A three-component reaction for rapid access to underexplored 1,3-thiazine-2-thiones

Abstract

Driven by the shortage of known effective possibilities for the synthesis of 4-hydroxy-3,4-dihydro-2H-1,3-thiazine-2-thiones on the one hand and the promising potential of these structures as novel drug candidates on the other hand, synthetic access to 4-hydroxy-3,4-dihydro-2H-1,3-thiazine-2-thiones was developed. The desired products could be synthesized effectively and facilely starting from β-chlorovinyl aldehydes with the aid of a new MCR (multicomponent reaction). Furthermore, the 4-hydroxy-3,4-dihydro-2H-1,3-thiazine-2-thiones are shown to be appropriate substrates in the preparation of diverse annulated polycyclic systems.

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

“…Our interest in the preparation of structurally diverse heterosteroids lead to a need for a facile flexible strategy, in which a common intermediate can be used in a conjunctive fashion to form an array of N -heterocycles attached or fused to the steroid core. Hence, we turned to β-chlorovinyl aldehydes, which are readily available by the Vilsmeier–Haack reaction (Tasneem, 2003 ) and proved to be highly reactive ambident electrophiles (Bera et al, 2008 ; Bezboruah et al, 2013 ; Brockmeyer et al, 2014 ; Kroger et al, 2015 ). Recently, we have reported the synthesis of steroidal pyridazines (Komkov et al, 2015 ; Volkova et al, 2016 ), thiadiazoles (Zavarzin et al, 2013 ), and 4,5-disubstituted pyrimidines (Komendantova et al, 2017 ) via condensation of β-chlorovinyl aldehydes with bis-nucleophiles such as oxamic acid thiohydrazides and amidines.…”

Aldo‐X Bifunctional Building Blocks for the Synthesis of Heterocycles

“…The other β‐aldo‐halides have also been sporadically used in the synthesis of heterocyclic compounds. For example, a β‐chlorovinyl aldehyde 148 has been used in the synthesis of 4‐hydroxy‐3,4‐dihydro‐2H‐1,3‐thiazine‐2‐thione 149 through a three‐component reaction with an aliphatic amine and carbon disulfide (Scheme ) . The use of tryptamine derivatives as amine components leads to a cascade consisting of the formation of 2 H ‐1,3‐thiazine‐2‐thione and a Pictet–Spengler‐type cyclization.…”

Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel (4‐Hydroxy‐2‐Thioxo‐3,4‐Dihydro‐2H‐[1,3]Thiazin‐6‐Yl)‐Chromen‐2‐Ones via a Multicomponent Approach

“…A survey of the literature revealed that a few inefficient methods for the synthesis of 1,3‐thiazine‐2‐thiones have been reported . Very recently, Kroger et al, reported the synthesis of 4‐hydroxy‐3,4‐dihydro‐2 H ‐1,3‐thiazine‐2‐thiones through a multicomponent approach. However, considering the pharmacological potential and the lack of efficient methods for the synthesis of 1,3‐thiazin‐2‐thiones, there is still a need to develop efficient routes for the synthesis of this class of important molecules.…”