocks of 2-aminoimidazole alkaloids, has been achieved by treatment of the salt with commercial bleach.…”