Amphidinolides T2, T3, and T4, new 19-membered macrolides from the dinoflagellate Amphidinium sp and the biosynthesis of amphidinolide T1

Three new 19-membered macrolides, amphidinolides T2 (2), T3 (3), and T4 (4) , structurally related to amphidinolide T1 (1) have been isolated from two strains of marine dinoflagellates of the genus Amphidinium. The structures of 2-4 were elucidated on the basis of spectroscopic data. The absolute con figurations at C-7, C-8, and C-10 of 1-4 were determined by comparison of N MR data of their C-1-C-12 segments with those of synthetic model compounds for the tetrahydrofuran portion. The biosynthetic origins of amphidinolide TI (1) were investigated on the basis of C-13 NMR data of a C-13 enriched s ample obtained by feeding experiments with [1-C-13], [2-C-13], and [1,2-C-1 3(2)] sodium acetates and C-13-labeled sodium bicarbonstte in the cultures of the dinoflagellate. These incorporation patterns suggested that amphidin olide T1 (1) was generated from four successive palyketide chains, an isola ted C-1 unit formed from C-2 of acetates, and three unusual Ct units derive d only from C-2 of acetates. Furthermore, it is noted that five oxygenated carbons of C-l, C-7, C-12, C-13, and C-18 were not derived from the C-1 car bonyl, but from the C-2 methyl of acetates.