A Practical and Scalable-Oriented Enantioselective Synthesis of ( <i>S</i> )-Autumnaline
High Resolution Image Download MS PowerPoint Slide A process-friendly and enantioselective total synthesis of ( S )-autumnaline, a key biosynthetic precursor to the colchicine alkaloids, is reported. The strategy relies on a Bischler–Napieralski cyclization–asymmetric imine reduction sequence to construct the chiral isoquinoline core. Significant process innovations include a cyanide-free homologation using a Darzens reaction and a chromatography-free purification strategy via d -tartrate salt formation. The absolute configuration was definitively confirmed through a combination of circular dichroism (CD) spectroscopy and computational modeling. This developed process affords ( S )-autumnaline in 11 steps (nine-step longest linear sequence) with a 13% overall yield.
Authors
- Alessandro Brusa (ORCID: https://orcid.org/0000-0002-2884-2395)
- Mario Falzoni
- Armando Carlone (ORCID: https://orcid.org/0000-0003-2983-6445)
- Daniele Lanaro
- Massimiliano Aschi (ORCID: https://orcid.org/0000-0003-2959-0158)
- Pietro Allegrini (ORCID: https://orcid.org/0000-0002-4380-9577)
- Maria Luisa Gelmi (ORCID: https://orcid.org/0000-0003-0743-5499)
- Andrea Mazzanti (ORCID: https://orcid.org/0000-0003-1819-8863)
- Matteo Bottiglieri
- Andrea Gambini
- Gabriella Zappia
- Andrea Bonetti
- Federico Sala
- Francesco Feola
- Fabio Pesciaioli
- Carola Tomassi
Institutions
- United States Nuclear Regulatory Commission (US)
- University of Milan (IT)
- University of L'Aquila (IT)
- Indena (Italy) (IT)
- University of Bologna (IT)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1021/acs.oprd.5c00490
- Primary Topic
- Advanced Synthetic Organic Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00