Stereodivergent Synthesis and Configurational Assignment of the C1–C15 Segment of Amphirionin‑5

The relative configuration of the C3–C12 portion of amphirionin-5, a novel marine polyketide with potent cell proliferation-promoting activity, was established by the stereodivergent synthesis of six diastereomeric model compounds and comparison of their NMR spectroscopic data with those reported for the natural product. This study led to the elucidation of the relative configuration between C4/C5 and C9/C12 and to the reassignment of the proposed configuration of the C9 position of amphirionin-5

Direct and Stereospecific Interaction of Amphidinol 3 with Sterol in Lipid Bilayers

Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate Amphidinium klebsii, possesses potent antifungal activity. Although AM3 permeabilizes phospholipid membranes only in the presence of sterol, the detailed molecular basis by which AM3 recognizes sterols in membranes remains unknown. Here, we investigated the molecular interaction between sterols and AM3 in membranes from the viewpoint of stereospecific molecular recognition using ergosterol, cholesterol, and epicholesterol, which is the 3-OH epimer of cholesterol. Dye leakage assays, surface plasmon resonance experiments, ²H and ³¹P NMR measurements, and microscopic observations revealed that AM3 directly interacts with membrane sterols through the strict molecular recognition of the stereochemistry of the sterol 3-OH group. The direct interaction enhances the membrane binding efficiency of AM3, which subsequently permeabilizes membranes without altering membrane integrity

Amphirionin‑4 with Potent Proliferation-Promoting Activity on Bone Marrow Stromal Cells from a Marine Dinoflagellate <i>Amphidinium</i> Species

A linear polyketide, amphirionin-4 (<b>1</b>), has been isolated from cultivated algal cells of the marine dinoflagellate <i>Amphidinium</i> species. The structure was elucidated on the basis of detailed analyses of 1D and 2D NMR data, and the absolute configurations of C-4 and C-8 were determined using the modified Mosher’s method. Amphirionin-4 (<b>1</b>) exhibited extremely potent proliferation-promoting activity on murine bone marrow stromal ST-2 cells (950% promotion) at a concentration of 0.1 ng/mL