Exploring Convergent Two‐Step Synthetic Approaches to the Pancratistatin Framework. Issue 31 (18th August 2022)

• Record Type: Journal Article
• Authors: Di Iulio, Gemma A.; Mahon, Mary F.; Caggiano, Lorenzo
• Is Part Of: ChemistrySelect. Volume 7:Issue 31(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-18
• Subjects: Acylation -- Aromatic substitution -- Brønsted acid catalysis -- Nitrogen heterocycles -- Synthetic methods; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202202703
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Pancratistatin and narciclasine are natural products that display potent and selective antiproliferative activity against various cancer cells. We explore convergent synthetic routes to access the pancratistatin framework in just two steps, without the need for metal catalysis or activated substrates via a common indanone intermediate. The indanone is synthesised by intermolecular Friedel‐Crafts acylation with trifluoroacetic acid anhydride (TFAA), by two alternative routes, and then undergoes a Schmidt reaction with TFA to generate the pancratistatin core. This concise approach offers the possibility of generating various pancratistatin analogues for further development. Abstract : A convergent, two‐step approach to the Pancratistatin framework is discussed. The routes involve intermolecular Friedel‐Crafts acylation/cyclisation to generate an indanone and are achieved without the use of metal‐catalysis or activated substrates. The indanone can then undergo a Schmidt reaction to afford the lactam core present in the Amaryllidaceae family of compounds.