Harnessing <i>exo</i> -Enol Ether Glycosides: Direct Synthesis of Tricyclic Epoxybenzoxocine Cores via a Programmed Cationic Cascade
A novel acid-catalyzed cascade reaction couples <i>exo</i>-enol ether glycosides with phenols, enabling stereocontrolled, single-step synthesis of tricyclic ring systems structurally related to natural products, such as nogalamycin and serjanione A. This method leverages <i>exo</i>-glycals with two masked oxocarbenium centers for efficient bis-nucleophile coupling to build intricate architectures. Density functional theory (DFT) calculations reveal a mechanism involving three distinct oxocarbenium intermediates and elucidate the origin of the diastereoselectivity in the formation of <i>exo</i>-, <i>endo</i>-, and <i>C</i>-glycosidic bonds during the domino reaction.
Authors
- Israel Fernández (ORCID: https://orcid.org/0000-0002-0186-9774)
- Damien Hazelard (ORCID: https://orcid.org/0000-0003-1046-4266)
- Philippe Compain (ORCID: https://orcid.org/0000-0002-6877-0859)
- Pierre Lafargue
- Roman Fischbach (ORCID: https://orcid.org/0000-0002-2125-6748)
- Daniel González‐Pinardo (ORCID: https://orcid.org/0009-0002-1151-2872)
- Mathieu Pascaretti
- Yanis Rieder
- Matisse Da Silveira
- Charlie Triballeau
Institutions
- Universidad Complutense de Madrid (ES)
- Centre National de la Recherche Scientifique (FR)
- Laboratoire de Chémo-biologie synthétique et thérapeutique (FR)
- Laboratoire de Chimie Moléculaire (FR)
- Instituto de Química Orgánica General (ES)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-11-03
- DOI
- https://doi.org/10.1021/acs.orglett.5c04017
- Primary Topic
- Carbohydrate Chemistry and Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00