Total Syntheses of (+)-Acutiphycin and (+)-trans-20,21-Didehydroacutiphycin

摘要

In 1984, Moore and co-workers reported the isolation and characterization of the architecturally novel macrolides (+)-acutiphycin (1) and (+)-trans-20,21-didehydroacutiphycin (2). Both compounds exhibited significant antineoplastic activity in vivo against murine Lewis lung carcinoma and cytotoxicity against the KB and NIH/3T3 cell lines. The natural source, the blue-green alga Osillatoria acutissma, no longer produces these metabolites; further biological evaluation as well as structure confirmation therefore mandated synthesis. Our longstanding interest in the construction of biologically active hemi- and spiroketals led us to undertake the first total syntheses of 1 and 2. Challenging features of the targets included the chemical sensitivity of the β-carbalkoxy hemiketal moiety and the C(10) stereocenter as well as the very considerable steric congestion of the 16-membered ring.