New Water-Soluble Condensed Heterocyclic Compounds with Antimicrobial Activity Based on Annulation Reactions of 8-Quinolinesulfenyl Halides with Natural Products and Alkenes

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

doi:10.3390/app11188532

Abstract

The annulation reactions of 8-quinolinesulfenyl halides with natural products and alkenes affording new water-soluble [1,4]thiazino[2,3,4-ij]quinolin-4-ium derivatives in high or quantitative yields are developed in this study. The reactions with styrene derivatives and terminal alkenes including allyl arenes proceed in a regioselective manner but with the opposite regiochemistry. The reactions with terminal alkenes including allyl arenes occur in an anti-Markovnikov fashion (regarding addition of the 8-quinolinesulfenyl electrophile to the double bond) to give 2-organyl-2H,3H-[1,4]thiazino[2,3,4-ij]quinolin-4-ium halides, while the reactions with styrene derivatives proceed in a Markovnikov fashion, leading to 3-substituted condensed heterocyclic compounds. In general, styrene derivatives demonstrate higher reactivity in the annulation reactions compared to the terminal alkenes. Antimicrobial activity of novel water-soluble compounds against Enterococcus durans, Bacillus subtilis and Escherichia coli are evaluated. The compounds with high antimicrobial activity are found. The annulation products of the reactions of 8-quinolinesulfenyl halides with 1H-indene, eugenol, methyl eugenol and 1-heptene, are superior in their activity compared to the antibiotic gentamicin.

Highlights

The quinoline skeleton occurs in many natural products, including alkaloids
All the studied substrates can be schematically divided into two groups: terminal alkenes including allyl arenes and styrene derivatives, which contain the double bond in conjugation with the benzene ring
Yields have been developed based on the annulation reactions of 8-quinolinesulfenyl halides with natural products and alkenes

Summary

Introduction

The quinoline skeleton occurs in many natural products, including alkaloids. Some containing the quinoline ring natural products have been used as lead molecules for the development of novel biologically active compounds and drugs [1,2,3,4,5]. Many modern drugs have been designed based on the quinoline scaffold. The quinoline scaffold has often been used for the design and synthesis of various synthetic compounds with pharmacological properties [1,2,3,4,5,6,7,8]. Quinoline derivatives exhibit a variety of biological activities including antibacterial, antivirus, anticancer, antifungal, antimalarial, cardiovascular, anticonvulsant, analgesic, antimycobacterial, anti-inflammatory, antihelminthic, antiprotozoal and antioxidant properties [1,2,3,4,5,6,7,8,9,10]

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Conclusion