Syntheses of Amorfrutins and Derivatives via Tandem Diels-Alder and Anionic Cascade Approaches.

We describe two complementary approaches based on a convergent [4+2] logic toward the synthesis of amorfrutins, cannabinoids, and related plant metabolites. An anionic cascade cyclization employing ß-methoxycrotonates and ß-chloro-α,ß-unsaturated esters yielded amorfrutins in four linear steps and demonstrated utility of ß-alkoxycrotonate-derived nucleophiles as functional equivalents of ß-ketoester-derived dianions. Analogously, tandem Diels-Alder/retro-Diels-Alder cycloaddition of dimedone-derived bis(trimethylsiloxy)-dienes and α,ß-alkynyl ester dienophiles provided facile access to resorcinol precursors of amorfrutins and cannabinoids, avoiding late-stage installation of prenyl or geranyl moieties as in previous approaches.

Identification of Uric Acid Gluconucleoside-Ascaroside Conjugates in Caenorhabditis elegans by Combining Synthesis and MicroED.

Few nucleoside-derived natural products have been identified from animals, despite the ubiquity of nucleosides in living organisms. Here, we use a combination of synthesis and the emerging electron microscopy technique microcrystal electron diffraction to determine the structures of several N3-(ß-glucopyranosyl)uric acid derivatives in Caenorhabditis elegans. These noncanonical gluconucleosides further integrate an ascaroside moiety, for which we present a shortened synthetic route. The production of a phosphorylated gluconucleoside is influenced by evolutionarily conserved insulin signaling.