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

Abstract

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.

Marine natural products

“…305 The relative conguration of the C-3-C-12 portion of amphirionin-5 716 was assigned by stereodivergent synthesis of six diastereomeric model compounds and comparison of their NMR spectroscopic data with those reported for the natural product. 306,307 The results of stereoselective and stereodivergent synthesis of the proposed C-79-C-104 fragment of symbiodinolide and stereodivergent syntheses of the C-79-C-97 and C-94-C-104 fragments have led to the reassignement of the relative conguration of this portion of 717. 308,309 The complete biosynthetic pathway to the polyketide 13-desmethylspirolide C in Alexandrium ostenfeldii has been established by feeding experiments with 13 C methyllabelled methionine and application of the odd-even methylation rule.…”

Structure and Stereochemistry of Amphidinolide N Congeners from Marine Dinoflagellate <i>Amphidinium</i> Species

“…The crude fraction, which exhibited >90% cell-growth inhibition of human cervix adenocarcinoma HeLa cells at 1 µg/mL, was chromatographed by octadecylsilyl (ODS) and amino silica gel column chromatography and then ODS HPLC to afford isocaribenolide-I (1, 0.006% from dry weight) together with iriomoteolides-10a, 12a, 25) and 13a 24) and amphirionin-5. 26,27) The Amphidinium KCA09056 strain was separated from the surface of the seagrass collected off Iriomote Island. 28) The toluene-soluble materials of the microalgal extract were subjected to silica gel column chromatography, and then the crude fraction showing potent cytotoxic activity was chromatographed using an ODS column and then ODS HPLC to afford two cytotoxic components, compounds 2 (0.0054%) and 3 (0.0024%).…”

Pitfalls in the structural elucidation of small molecules. A critical analysis of a decade of structural misassignments of marine natural products

“…29). 186,187 However, the absolute conguration of polyketide amphirionin-5 remained unknown. For polyketides, a stereochemical prediction is, in principle, possible on the basis of a biosynthetic gene cluster analysis of the ketoreductase and enoylreductase domains containing hydroxyl and methyl stereocenters.…”