THE SYNTHESIS OF ALISAMYCIN, NISAMYCIN, LL-C10037-ALPHA AND NOVEL EPOXYQUINOL AND EPOXYQUINONE ANALOGS OF MANUMYCIN-A

Versatile synthetic routes are described for the preparation of a rang e of epoxyquinol and epoxyquinone analogues of the antitumour antibiot ic manumycin A lacking the lower side chain, and these procedures have also been applied to prepare the bioactive natural product LL-C 10037 alpha. The extension of this methodology to provide a general synthet ic route to the manumycin family of antibiotics is discussed and exemp lified by the first total synthesis of alisamycin and ent-alisamycin. This route includes the novel, stereoselective organometallic addition of the Corey-Wollenberg reagent (E-2-tributylstannylethenyllithium) t o the manumycin nucleus and palladium catalysed Stille coupling techno logy for the introduction of the polyunsaturated 2-amino-3-hydroxycycl opentenone derived amide. Similar methodology has also been employed t o complete the first total synthesis of the antibiotic nisamycin.