Total Syntheses of Naamine A and Naamidine A, Marine Imidazole Alkaloids

The first total syntheses of naamine A (4) and naamidine A (5), marine imidazole alkaloids, were achieved through twelve and thirteen steps of reactions, respectively, starting from 1-methyl-2-phenylthio-1H-imidazole (17).Recently, many marine imidazole alkaloids such as 1 -10 in Table 1 have been isolated from sponges, and their antitumour and antibacterial activities have been also found. 1,2Structural characteristics of these alkaloids are that one or two alkoxybenzyl group(s) locates at the 1-, 4-and/or 5-positions of the 1H-imidazole ring and the 2-position is substituted with a primary amino group or a (1-methyl-2,5-dioxo-3-imidazolin-4-yl)amino moiety 2 (Table 1).Hitherto, we have reported the total synthesis of several marine imidazole alkaloids such as nortopsentins A -D, 3 topsentin, 4 kealiiquinone (10), 5 and clathridine A (2). 6 In this paper, we would like to report the first total syntheses of naamine A (4) and naamidine A (5) starting from 1-methyl-2-phenylthio-1H-imidazole (17).In previous papers, we reported a procedure for the preparation of 2-aminoimidazoles and preclathridine A (2) by using a reaction of 2-bromoimidazole with sodium azide or trimethysilyl azide (TMSN 3 ) in the N N H N O O CH 3 CH 2 OH CH 2 OCH 3 CH 2 O O CH 2 OCH