Biomimetic Total Synthesis of (±)‐Verrubenzospirolactone

• Published in: Angewandte Chemie International Edition Vol. 56; no. 29; pp. 8532 - 8535
• Main Authors: Lam, Hiu C., Pepper, Henry P., Sumby, Christopher J., George, Jonathan H.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 10.07.2017; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: biomimetic synthesis; Biomimetics; Cascade chemical reactions; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; cycloaddition; natural products; Physical Sciences; Science & Technology; terpenoids; total synthesis; natural products; ORGANIC-SYNTHESIS; METABOLITES; cycloaddition; terpenoids; TRIDACHIAHYDROPYRONES; total synthesis; biomimetic synthesis; WATER
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201700114

A five‐step total synthesis of (±)‐verrubenzospirolactone has been achieved using a biomimetic, intramolecular Diels–Alder reaction of a 2H‐chromene to form two rings and four stereocenters in the final step. This Diels–Alder reaction occurs spontaneously at 30 °C “on‐water”, and thus suggests that it is likely to be non‐enzymatic in nature. The structure of (±)‐verrubenzospirolactone was also used to inspire a quadruple cascade reaction to generate seven stereocenters, four rings, three C−C bonds, and two C−O bonds in one step. High five: A five‐step total synthesis of (±)‐verrubenzospirolactone (1) has been achieved using a biomimetic, intramolecular Diels–Alder reaction of a 2H‐chromene to form two rings and four stereocenters in the final step. This Diels–Alder reaction occurs spontaneously at 30 °C “on‐water”, thus suggesting that it is likely to be non‐enzymatic in nature.