STEREOCONTROLLED SYNTHESIS OF (+/-)-DEBROMOAPLYSIN, (+/-)-APLYSIN, (+/-)-DEBROMOAPLYSINOL, (+/-)-APLYSINOL, AND (+/-)-ISOAPLYSIN

Stereocontrolled synthesis in racemic form of the title marine sesquiterpenes is described. Alkylation of styrenol 6 with a-bromopropanoic acid furnished acid 7. Similar alkylation with α-bromo-β-methoxypropanoic acid provided acid 8. Intramolecular cycloaddition of the ketene generated from the acid chloride of 7 afforded cyclobutanone 9 whereas 8 led to a mixture of 10 and 11, but following a modified condition 10 could be obtained exclusively. Regioselective ring expansion of 9 and 10 to cyclopentanones 13 and 15 followed by addition of methylmagnesium iodide and dehydration provided olefins 16 and 17. Hydrogenation of these using Pd-C catalyst lacked selectivity, but Pt02 showed selectivity, affording (±)-2 and 19, respectively. Controlled bromination of 2 furnished (±)-aplysin (1), and 19 yielded 21. Demethylation of 19 afforded (±)-debromoaplysinol (3). Similarly 21 furnished (±)-aplysinol (4). Bromination of 3 resulted in (±)-isoaplysin (5). © 1990, American Chemical Society. All rights reserved.