Synthesis of 5-Functionalized 1-(Hetero)Aryl-1,2-thiazine 1-Oxides through a CSIC Reaction Strategy
Abstract Herein, we report an efficient strategy for the synthesis of C5-functionalized 1-(hetero)aryl-1,2-thiazine 1-oxides (i.e., C5-functionalized six-membered endocyclic sulfoximines) based on the carbanion-mediated sulfonate (or sulfonamide) intermolecular coupling and intramolecular cyclization (CSIC) reaction. The starting compounds are readily available 2,2-disubstituted 3-bromopropanenitriles and imino(methyl)(hetero/aryl)-λ6-sulfanones, and the reaction is performed in a one-pot fashion. The method works well and provides previously unreported spirocyclic and S-heteroaryl-substituted 1,2-thiazine 1-oxides. These compounds are designed as multi-target small molecules and a preliminary in silico study indicates their good binding affinity to CLK4 and MAO B – the receptors associated with cancer and neurodegenerative diseases.
Authors
- Alexey V. Dobrydnev (ORCID: https://orcid.org/0000-0001-7628-0465)
- Yaroslav O. Chuchvera (ORCID: https://orcid.org/0009-0001-8584-8793)
- Yulian M. Volovenko (ORCID: https://orcid.org/0000-0003-4321-1484)
- Eugeniy N. Ostapchuk (ORCID: https://orcid.org/0000-0003-2441-9255)
- Maria V. Popova (ORCID: https://orcid.org/0000-0003-2886-9683)
- Oleksandr P. Korobka
- Yurii O. Horbatochkin
Institutions
- National Academy of Sciences of Ukraine (UA)
- Taras Shevchenko National University of Kyiv (UA)
- Max Planck Institute for Polymer Research (DE)
- State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine (UA)
- Institute of Organic Chemistry (UA)
- Enamine (Ukraine) (UA)
- V. N. Karazin Kharkiv National University (UA)
Publication Details
- Journal
- Synlett
- Published
- 2025-05-07
- DOI
- https://doi.org/10.1055/a-2602-6899
- Primary Topic
- Phenothiazines and Benzothiazines Synthesis and Activities
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Education and Science of Ukraine
- Enamine