Enigmazole Phosphomacrolides from the Marine Sponge Cinachyrella enigmatica .

Enigmazole B ( 1 ) and four new analogues, cis -enigmazole B ( 2 ), dehydroenigmazole B ( 3 ), enigmimide B ( 4 ), and enigmimide A ( 5 ), were isolated from the marine sponge Cinachyrella enigmatica . Their planar structures were elucidated by detailed NMR and MS data analyses, which established 1 - 3 to be oxazole-substituted 18-membered phosphomacrolides, while 4 and 5 were oxazole ring-opened congeners. The relative and absolute configurations in 1 were determined by a combination of chemical transformations and spectroscopic analyses. Photooxidation of the oxazole moiety in 1 gave enigmimide B ( 4 ), thus establishing that 4 has the same absolute configuration of 1 . Enigmazole B ( 1 ) along with analogues 2 and 3 showed cytotoxicity against murine IC-2 mast cells with IC 50 values of 3.6-7.0 μM. The enigmimides ( 4 and 5 ) and dephosphoenigmazoles did not show cytotoxicity (IC 50 > 10 μM), implying that both the oxazole moiety and the phosphate group are necessary for the cytotoxicity of the enigmazole class macrolides.