Okinawan marine dinoflagellate Amphidinium sp. contains series of cytotoxic macrolides, named amphidinolide. Two novel 15-membered macrolides, amphidinolides O (1) and P (2), which contains cytotoxicity against murine lymphoma L1210 and human epidermoid carcinoma KB cells in vitro (IC50 values: 1, 1.7 and 3.6 mg/ml, respectively; 2, 1.6 and 5.8 mg/ml, respectively).
Structures of amphidinolide O and P were related closely; 1 and 2 have seven chiral centers, epoxide, an internal double-bond, two exo-methylenes (C-5, C-16). The C-11 ketone of compound 1 is replaced by an exo-methylene group in compound 2.
From the structural similarity, we planned a convergent strategy for the completion of 1 and 2 via compound 3 and 4; protected hydroxide at C-11. This strategy could be total synthesis of two natural products 1 and 2 in the same process.