A Novel Family of [1,4]Thiazino[2,3,4-ij]quinolin-4-ium Derivatives: Regioselective Synthesis Based on Unsaturated Heteroatom and Heterocyclic Compounds and Antibacterial Activity.

Vladimir A Potapov,Lyudmila A Belovezhets,Svetlana V Amosova,Roman S Ishigeev

doi:10.3390/molecules26185579

Abstract

A novel family of [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives was synthesized by annulation reactions of 8-quinolinesulfenyl chloride with unsaturated heteroatom and heterocyclic compounds. It was found that the reactions with 4-pentenoic and 5-hexenoic acids, allyl chloride and bromide, allyl cyanate and vinyl heterocyclic compounds (N-vinyl pyrrolidin-2-one and 1-vinylimidazole) proceeded in a regioselective mode but with the opposite regiochemistry. The reactions with vinyl heterocyclic compounds included electrophilic addition of the sulfur atom of 8-quinolinesulfenyl chloride to the β-carbon atom of the vinyl group. In the case of other substrates, the annulation proceeded with the attachment of the sulfur atom to the α-carbon atom of the vinyl group. The antibacterial activity of novel water-soluble compounds against Enterococcus durans, Bacillus subtilis and Escherichia coli was evaluated. Compounds with high antibacterial activity were found.

Highlights

Quinoline derivatives are used in the development of new drugs and exhibit a wide spectrum of biological activity [1,2,3,4,5]
Unsaturated heteroatom (4-pentenoic and 5-hexenoic acids, allyl chloride and bromide, allyl cyanate, ethyl vinyl and butyl vinyl ethers) and heterocyclic (N-vinyl pyrrolidin2-one, 1-vinylimidazole and 2,3-dihydrofuran) compounds were used for the efficient regioselective synthesis of a novel family of [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives by annulation reactions with 8-quinolinesulfenyl chloride
The reactions with 4-pentenoic and 5-hexenoic acids, allylchloride, allylbromide and allyl cyanate included the electrophilic addition of the sulfur atom of sulfenyl chloride to the α-carbon atom of the vinyl group (“anti-Markovnikov direction”), while the annulation reactions with N-vinyl pyrrolidin-2-one, 1-vinylimidazole, 2,3-dihydrofuran, ethyl vinyl and butyl vinyl ethers proceeded with the attachment of the sulfur atom to the β-carbon atom of the vinyl group (“Markovnikov direction”)

Summary

Introduction

Quinoline derivatives are used in the development of new drugs and exhibit a wide spectrum of biological activity [1,2,3,4,5]. The commonly used antibiotic rufloxacin can be considered a 2H,3H-[1,4]thiazino[2,3,4ij]quinolin-4-ium derivative (Figure 1). Despite some progress in the development of synthetic methods for the preparation of 2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives [33,34,35,36,37,38,39,40,41], the annulation reactions Dofes8p-qitueisnoomlineepsruolfgerneyssl ihnatlhideeds ewveitlhopamneunmt obfesryonfthveitnicylmicethheotedrsofaotromthecpomreppoaruantidosn (4o-fp2eHnt,e3nHo-i[c1,4a]ctihdi,az5i-nhoe[x2e,n3,o4i-cij]aqcuidin, oallilny-l4-cihulmoriddeeriavnadtivbersom[3i3d–e4,1]a,lltyhlecyanannautlea,tiNon-3vrionef ay15clptyiorrnosliodfin8--2q-uonineo, li1n-evsiunlyfleinmyildahzaolildee, setwhiytlh aandnubmubtyerl ovfinvyilnyeltihcerhse)tehraovaetomnotcobmeepnoudned-s s(c4r-ibpeedntiennothice laicteidra, tu5-rhee. By carrying out the reaction of sulfenyl chloride 3 with allylchloride and allylbromide under the same conditions as the synthesis of compounds. Synthesis of 2-(chloromethyl)- and 2-(bromomethyl)-2Н,3Н-[1,4]thiazino[2,3,4-ij]quinolin-4-ium chlorides 6 and 7 from ally6lchloride, allylbromide and sulfenyl chloride 3.

Synthesis of Compounds 4–8

Synthesis of Compounds 9–13

Conclusions