ChemInform Abstract: Total Syntheses of Ningalin A (V), Lamellarin O (VI), Lukianol A (VII), and Permethyl Storniamide A (VIII) Utilizing Heterocyclic Azadiene Diels—Alder Reactions.

✍ Scribed by Dale L. Boger; Christopher W. Boyce; Marc A. Labroli; Clark A. Sehon; Qing Jin

• Publisher: John Wiley and Sons
• Year: 2010
• Weight: 35 KB
• Volume: 30
• Category: Article
• ISSN: 0931-7597
• DOI: 10.1002/chin.199922242

✦ Synopsis

Total Syntheses of Ningalin A (V), Lamellarin O (VI), Lukianol A (VII), and Permethyl Storniamide A (VIII) Utilizing Heterocyclic Azadiene Diels-Alder Reactions.

-Efficient total syntheses of the title compounds (V)-(VIII) are presented including a heterocyclic azadiene Diels-Alder reaction and subsequent ring contraction as key steps. Thus, symmetrical diarylacetylenes (I), prepared by palladium-catalyzed or Stille coupling, react with electron-deficient tetrazine (II) in refluxing toluene to furnish diazine derivatives (III). Due to the oxygenated aryl substituents, the reactivity of acetylenes (I) is increased allowing for isolation of the diazines (III) in good yields. Diazines undergo ring contraction in the system Zn-AcOH to give 2,5-dicarboxylated pyrroles (IV). Compounds (V)-(VIII) as well as their precursors are tested for their biological activity. While compound (VI) possesses good cytotoxic activity, compound (VIII) indicates a resensitizing of multidrug-resistant tumor cell lines to antitumor agents like doxorubicin. -