Total Synthesis of (R)-Argentilactone and (R)-Goniothalamin Using a Free-Radical Photoredox Approach to α,β-Unsaturated δ-Lactones

Abstract

α,β-Unsaturated δ-lactones are structural motifs found in diverse pharmacologically active natural products. In fact, the unsaturated lactone is often responsible for the biological activity. Herein, we report a new approach for the syntheses of (R)-argentilactone and (R)-goniothalamin based on a photoredox intermolecular iodolactonization mediated by a photoredox process. This new approach, already employed in our research group, stands as a new methodology to achieve several natural products containing α,β-unsaturated δ-lactones.

Total Synthesis and Structure Confirmation of (−)-Asimitrin, a C37 Annonaceous Acetogenin with a Hydroxylated Adjacent Bis-Tetrahydrofuran Core

“…Most importantly, the key 17-hydroxy-16,17- erythro -16,19- trans -THF intermediate 6 should be accessible by subjecting 16,17- erythro ω -bromo α-alkoxy amide 7 to our stereoselective chelate-controlled IAEA reaction . Finally, we reasoned that IAEA substrate 7 could be obtained in a straightforward manner from the 16,17- erythro epoxy alcohol 8 , which could be derived from known (16 R )-allylic alcohol 9 via Sharpless asymmetric epoxidation (SAE) …”

“…Our asymmetric synthesis of (−)-asimitrin ( 1 ) commenced with the construction of key 17-hydroxy-16,17- erythro -16,19- trans -THF 6 (Scheme ). Thus, known allylic alcohol 9 , prepared from commercially available ( S )-glycidol in two steps, was subjected to the SAE reaction to deliver the desired 16,17- erythro epoxy alcohol 8 in 85% yield as a single diastereomer. Williamson O -alkylation of 8 with N , N -dimethyl bromoacetamide then gave rise to epoxy α-alkoxy amide 10 , which underwent regioselective opening by ( n- Bu) 4 NBr in the presence of Mg­(NO 3 ) 2 ·6H 2 O to afford bromo amide 11 in an excellent 94% overall yield (two steps).…”