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An Ugi-Joullié Platform for Medicinally Relevant 1,4-Dihydrobenzothiazines.

Created on 04 Jul 2026

Authors

Xiaofang Lei, Christina Tomza, Maria-Aikaterini Giannakaki, Maria Gkountouva, Ioannis Olbasalis, Rafaela Maria Giappa, Constantinos C Stoumpos, Christos Kontogiorgis, Alexander Dömling, Constantinos G Neochoritis

Published in

ChemMedChem. Volume 21. Issue 13. Pages e70368. Jul 14, 2026.

Abstract

A concise and modular synthetic platform for the rapid assembly of functionalized 1,4-dihydrobenzothiazines is reported through an Ugi-Joullié two-component reaction of a preformed benzothiazine-derived imine with diverse isocyanides. The methodology proceeds under mild, operationally simple conditions and exhibits broad isocyanide scope, accommodating aryl, benzylic, aliphatic, and heterocyclic substituents to furnish a 19-member library of benzothiazines in 51%-96% yields. The reaction demonstrates high functional-group tolerance and scalability to the millimole level, enabling efficient access to structurally diverse benzothiazine derivatives relevant for medicinal chemistry exploration. Single-crystal X-ray diffraction analyses revealed characteristic conformational features of the scaffold, including a twisted-boat geometry and a Z-oriented arrangement of the two NH groups. In addition, late-stage oxidation of the sulfur atom to the corresponding sulfone was readily achieved in high yield, highlighting the versatility of the scaffold for post-assembly diversification. Preliminary antimicrobial evaluation against a panel of Gram-positive and Gram-negative bacterial strains revealed strain-dependent antibacterial activity for selected derivatives, supporting the suitability of the benzothiazine framework for further medicinal chemistry optimization.

PMID:
42399699
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.

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